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Citrome L. Interpreting and applying the EUFEST results using number needed to treat: antipsychotic effectiveness in first-episode schizophrenia. Int J Clin Pract. 2008 May ; 62(5):837-40. Pubmed Abstract
Citrome L. Interpreting and applying the EUFEST results using number needed to treat: antipsychotic effectiveness in first-episode schizophrenia. Int J Clin Pract. 2008 May ; 62(5):837-40. Pubmed Abstract
The EUFEST study found that haloperidol, in comparison with several SGAs, was associated with a higher rate of overall treatment discontinuation, a higher rate of discontinuation because of lack of efficacy, a higher rate of discontinuation because of side effects, and worse outcome on the CGI and the GAF. Surprisingly, the authors last sentence reads: It cannot be concluded that SGAs are more efficacious than is haloperidol . Although restraint in scientific conclusions is generally admirable, I think that these authors are being too conservative in the interpretation of their important findings.
The reason for their hesitancy, it appears, is that the PANSS and the rehospitalization rates have not shown significant differences among drugs. Furthermore, they are concerned about the possibility of provider expectation biasing the results against haloperidol: if the psychiatrists expected haloperidol to do poorly, perhaps they were more likely to discontinue it than another treatment in which they believed. But the lack of difference on the PANSS total can have many reasons. Subanalyses of PANSS factors and data on rater training effectiveness that may be published in secondary studies could shed some light on this. Rehospitalization rates would be expected to depend on the treatment the patients received after their participation in the study was terminated; this topic is also likely to be explored later.
Provider expectations are difficult to demonstrate. The authors polled the site coordinators, asking them whether they expected haloperidol to lead to the worst outcome, or whether the outcome would be similar to that with SGAs. The authors then tested the hypothesis that the sites where haloperidol was expected to do worse would have higher discontinuation rates with haloperidol than the other sites. They found a non-significant difference in the expected direction. It should be noted that the poll occurred after the end of data collection, and that the coordinators were not blinded to the treatment assignments. Therefore, the result of the poll could have reflected experience as well as expectation.
Is it possible that the differences between haloperidol and the SGAs on CGI and GAF (but not on the PANSS) were due to their greater vulnerability to bias of these two scales than the PANSS? There are two speculations here: one, that a bias existed in this study, and two, that the scales have inherent differences in their liability to rater bias. No empirical evidence supports either of these speculations.
In summary, the EUFEST study results, based on data from close to 500 patients collected by dozens of investigators, permit more definitive conclusions than the authors have drawn in their first paper. We are looking forward to follow-up articles by this outstanding group of investigators. Practicing psychiatrists will particularly appreciate a presentation of the clinical implications of this landmark study.
View all comments by Jan Volavka
Related News: Study Questions Advantages of Newer Antipsychotics for Early Schizophrenia
Comment by: Peter F. Buckley
Submitted 11 April 2008
Posted 11 April 2008
This timely study, conducted by a stellar group of European investigators, adds to the continued debate about choice of medications for schizophrenia, informed by other similarly impressive pragmatic trials such as CATIE and CUTlass. Unlike the other recently published first-episode treatment study—the CAFE study (McEvoy et al., 2007)—which was double blind and compared SGAs only (risperidone versus olanzapine versus quetiapine), EUFEST better fits the model of a pragmatic trial and also included a FGA comparator. Although readers, particularly policy makers, will inevitably be drawn to the Should I choose an FGA or SGA content of this study, it seems to me that the most striking finding is (yet again) how frequently patients stop their medications. The 72 percent overall All Cause Discontinuation rate bears an uncanny resemblance to the 74 percent in CATIE and to the similar rate in the one-year CAFE first-episode study. Thus, medication non-adherence is a major treatment issue right from the onset of treatment. Set in that light, the differences observed in the study between agents are relatively modest. The data do not endorse the preferential lead off with any particular agent. Indeed, much like the discussion that followed the publication of the CATIE study, these data make the case for wide availability and choice of antipsychotic medications, rather than confining to a selective FGA first or X drug before trying Y among the SGAs. I agree with Dr Volavka's comment that subsequent analyses of these valuable data may bring additional insights to the surface.
McEvoy JP, Lieberman JA, Perkins DO, Hamer RM, Gu H, Lazarus A, Sweitzer D, Olexy C, Weiden P, Strakowski SD. Efficacy and tolerability of olanzapine, quetiapine, and risperidone in the treatment of early psychosis: a randomized, double-blind 52-week comparison. Am J Psychiatry. 2007 Jul ;164(7):1050-60. Abstract
View all comments by Peter F. Buckley
Related News: Study Questions Advantages of Newer Antipsychotics for Early Schizophrenia
Comment by: Leslie Citrome
Submitted 18 April 2008
Posted 19 April 2008
I recommend the Primary Papers
Although in EUFEST, psychopathology improved to a similar extent among the different groups, durability of the medication was quite different. This is of the utmost importance when it comes to treating patients—no one would disagree that continuation on medication is crucial in the successful treatment of patients with schizophrenia. If my goal is to pick the antipsychotic that my first-episode patient will stick with the longest, olanzapine or amisulpride appears to be what the data recommend. The alternative is to prescribe something else and then switch if necessary. Curiously, amisulpride and olanzapine (and risperidone) appeared to perform better than haloperidol in the Davis meta-analysis published when EUFEST was being launched (Davis et al., 2003).
As an exercise in looking at EUFEST through the lens of evidence-based medicine, I calculated the number needed to treat (NNT) for all-cause discontinuation (Citrome, 2008). NNT yields statistically significant pair-wise advantages for olanzapine vs. haloperidol and quetiapine; amisulpride vs. haloperidol and quetiapine; and ziprasidone vs. haloperidol. The strongest effect sizes were olanzapine or amisulpride vs. haloperidol with an NNT of four, meaning for every four patients randomized to olanzapine or amisulpride instead of haloperidol, one additional patient on olanzapine or amisulpride completed the study on his or her initially assigned medication. Overall, the EUFEST NNT results for all-cause discontinuation are consistent with what has been observed in an NNT analysis of the CATIE data (Citrome et al., 2006).
Citrome L: Interpreting and applying the EUFEST results using number needed to treat: antipsychotic effectiveness in first-episode schizophrenia. International Journal of Clinical Practice. 2008;62(5):837-840. Abstract
Citrome L, Stroup TS: Schizophrenia, Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and number needed to treat: how can CATIE inform clinicians? International Journal of Clinical Practice. 2006;60(8):933-940. Abstract
Davis JM, Chen N, Glick ID. A meta-analysis of the efficacy of second-generation antipsychotics. Arch Gen Psychiatry. 2003; 60: 55364. Abstract
View all comments by Leslie Citrome
Related News: Study Questions Advantages of Newer Antipsychotics for Early Schizophrenia
Comment by: Herbert Meltzer (Disclosure)
Submitted 29 April 2008
Posted 29 April 2008
EUFEST, CATIE, and CUtLASS: Should Atypical Antipsychotic Drugs Remain the Most Prescribed Treatment for Schizophrenia?
The EUFEST (Kahn et al., 2008) study is the third major effectiveness-style study published in the last three years whose goal has been to compare typical and atypical antipsychotic drugs in the treatment of specified subgroups of patients with schizophrenia, the others being CATIE (Lieberman et al., 2005) and CUtLASS (Jones et al., 2006). The authors of EUFEST close their report with: "It cannot be concluded that second-generation antipsychotic drugs are more efficacious than is haloperidol in the treatment of these (first-episode schizophrenia) patients," despite the fact that the discontinuation rate was the primary endpoint, and there was a significantly lower rate of discontinuation of the atypical drugs: 40 percent for amisulpride, 33 percent for olanzapine, 53 percent for quetiapine, and 45 percent for ziprasidone, vs. 72 percent for haloperidol; p <0.0001). However cautious this statement, it was still not acceptable to Robert Rosenheck (2008) who, in the accompanying Lancet commentary, states: "There clearly seems to be much less, if any [my emphasis] ground for enthusiasm about these costly drugs now than in 2002, precisely because of the finding of large, independent double-blind trials, by which he refers to the CATIE (Lieberman et al., 2005) and CUtLASS (Jones et al., 2006) studies. The EUFEST authors chose to downplay their primary outcome measure, which was robustly achieved, because rating scale changes were not significantly different between the atypical antipsychotic drugs and haloperidol and because CATIE and CUtLASS had reached similar conclusions with regard to more chronically ill patients.
As I will show, the disconnect between continuation with therapy and equivalence of changes in psychopathology confirmed what we had found more than a decade ago in a randomized, blinded, small N trial comparing clozapine and typical antipsychotic drugs in recent onset patients with schizophrenia who had a history of good response to typical antipsychotic drug treatment (Lee et al., 1994; 1999). The EUFEST articles ducked the more pressing question of which type of medication should be administered to first episode patients if, indeed, it cannot be concluded that one is more effective than another.
What in the "real world" is going on? Efficacy, effectiveness and hybrid studies
It is important to consider whether the EUFEST, CATIE, and CUtLASS studies should be considered hybrid rather than effectiveness studies, because these studies urge greater significance be paid to them than to efficacy studies. They are supposedly "real world," while claiming efficacy studies are much less so, or not at all. As pointed out by Hogarty et al. (1997), studies such as EUFEST, CATIE, and CUtLASS are much closer to what is generally called a hybrid than a true effectiveness study, because of the elaborate and extensive research apparatus they employ, making it highly likely that usual clinical practice, patient behavior, and outcome were influenced by protocol design and execution, just as they are in efficacy studies. For example, the CATIE study design most certainly encouraged switching drugs within its large-scale Phase 1 component comparing perphenazine with atypical antipsychotics, and did so in a variety of ways (Meltzer and Bobo, 2006). In addition, the CATIE study design did the same in the treatment failure phase of the study by comparing unblinded clozapine with blinded comparators and using time to discontinuation as the primary endpoint. Unblinding clozapine clearly favored it since the small proportion of eligible patients who entered that phase of the study were mainly those who wanted to receive a trial of clozapine in the first place. (McEvoy et al., 2006). Kenneth Wells, a distinguished authority on the issue of effectiveness and hybrid studies concluded, and I concur: "We do not yet know whether the findings of such hybrid studies will be clinically and socially useful" (Wells, 1999). Until we do so, it would seem prudent to withstand the pressure to make the atypical antipsychotic drugs second line treatments, which has been the explicit message from some of the authors of CATIE and CUtLASS, if not EUFEST.
Clozapine and expectations for superiority of other atypical antipsychotic drugs
Consideration of the issue of whether atypical antipsychotic drugs have advantages over typical antipsychotic drugs, the driving force behind these three hybrid studies, can begin with a consideration of whether even clozapine has advantages with regard to efficacy and time to discontinuation over typical antipsychotic drugs. Though the typical and atypical antipsychotic drugs, e.g., clozapine, olanzapine, quetiapine, risperidone, ziprasidone, and aripiprazole, are referred to in all three studies as first- and second-generation antipsychotic drugs, I prefer to refer to them as typical and atypical, as they were originally called, and as they are almost universally referred to by preclinical scientists. Labeling them as "first- and second-generation" drugs is inaccurate with regard to the time frame in which clozapine, the first of the atypical antipsychotic drugs, was initially discovered and developed (which was at the same time, or even prior to, many of the so-called first-generation drugs) and contrasts it mechanistically from the typical antipsychotic drugs.
Clozapine was labeled atypical shortly after its discovery by both preclinical and clinical investigators, solely because of its lack of extrapyramidal effects (EPS) in both laboratory animals and patients. This critical advantage is due to major differences in its pharmacology, one which is shared by all of the currently marketed atypical antipsychotic drugs developed since clozapine, with the exception of sulpiride and amisulpride. The critically important shared pharmacology of the clozapine-like atypical antipsychotic drugs—olanzapine, quetiapine, risperidone, and ziprasidone—is more potent blockade of serotonin (5-HT) 2A than dopamine (DA) D2 receptors, at optimal clinical doses (Meltzer et al.,1989; 2003). Aripiprazole substitutes partial D2 receptor agonism for relatively weaker D2 antagonism but retains the 5-HT2A antagonism common to the other atypical antipsychotics other than sulpiride and amisulpride. The so-called "fast-off" hypothesis of Kapur and Seeman (2000) to explain atypicality in antipsychotic drugs is valid only for clozapine itself and quetiapine, both of which have low affinities for the D2 receptor, but not for asenapine, olanzapine, risperidone, sertindole, and ziprasidone, which have high affinities for the D2 receptor. How important fast dissociation is for even clozapine and quetiapine is unknown.
The pharmacology of sulpiride and amisulpride, which had a decisive influence in the CUtLASS study and has never been differentiated to my knowledge, involves highly selective and potent D2 and D3 receptor blockade (Caley and Weber, 1995; Scatton et al., 1997; NIMH Psychopharmacology Drug Screening Program website), yet sulpiride was the most extensively prescribed (showing clinician insight?) of the "first-generation" drugs (49 percent of patients in that arm), while amisulpride accounted for 12 percent of the atypical drugs in the "second-generation arm" in the CUtLASS study. Both drugs, while not free of EPS, meet the definition for atypicality (Rao et al., 1981; Gerlach, 1991) and have been so identified in important meta-analyses (see Rummel et al., 2003; Leucht, 2004). Regardless of whether one believes them to be typical or atypical, it would have been prudent for the CUtLASS investigators to exclude both agents rather than risk compromising the study, as I believe they did. Their inclusion is sufficient by itself to invalidate CUtLASS in my opinion, but there were at least two other major problems that affect the validity of that study. Thus, significantly greater proportions of patients who had failed prior antipsychotic drug treatments were randomized to the atypical arm—to receive either 5-HT2A/D2 antagonists or amisulpride—than to the sulpiride plus typical antipsychotic drug arm, a major flaw which was not only not corrected for, but was not mentioned anywhere in the article to my knowledge. Next, the use of long-acting medications, with their potential for better compliance, was permitted in the patients in the typical antipsychotic arm, further biasing the results for that group of agents, while there was no use of long-acting risperidone in the atypical arm. Thus, three major biases, all favoring the typical agents, were operative in the CUtLASS study. The atypicals hardly had a chance to do well, competing against themselves, with more treatment-resistant patients assigned to that group, and utilizing only oral medications.
Clozapine, for more than a decade beginning in 1975, was rejected for all but research and compassionate need purposes, because it caused a higher rate of agranulocytosis than the typical antipsychotics. We now know this occurs approximately 30 times more frequently with clozapine (~7.5/1000 vs. 0.25/1000). The US Clozapine Multicenter Trial, of which I was an author, found that clozapine was more effective than chlorpromazine for poor-outcome, treatment-resistant patients with schizophrenia (Kane et al., 1988). The conclusions of that study have been supported by many other studies, including CATIE, CUtLASS, and a recent study of treatment-resistant first-episode patients (Agid et al., 2007). Subsequent studies from my laboratory and others showed additional benefits for clozapine over other antipsychotic drugs for cognition and suicide in non-treatment-resistant as well as treatment-resistant patients (Hagger et al., 1993; Meltzer and McGurk, 1999; Woodward et al., 2005; 2007; Meltzer and Okayli, 1995; Meltzer et al., 2003), as well as quality of life (Meltzer et al., 1993). These studies included the type of patients in the CATIE and CUtLASS study. The result of the body of research from many laboratories all over the world establishing clozapine as the "gold standard" for treating schizophrenia was that the bar was set very high for the inevitable attempts to develop drugs with the efficacy of clozapine, but without its spectrum of serious, sometimes fatal side effects, which discouraged many patients and clinicians from even trying it then and now. There are, today, no more than 60,000-90,000 of the two million patients with schizophrenia who are receiving clozapine in the U.S.
Atypical antipsychotic drugs with pharmacology similar to clozapine
Publication of the serotonin-dopamine ratio hypothesis (Meltzer et al., 1989) introduced a simple means to identify drugs other than clozapine which had a low EPS potential and facilitated the development not only of aripiprazole, olanzapine, quetiapine, risperidone and ziprasidone, which are currently marketed, but also asenapine, iloperidone, laurasidone, perospirone, and sertindole (none of which are consistent with the "fast off" hypothesis), which are in advanced stages of development in the U.S., or already marketed in other countries. In addition, a host of other novel chemical structures with preclinical characteristics of atypical antipsychotic drugs consistent with the serotonin-dopamine ratio hypothesis have been reported on. The similarity of the pharmacologic profile of the marketed agents with that of clozapine may have contributed to the expectation that all drugs which had this pharmacologic profile would be superior to typical neuroleptics in all patients with schizophrenia (Lewis and Lieberman, 2008). The publication of a pivotal large, international study comparing risperidone with haloperidol and placebo, which did find some doses of risperidone to be superior to haloperidol, although only marginally so (Marder and Meibach,1994), was a likely contributor to this expectation. However, as pointed out by the authors in an accompanying editorial (Kane, 1994), it should have been noted that many of the patients in that study were possibly treatment-resistant. It is noteworthy that risperidone at a dose of 20 mg/day was one of the two risperidone doses that were reported to be more effective than haloperidol. This high dose might be expected to be more effective than haloperidol in treatment-resistant patients (see below).
The pivotal industry studies for quetiapine and ziprasidone did not claim superiority to haloperidol, except slightly greater benefits for negative symptoms, while those for olanzapine were mixed in this regard. The major pivotal study for olanzapine, as well as the overview of its pivotal trials, claimed no advantage of olanzapine over haloperidol for improvement in total psychopathology or positive symptoms (Beasley et al., 1996; Beasley et al., 1997). However, a multicenter trial conducted in countries outside the U.S. did find olanzapine superior to haloperidol (Tollefson et al., 1997). Geddes et al. (2000) provided the first meta-analysis comparing efficacy and tolerability of typical and atypical antipsychotic drugs and found no difference in efficacy between them, but fewer EPS with atypicals. Ironically, it was two academic-based meta-analytic reviews (Davis et al., 2003; Leucht et al., 2000), which concluded that the atypicals were superior to the typical agents in efficacy, that are frequently cited as the basis for the claim that the atypical agents are superior for the non-treatment-resistant patient. In a subsequent article, Davis et al. (2008) reported that the CATIE results were consistent with the Davis et al. (2003) meta-analysis in showing superiority for olanzapine, and that there was no evidence of industry bias of the studies they reviewed. Thus, CATIE and EUFEST are largely confirmatory of what industry and other studies had reported from the start: no difference in total psychopathology and positive symptom control between typical and atypical antipsychotic drugs other than clozapine. CATIE reported advantages for olanzapine, which we have suggested was due to the high dosage permitted for olanzapine and inclusion of a high proportion of treatment-resistant patients (Meltzer and Bobo, 2006), while CUtLASS reported trends for greater improvement in Quality of Life and symptom scores for their mixed typical/atypical antipsychotic-treated group, possibly for the reasons noted above. I suggest that it is possible to obtain further insight into the comparative efficacy of typical and atypical antipsychotic drugs by consideration of clozapine vs. typical antipsychotic drugs in non-treatment-resistant patients.
Is clozapine superior to typical antipsychotics in non-treatment-resistant patients?
The issue of whether clozapine itself is superior to the typical antipsychotic drugs, let alone whether the other atypical antipsychotic drugs are as well, for the non-treatment-resistant patients with schizophrenia, is one that has been explored and provides information relevant to the ongoing discussion about the merits of the two classes of drugs for treatment of the majority of patients with schizophrenia. In a trial with neuroleptic responsive patients, my colleagues and I found that clozapine had no advantages for psychopathology, compared to typical neuroleptic drugs, but that discontinuation from the treatment initially randomized to occurred significantly more frequently with the typical antipsychotic drugs ( Lee et al., 1994; 1999). (A more detailed report of the results of this study is in preparation because of its increased importance in light of some of the issues I address here). We reached this conclusion as the result of a study comparing clozapine and typical neuroleptic drugs in 85 patients with schizophrenia or schizoaffective disorder who were within a few years of the onset of psychotic symptoms, and who had been selected for being neuroleptic-responsive, These patients were randomly assigned to receive clozapine or typical neuroleptic drugs and evaluated over a two-year period. All ratings of psychopathology (baseline, 6 weeks, 3, 6, 12, and 24 months) were videotaped and rated by a single rater blind to treatment. The same, single but unblinded clinician treated all patients and made all decisions about drug continuation. Equivalent improvement in BPRS Total, Positive, or Negative symptoms, SANS and SAPS ratings CGI and Quality of Life measures was found. There were, however, significant differences in the number of dropouts. Of the 85 patients, nine (22.5 percent) assigned to clozapine and 19 (42.2 percent) to typical neuroleptics (χ2 = 3.73, p = .05) discontinued the typical antipsychotic drug treatment, for a variety of reasons. Significantly, two of the patients treated with typical neuroleptics developed tardive dyskinesia, and both were switched to clozapine, as were two patients who became resistant to typical neuroleptics during the course of treatment. There was no incentive for the patients, who were permitted to choose the typical agent they had had the best prior experience with, to discontinue the initially assigned typical neuroleptic, as the only other available treatment at the time was another typical antipsychotic drug.
The most important difference between clozapine and typical antipsychotic drugs in the Lee et al. study (Lee et al., 1994; 1999) was that treatment with clozapine improved some domains of cognition, particularly psychomotor speed and attention, as assessed by the Digit Symbol Substitution Test, and verbal fluency, as assessed by the Category Instance Generation and Controlled Word Association tests at six weeks, which was maintained throughout the one-year study. These improvements were not related to improvement in psychopathology or differences in EPS. We concluded that these results indicated that clozapine is superior to typical neuroleptics in improving specific types of cognitive function in some recent onset, neuroleptic-responsive schizophrenia, but not with regard to improvement in psychopathology. Carpenter et al. (1995) also called attention to the lack of advantage of clozapine over typical neuroleptic drugs in non-treatment-resistant patients, citing additional published literature to support their conclusion. The EUFEST results with atypical antipsychotic drugs other than clozapine, in first-episode patients, are in agreement with the results of Lee et al. and support the conclusion that expectation of advantage for symptom change should not be the reason for using an atypical antipsychotic drug in first-episode and non-treatment resistant-patients. But there are other reasons for preferring the atypicals as first-line treatment.
Is clozapine uniquely effective in treatment-resistant patients?
So if the typical and atypical drugs do not differ in their ability to reduce overall psychopathology in non-treatment-resistant and first-episode patients, are there any reasons to use atypicals, given their greater cost and metabolic side effects, in some cases, as first-line treatment? The International Psychopharmacology Algorithm Project (IPAP), a group of international experts including Jeff Lieberman and Wolfgang Fleishhacker, principal authors of CATIE and EUFEST, respectively, a project which I chaired, concluded that atypicals should be first-line for non-treatment-resistant schizophrenia (see www.IPAP.org). Contrast this with Rosenheck (2008), whose list of possible uses of atypicals is limited to patients with tardive dyskinesia, akathisia, or pseudo-parkinsonism. Rosenheck et al. (2008) recommends that clozapine is first-line in treatment-resistant patients. But is it truly superior to the other serotonin-antagonists in this regard?
Recently, my colleagues and I reported that olanzapine is equivalent to clozapine in improving psychopathology and cognition for treatment-resistant schizophrenia, when the doses of both are comparable: i.e., two to four times the doses needed for non-treatment-resistant patients (Meltzer et al., 2008). (It is generally not appreciated that the average dose of clozapine used for treatment-resistant patients, 300-700 mg/day, is two to three times the dose needed for non-treatment-resistant patients, i.e., 100-300 mg/day). Treatment for up to six months was required for the majority of treatment-resistant patients to respond to olanzapine, mean dose 35 mg/day, or clozapine, mean dose 550 mg/day (Meltzer et al., 2008). This small N study, though consistent with many uncontrolled studies, and the results of CATIE, where olanzapine was used at doses as high as 30 mg/day, needs to be replicated and extended. The benefits of high doses and prolonged monotherapy of clozapine or olanzapine for treatment-resistant patients may also hold for other serotonin-dopamine antagonists that are direct-acting dopamine antagonists, including quetiapine (1200-2000 mg/day), risperidone (12-20 mg/day), and ziprasidone (>160-640 mg/day) (Pierre et al., 2005; Deutschmann and Deutschmann, 2007). It does not hold for high doses of typical antipsychotic drugs (Kane et al., 1988). The recent report that standard doses of aripiprazole, a partial agonist with 5-HT2A antagonist and 5-HT1A agonist properties, is effective in treatment-resistant schizophrenia (Kane et al., 2007) needs to be confirmed, and, if valid, examined as to mechanism.
Are there reasons to use atypical antipsychotic drugs in non-treatment-resistant patients as first-line treatment?
Tardive dyskinesia
The consensus has been that about 30 percent of patients with schizophrenia are treatment-resistant. Clearly, clozapine itself, or possibly high doses of an atypical agent related to clozapine, is the treatment of choice for such patients. Should they, at lower doses, also be the first-line treatment for the other 70 percent, or, should they be second-line treatments, as some of the CATIE (Rosenheck et al., 2008; Lewis and Lieberman, 2008) and CUtLASS (Jones et al., 2006) authors sometimes seem to suggest. Clearly, reducing the risk for tardive dyskinesia is an important reason, as advocated by Gardos (1999), with partial concurrence by Lieberman (2007). I do not agree with those who minimize this risk—most patients with schizophrenia need to take antipsychotic drugs on a lifetime basis. Those who advocate the typical drugs as the ethically appropriate first-line treatment realize they must minimize the risk of TD to argue for using these drugs routinely (Rosenheck, 2008; Rosenheck and Lieberman, 2007). At least 20 percent of neuroleptic-treated patients are afflicted with tardive dyskinesia, and roughly 4-5 percent are expected to develop tardive dyskinesia with each year of neuroleptic treatment (Kane et al., 1988). Margolese et al. (2005), in a recent comprehensive review of tardive dyskinesia, which took into account dosage issues, age, and sex as risk factors, concluded that there is significantly less risk of developing tardive dyskinesia with atypical antipsychotic drugs. While the metabolic side effects of some of the atypicals—olanzapine and clozapine, in particular—must be given every consideration, there are serotonin-dopamine antagonists, e.g., amisulpride, aripiprazole, risperidone, and ziprasidone, which have mild adverse effects that are in the same range as those produced by typical neuroleptic drugs. Olanzapine and clozapine can then be reserved for those patients who do not respond to the drugs with better metabolic profiles, until and if it is shown that these other atypical antipsychotics are effective and safe at higher doses in treatment-resistant patients.
Cognitive improvement
The second major reason for continuing to favor the atypicals as a class is that cognitive improvement is more likely with the atypical antipsychotics than the typical antipsychotics. This is not the place to argue this hotly debated point, which is supported by mean changes in cognition favoring the atypicals (Woodward et al., 2005; 2007). The cognition data from CATIE (Keefe et al., 2007) did not support advantages for the atypical agents, but there are many unusual features of that study, which is still undergoing intensive reexamination (Harvey P, personal communication). Imaging studies show better brain function during cognitive tasks and positive changes in brain grey and white matter in patients receiving atypical versus typical antipsychotic drugs (e.g., Surguladze et al., 2007). Additional studies of this kind are needed. There is already extensive and rapidly growing preclinical evidence which shows that the atypical, but not the typical, antipsychotic drugs can reverse cognitive dysfunction produced by chronic NMDA receptor antagonists, e.g., PCP and MK-801, in rodents (Grayson et al., 2007), a model of cognitive dysfunction in schizophrenia that has many supporters in the basic neuroscience community. This may be related to their ability to enhance dopamine and acetylcholine release in the cortex (Ichikawa et al, 2002, Kuroki et al., 1999). What is evident to those familiar with this literature is that if these highly replicated preclinical findings have no clinical relevance, than there is an enormous waste of effort ongoing in the many academic and industry laboratories worldwide which use these surrogate measures as the basis for developing new drugs to improve or further improve cognition in schizophrenia. There is, I believe, too great a readiness to dismiss the evidence in support of the cognitive advantages of the atypical over the typical antipsychotic drugs for a significant proportion of patients, advantages which lead to beneficial changes in function in some.
In summary, the EUFEST study provides additional evidence that typical and atypical antipsychotic drugs do not differ in their ability to improve psychopathology in non-treatment-resistant patients, something we have known for some time, in my view. The EUFEST study also adds to the evidence that despite this, patients may remain on treatment with atypical agents for longer periods than with typical antipsychotics, including first-episode patients who are more prone to stop medication than more chronic patients. However, the take-home message is not that these drugs should become second-line (risperidone, clozapine), third-line (aripiprazole, quetiapine, ziprasidone), or fourth-line (olanzapine) therapy because of their supposed lack of cost effectiveness, as advocated by Rosenheck (2008) and Rosenheck et al. (2008). Rather, I believe it is the need for further research about the differences between these classes of drugs with regard to cognition and effects upon brain structure and function, in better described and circumscribed populations, using the most rigorous kind of experimental design, and more complete acknowledgement of the typical antipsychotics' greater risk to cause tardive dyskinesia.
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Hogarty GE, Schooler NR, Baker RW.(1997) Efficacy versus Effectiveness. Psychiatry Serv. 48: 1107. Abstract
Ichikawa J, Dai J, Oââ¬â¢Laughlin IA, Fowler W, Meltzer HY (2002). Atypical, but not typical, antipsychotic drugs selectively increase acetylcholine release in rat medial prefrontal cortex, nucleus accumbens and striatum. Neuropsychopharmacol 26:325-39. Abstract
Jones PB, Barnes TR, Davies L, Dunn G, Lloyd H, Hayhurst KP, Murray RM, Markwick A, Lewis SW.(2006) Randomized controlled trial of the effect on Quality of Life of second- vs. first-generation antipsychotic drugs in schizophrenia: Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1).Arch Gen Psychiatry. 63(10):1079-87. Abstract
Kahn RS, Fleischhacker WW, Boter H, Davidson M, Vergouwe Y, Keet IP, Gheorghe MD, Rybakowski JK, Galderisi S, Libiger J, Hummer M, Dollfus S, López-Ibor JJ, Hranov LG, Gaebel W, Peuskens J, Lindefors N, Riecher-Rössler A, Grobbee DE; EUFEST study group (2008). Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial. Lancet. 371(9618):1085-97. Abstract
Kane, JM (1994) Risperidone Am J Psychiatry 151 : 802-803, 1994. Abstract
Kane J, Honigfeld G, Singer J, Meltzer HY, the Clozaril Collaborative Study Group (1988): Clozapine for the treatment-resistant schizophrenic: a double-blind comparison with chlorpromazine/benztropine. Arch Gen Psychiatry 45:789-796.incidence and risk factors. J Clin Psychopharmacol. 8(Aug suppl): 52S-56S. Abstract
Kane JM, Meltzer HY, Carson WH, McQuade RD, Marcus RN, Sanchez R (2007) Aripiprazole for treatment-resistant schizophrenia - results of a multicenter, randomized, double-blind, comparison study versus perphenazine. J Clin Psychiatry 68:213-23. Abstract
Kapur, S., and P. Seeman (2000). Antipsychotic agents differ in how fast they come off the dopamine D2 receptors. Implications for atypical antipsychotic action. J Psychiatry Neurosci, 25, 161-6. Abstract
Keefe RSE, Bilder RM, Davis SM, Harvey PD, Palmer BW, Gold JM, Meltzer HY, Green MF, Capuano G, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, Davis CE, Hsiao JK, Lieberman JA, for the CATIE investigators and the neurocognitive working group (2007). Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE trial. Arch Gen Psychiatry 64:633-47. Abstract
Kuroki T, Meltzer HY, Ichikawa J.(1999) Effects of antipsychotic drugs on extracellular dopamine levels in rat medial prefrontal cortex and nucleus accumbens. J Pharmacol Exp Thera 288:774-81. Abstract
Lee MA, Jayathilake K, Meltzer HY (1999): A comparison of the effect of clozapine with typical neuroleptics on cognitive function in neuroleptic-responsive schizophrenia. Schizophr Res 37: 1-11. Abstract
Lee MA, Thompson P, Meltzer HY (1994). Effects of clozapine on cognitive function in schizophrenia. J Clin Psychiatry 55(Supplement B): 82-87. Abstract
Leucht S; (2004) Amisulpride a selective dopamine antagonist and atypical antipsychotic: results a meta-analysis of randomized controlled trials. Int. J Neuropsychopharm Suppl 1: S15-20. Abstract
Leucht S, Wahlbeck K, Hamann J, Kissling W.(2000) New generation antipsychotics versus low-potency conventional antipsychotics: a systematic review and meta-analysis. Lancet.361(9369):1581-9. Abstract
Lewis S and Lieberman, JA (2008) CATIE and CUtLASS: can we handle the truth? Br J Psychiatry. 2008 192(3):161-3. Abstract
Lieberman JA (2007) An Interview with Jeffrey A. Liebverman, Tardive Dyskinesia CNS Spectr. 12 (10) 747-750. Abstract
Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, Keefe RS, Davis SM, Davis CE, Lebowitz BD, Severe J, Hsiao JK; Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators. (2005) Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 22;353(12):1209-23. Abstract
Margolese HC. Chouinard G. Kolivakis TT. Beauclair L. Miller R. Annable L. Tardive dyskinesia in the era of typical and atypical antipsychotics. Part 2: Incidence and management strategies in patients with schizophrenia. Canadian Journal of Psychiatry. 50(11):703-14, 2005. Abstract
Marder SR , Meibach RC (1994) Risperidone in the treatment of schizophrenia Am J Psychiatry, 151: 825-835. Abstract
McEvoy JP, Lieberman JA, Stroup TS, Davis SM, Meltzer HY, Rosenheck RA, Swartz MS, Perkins DO, Keefe RS, Davis CE, Severe J, Hsiao JK; CATIE Investigators (2006). Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment. Am J Psychiatry. 163(4):600-10. Abstract
Meltzer H, Alphs L, Green A. Altamura A, Anand R, Bertoldi A, Bourgeois M, Chouinard G, Islam M, Kane J, Krishnan R, Lindenmayer J-P, Potkin S (2003): International Suicide Prevention Trial (InterSePT): reduced suicidality in schizophrenia with clozapine treatment Arch Genl Psychiatry 60:735, 2003.
Meltzer HY, Bobo WV (2006). Interpreting the efficacy findings in the CATIE study: what clinicians should know. CNS Spectr11: suppl 7: 14-24. Abstract
Meltzer HY, Bobo WV, Roy A, Jayathilake K, Chen Y, Ertugrul A, Anil Yağcioğlu AE, Small JG (2008) A randomized, double-blind comparison of clozapine and high-dose olanzapine in treatment-resistant patients with schizophrenia. J Clin Psychiatry. 69):274-85. Abstract
Meltzer HY, Burnett S, Bastani B, Ramirez LF (1990). Effect of six months of clozapine treatment on the quality of life of chronic schizophrenic patients. Hosp Community Psychiatry 41:892 97. Abstract
Meltzer HY, Li Z, Kaneda Y, Ichikawa J (2003) Serotonin receptors: Their key role in drugs to treat schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 27:1159-72. Abstract
Meltzer HY, Matsubara S, Lee J C. (1989) Classification of typical and atypical antipsychotic drugs on the basis of dopamine D 1, D 2 and serotonin2 pKi values. J Pharmacol Exp Thera 251:238 46, 1989. Abstract
Meltzer HY, Okayli G. The reduction of suicidality during clozapine treatment in neuroleptic-resistant schizophrenia: impact on risk-benefit assessment. American Journal of Psychiatry 152:183-90, 1995. Abstract
Pierre JM, Wirshing DA, Wirshing WC, Rivard JM, Marks R, Mendenhall J, Sheppard K, Saunders DG (2005).High-dose quetiapine in treatment refractory schizophrenia. Schizophr Res.;73(2-3):373-5. Abstract
Rao VA, Bailey J, Bishop M, Coppen A (1981).. A clinical and pharmacodynamic evaluation of sulpiride. Psychopharmacology (Berl). 1981;73(1):77-80. Abstract
Rosenheck RA (2008): Pharmacotherapy of first episode schizophrenia. Lancet. 371(9618): 1048-1049. Abstract
Rosenheck RA, Leslie DL, Busch S, Rofman ES, Sernyak M. (2008) Rethinking antipsychotic formulary policy.Schizophr Bull. 34(2):375-80. Abstract
Rosenheck RA, Lieberman JA (2007). Cost-effectiveness measures, methods, and policy implications from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) for schizophrenia. J Clin Psychiatry. 2007 68(2):e05. Abstract
Rummel C, Hamann J, Kissling W, Leucht S. New generation antipsychotics for first episode schizophrenia. Cochrane Database Syst Rev. 2003;(4):CD004410. Abstract
Scatton B, Claustre Y, Cudennec A, Oblin A, Perrault G, Sanger DJ, Schoemaker H. Amisulpride: from animal pharmacology to therapeutic action. Int Clin Psychopharmacol. 1997 ;12 Suppl 2:S29-36. Abstract
Surguladze SA, Chu EM, Evans A, Anilkumar AP, Patel MX, Timehin C, David AS (2007).The effect of long-acting risperidone on working memory in schizophrenia: a functional magnetic resonance imaging study. J Clin Psychopharmacol. 27(6):560-70. Abstract
Tollefson GD, Beasley CM Jr, Tran PV, Street JS, Krueger JA, Tamura RN, Graffeo KA, Thieme ME (1997). Olanzapine versus haloperidol in the treatment of schizophrenia and schizoaffective and schizophreniform disorders: results of an international collaborative trial. Am J Psychiatry;154(4):457-65. Abstract
Wells, KB: Treatment Research at the Crossroads; The Scientific Interface of Clinical Trials and Effectiveness Research (1999). Amer J Psychiatry 156:5-10. Abstract
Woodward ND, Purdon SE, Meltzer HY, Zald DH (2005): A meta-analysis of neuropsychological change to clozapine, olanzapine, quetiapine, and risperidone in schizophrenia. Int J Neuropsychopharmacol 8:457-72 2005. Abstract
Woodward ND, Purdon E Scot, Meltzer HY, Zald H (2007). A meta-analysis of cognitive change with haloperidol in clinical trials of atypical antipsychotics -dose effects and comparison to practice effects. Schiz Res 89:211-24. Abstract
www. IPAP.org; The International Psychopharmacology Algorithm Project
View all comments by Herbert Meltzer
Related News: Study Questions Advantages of Newer Antipsychotics for Early Schizophrenia
Comment by: Erik Johnsen, Hugo A. Jorgensen
Submitted 12 May 2008
Posted 14 May 2008
In our recently published systematic review of randomized effectiveness trials on SGAs (Johnsen and Jorgensen, 2008), the main findings were that chronically ill patients treated with olanzapine had longer time until treatment discontinuation and/or better drug compliance compared to those treated with the other SGAs, as well as the FGAs in those studies that had an FGA arm. The SGAs and FGAs did not differ on efficacy measures, and there were surprisingly few differences among SGAs on tolerability outcomes. The most consistent tolerability difference among the SGAs was in the area of metabolic adverse effects, where olanzapine-treated patients had more weight gain and adverse influence on cholesterol and triglyceride levels. The most pronounced difference between FGAs and SGAs on tolerability outcomes was that the FGAs were associated with significantly more extrapyramidal side effects (EPS) or discontinuation owing to EPS in the majority of studies. We noticed that this finding was also replicated in the EUFEST.
In summary, we believe the evidence thus far indicates superiority for olanzapine on the effectiveness outcome of time to discontinuation in patients with chronic schizophrenia, but olanzapine-treated patients also have more weight gain and metabolic side effects, which means that this drug does not necessarily have the most beneficial ratio of numbers needed to treat (NNT) and numbers needed to harm (NNH). The FGAs have not demonstrated superiority over SGAs in effectiveness, efficacy, or tolerability measures, and are associated with more EPS in a majority of studies, indicating a less favorable NNT/NHH ratio compared to the SGAs on this outcome measure.
As a closing remark, we believe that due to very different pharmacological properties, results from studies with a single drug FGA arm cannot be inferred to the collected FGA group. In reality only haloperidol, fluphenazine, and perphenazine have been evaluated versus SGAs in the effectiveness studies thus far, and conclusions can only be drawn for these FGAs.
Johnsen E, Jorgensen HA. Effectiveness of second generation antipsychotics: A systematic review of randomized trials. BMC Psychiatry. 2008 Apr 25;8(1):31. Abstract
View all comments by Erik Johnsen
View all comments by Hugo A. Jorgensen


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Boston Red Sox vs Texas RangersWed, June 5, 2013 - 7:10 PMFenway Park in Boston, MA
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subset: commoncrawl


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Palos Park Police Department
The Palos Park Police agency is a full service law enforcement agency with twenty-nine sworn officers who patrol the village twenty-four hours a day. We staff our field officers predicated on peak days and times when we need the most staff available. We utilize Southwest Central Dispatch, which has an Enhanced 911 system, which also serves the Palos Fire Protection District.
Some of the programs we offer include, Child Safety Fingerprinting, a Police Cadet program for teens, and an Emergency Service and Disaster Agency (E.S.D.A.) plan. A Vacation Watch program, Home Safety checks. The "You are Not Alone" program which provides for senior well-being checks and the File for Life program. Additionally we offer a Senior Safety I.D. Bracelet program and a volunteer Citizen on Patrol Service (COPS).
We work very closely with the Orland Park and Palos Heights Police Department's; we also train jointly with their officers. We are part of the Southwest Suburban Major Case Unit and the South Suburban Major Crimes Task Force.
The Palos Park Police Department is a very service oriented organization and we place quality service first and foremost.
Our mission is to provide our citizens, employees, visitors and business community quality public services through innovative public/private/intergovernmental partnerships and programs thereby offering expanded economic opportunities and safe family neighborhoods.
Palos Park Police Mission Statement
Police Department Officers
John Mahoney
Police Commissioner
Dan Polk
Police Chief
Joe Miller
Patrol Sergeants/ Officers In Charge
John Sawyer
Chris Hughes
Criminal Investigations
Investigator Barry Churin
Investigator Fran Marrocco Sr
Investigator Deb Legatzke
Emergency Services & Disaster Agency
Bill Leddin
Assistant Director
Frank Flores
Assistant Director
Matt McCurry
Matt McCurry
Frank Flores
Field Training Officers
Diana Campbell
John Winter
Ross Chibe
Patrol Officers
Kevin Pomper
Bob Taylor
Ryan McNulty
David Podkul
Jason Caiazzo
Kevin Taylor
Bob Kotsianis
Jorge Arrelo
Ross Chibe
Dave Harvin
Mike Chaffee
Diana Campbell
Mike Daly
Ross Ricobene
Jeff Cowe
Matt Novak
Fran Marrocco Sr
Mike Colavecchi
John Winter
Steve Gayton
Tom Hilton
Nick Spurgash
Mike Schabert
Jeremy Maske
Frank Slabenak
Steve Wagner
Support Staff
Police Recruit Trainees
Frank Slabenak
Support Services
Dolores Maldonado
Virg Humbel
Derek Kaczmarczyk
Joe Walters
Police Cadet Program Coordinators
Officer Nick Spurgash
Police Officer Recruit Trainee:
Kevin Pendl
Ray Sabo
Police Procedure Manual


text:
New KOTOR 1 and 2 Bundle
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Senior Member
Join Date
: Jan 2008
: Portugal
: 2,332
Current Game
: Watch Dogs
Originally Posted by
Char Ell
I haven't installed it on Windows Vista or 7, just Windows XP. From the looks of it though both are fully patched versions of the games on DVD. The readme files for both games reference installation requirements for Windows 7 but it wouldn't surprise me if you still have to use the same workarounds on Windows 7 as before.
You don't. Just received it today. I never had a problem installing and/or playing the original version on my Windows 7 laptop, but I had with my Vista desktop. So I installed it on my desktop with no problem and it plays just fine. My only (minor) complaint is the new disc menu (not in-game). Ugly and not within the design of the game, like the original one. But the game is patched and fully compatible with XP, Vista and 7.
Here's the (new) ReadMe file:
Show spoiler
(hidden content -
LucasArts, a Lucasfilm Company
Version 1.3
Thank you for playing STAR WARS® KNIGHTS OF THE OLD REPUBLIC. We recommend that you read this document to obtain updated information about installing, running, and playing the game.
Supported Operating Systems
To be able to play STAR WARS® KNIGHTS OF THE OLD REPUBLIC, you must have Windows XP SP3, Windows Vista, or Windows 7 installed and configured correctly, and your computer hardware must be compatible with DirectX 9.0b or later.
Minimum System Requirements
Required: Intel P3 1.0 GHz or AMD Athlon 1GHz
Required: 256 MB RAM
Graphics Card
Required: 32 MB w/ Hardware T&L
Sound Card
Required: 100% DirectX 9.0b compatible Audio Device
Required: DVD-ROM drive
Input Device
Required: Keyboard & Mouse
General Information
Installation Notes
Installation requires 4 GB of free hard drive space. We recommend that you have an additional 200 MB of free space available after installing the game for save games and Windows file caching.
Installing STAR WARS® KNIGHTS OF THE OLD REPUBLIC
Insert STAR WARS® KNIGHTS OF THE OLD REPUBLIC disc into your DVD-ROM drive. The launcher screen will open automatically if AutoRun is enabled on your computer. If your computer does not have AutoRun enabled, open Computer from your Windows desktop or Start Menu and double-click on the drive showing the STAR WARS® KNIGHTS OF THE OLD REPUBLIC icon, and then double-click on the program icon to begin installation. If it does not, double-click on Setup.exe in the window that opens. You will be prompted to select an installation path before your installation will begin.
Default Installation Location
* 32-bit operating systems:
* C:\Program Files\LucasArts\Star Wars Knights of the Old Republic
* 64-bit operating systems:
* C:\Program Files (x86)\LucasArts\Star Wars Knights of the Old Republic
Save Game Locations
* 32-bit operating systems:
* C:\Program Files\LucasArts\Star Wars Knights of the Old Republic\Saves
* 64-bit operating systems:
* C:\Program Files (x86)\LucasArts\Star Wars Knights of the Old Republic\Saves
Administrative Rights
You may be unable to install STAR WARS® KNIGHTS OF THE OLD REPUBLIC unless you are logged on with Administrative Rights, or are able to provide an administrator password.
After installing the game, you will be able to play the game with a Limited (Restricted) or Standard User account.
Running STAR WARS® KNIGHTS OF THE OLD REPUBLIC
* Click on the Start Menu
* Select All Programs
* Select the LUCASARTS folder
* Select the STAR WARS® KNIGHTS OF THE OLD REPUBLIC folder
* Click on STAR WARS® KNIGHTS OF THE OLD REPUBLIC icon
Options Menus
Sound & Graphic Options
You can adjust various Sound and Graphic settings through the options menu. To adjust the Music, Voice-Over, Sound Effects, or Movie volumes, you can use the left/right cursor keys or mouse. Press the ESC key or click on the Close button to exit the options screen once you have made the changes.
You can manually adjust the in-game Resolution, Brightness, Shadows, and Grass from the Graphics options menu while at the main game menu.
Advanced Graphics Settings & Performance Issues
If you encounter performance issues with STAR WARS® KNIGHTS OF THE OLD REPUBLIC you can also adjust additional options from within the Advanced Graphics Options menu. Lowering Texture settings and disabling Frame Buffer Effects, Soft Shadows, and V-Sync will help with in-game performance.
Disc Check Problems / SecuROM Analysis File
STAR WARS® KNIGHTS OF THE OLD REPUBLIC uses disc based copy protection provided by SecuROM™.
Disc Check Error Messages
* "Original Disc could not be found or authenticated"
* "Emulation Detected error"
* "Wrong disc inserted"
If you encounter any of these error messages when attempting to launch STAR WARS® KNIGHTS OF THE OLD REPUBLIC, follow the suggestions listed below for help resolving the issue:
* Reboot the computer and try launching the game again
* Make sure you have the game disc in a local optical DVD drive
* Close all other running applications, especially things such as: Clean Sweep, anti-virus software, ZoneAlarm, disc burning software (e.g. Nero, EZ CD Creator, or Roxio), and image-mounting software (e.g. Power ISO or WinISO)
* If you have more than one local optical drive, try all drives
* If you have a Virtual Drive installed, make sure it is disabled
* Make sure you have updated drivers for your optical drive AND that you have the latest motherboard drivers available
* Make sure you wait for the "Play" disc authentication after the program launches. It can take up to one-half minute or more for initial disc authentication. Your mouse pointer may change into a spinning disc pointer while the disc is authenticating.
If none of the above suggestions work, you can follow the steps outlined below to generate an analysis log file to submit to SecuROM Technical Support group for assistance. The analysis file contains important information to help analyze program launch issues that maybe encountered. After successfully creating the file, the necessary data will be exported and stored in an "AnalysisLog.sr0" file. Please perform the following steps:
Generating the Analysis File on Windows XP
* Ensure the retail game disc is in a local optical drive
* Reboot your system to ensure you start the process from a clean environment
* Locate the game launcher, which for this title is named swkotor.exe. This file will be located in the directory where you installed STAR WARS® KNIGHTS OF THE OLD REPUBLIC
* Right click (right mouse button) on the executable and several menu options will appear.
* Choose LAUNCH ANALYSYS from the menu and release the mouse button
* A disclaimer window will appear; click the YES button to proceed
* The application will generate an AnalysisLog.sr0 file within the root of your C:\ partition (hard drive)
* Another dialog will appear to signify the successful generation of the analysis file
* Click the OK button to finish
Generating the Analysis File on Windows Vista & Windows 7
If you are unable to generate an Analysis file using the steps above, or you are running Windows Vista or Windows 7, you will need to use the Command Prompt and set your system up to view hidden files and folders. This will allow you to view and access the files that you need to run the analysis from. To do this:
* Go to the START menu and click on CONTROL PANEL
* Click on APPEARANCE AND PERSONALIZATION and select FOLDER OPTIONS
* Select the VIEW tab
* Select 'Show hidden files and folders'
You should now be able to see hidden files and folders on your system. Now, to create an analysis file, complete the following steps:
* Ensure the retail game disc is in a local optical drive
* Reboot your system to ensure you start the process from a clean environment
* Locate the game launcher, which for this title is named swkotor.exe. This file will be located in the directory where you installed STAR WARS® KNIGHTS OF THE OLD REPUBLIC
* Right click (right mouse button) on the executable and several menu options will appear
* Go down to PROPERTIES
* Copy the already highlighted TARGET information, by selecting CTRL & C with the keyboard.
* From the keyboard, press the Windows key (the key between the Left Ctrl and Left Alt keys) and the letter 'R' at the same time. This will open a 'Run dialog box'
* Type in the letters 'CMD' with the keyboard and press ENTER or click on the OK button with the mouse (A DOS window should appear with a blinking cursor)
* In the DOS window, type 'CD\' from the keyboard, and press ENTER. This should take you to the root of your C:\ drive
* Now, move the mouse cursor into the DOS Window and Right-Click with your mouse, and select PASTE from the menu selection context box that appears
* Press the SPACE BAR once, and add the text '/SECUEXP' and press Enter. Your entire line should look something like "C:\Program Files\LucasArts\ Star Wars Knights of the Old Republic \swkotor.exe /SECUEXP" (your text may look different if you elected to install the game to a different directory at the time of setup)
* Press ENTER on the keyboard
* A disclaimer window may appear on your screen. - To proceed, click the YES button.
* A window stating that an Analysis log will be generated may appear, if it does, then click the OK button
Sending the Analysis File to SecuROM
* Windows XP
* An AnalysisLog.sr0 file will be saved to the root of your C:\ drive. To locate it, go to COMPUTER open your C:\ drive and you should see the 'AnalysisLog.sr0' file.
* Windows Vista & Windows 7
* The AnalysisLog.sr0 file will be stored on your desktop, or the following path:
C:\Users\<YOUR WINDOWS USER NAME>\AppData\Local\Temp\AnalysisLog.sr0
If by chance this folder is hidden, you may have to display hidden folders. Follow the steps above under "Generating the Analysis File on Windows Vista & Windows 7" to display the folders.
If you have access to do so, please zip the 'AnalysisLog.sr0' file using a program such as WinZip, WinAce, or WinRAR (to prevent email corruption).
Please email the .sr0 file or zip file and a description of your issue with as much detail as possible. Be sure to include things you have already tried. Please submit this information by attaching the analysis file and to an email and sending it to
Disclaimer: The ability to generate the analysis file has been developed with your personal interest in mind to check for possible hardware and/or software incompatibility on your PC. To shorten the analysis time, system information is collected (similar to Microsoft's msinfo32.exe program). Data will be compared with the SecuROM knowledge base to determine hardware and/or software conflicts. Submitting the analysis file is totally voluntary. The collected data is for evaluation purposes only and is not used in any other manner.
Customer Support in the UK and Ireland
Our support section of the web has the most up-to-date information available including links to patches that can be downloaded free-of-charge. We update the support pages daily so please check here first. By going to the Find Answers section and selecting the platform and game you can view the frequently asked questions. If you don't find your question there try using a keyword.
Email and Phone Support
Please consult the web for the most up-to-date contact information and opening hours for your country and language. Only technical support will be provided; hints, codes and cheats are not supported.
Note: Please do not return any game directly to Activision without first contacting Customer Support. It is our policy that game returns or refunds must be dealt with by the retailer or online site where you purchased the product.
Phone: +44 845 528 0269 (local rate)
Opening hours: Monday through Friday from 9 am – 5 pm GMT
Except for National Holidays
Phone: 01 9036 586 (local rate)
Opening hours: Monday through Friday from 9 am – 5 pm GMT
Except for National Holidays
LucasArts and the LucasArts logo are registered trademarks of Lucasfilm Ltd.*© 1991-2012 Lucasfilm Entertainment Company Ltd. & ® or ™ as indicated. All rights reserved.
Last Updated: July 19th, 2012
P.S: Here's the new menu:
Show spoiler
(hidden content -
Star Wars: In Concert | Lisbon
- Some pictures of the exhibition accompanying the event.
Last edited by Alexrd; 09-14-2012 at
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Los Angeles Lakers vs Oklahoma City ThunderSun, March 9, 2014 - 12:30 PMStaples Center in Los Angeles, CA
We are sorry, the date for this event has already passed. This event took place on 3/9/2014. Click here to view upcoming events for Los Angeles Lakers.
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text:
Bowling Green is expanding its text messaging services as a way to better inform the community of events and emergencies.
The city began using a texting service in November with golfers who subscribed for updates on special deals and golf course availability.
They say that was just the beginning of what they hoped would lead to more texting services.
"We wanted to roll out the "join golf" first and see what kind of reaction we got, and we had a really good response. We had people giving us feedback. So we thought if it worked so well for golf, we wanted to be able to reach people in other areas," said Bowling Green Public Information Officer Kim Lancaster.
Three new services are now available. You can text "join info" for info on events, road closings, and emergencies.
Text "join bgcan" for information on organizations in the community, and Spanish speaking users can text "join amigos" for updates in Spanish. You can text those messages to 2-7-0... 6-8-1... 38-28 to subscribe.


text:
Kid RockSat, August 10, 2013 - 7:30 PMDTE Energy Music Theatre in Clarkston, MI
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Kinsley Buckled Sling
Item # K74824
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Big and bold, the Kinsley Buckled Sling is the ultimate statement shoe. Infused with ADIPRENE® by adidas shock-absorbent cushioning, they are head and shoulders above other sandals for comfort and feel. It's time to make your statement.
- ADIPRENE® by adidas shock-absorbent cushioning protects the heel at impact
- ADIPRENE+® by adidas resilient forefront cushioning helps provide a responsive, dynamic push-off
- Breathable Polyurethane is moisture absorbent and odor resistant
- Polyurethane outsole offers durability for long-term wear
- Full grain leather is durable and easy to clean, extending product life
- Wedge Height: 102mm
- Platform Height: 35mm
Highly shock-absorbent cushioning protects the heel at impact
Resilient forefoot cushioning provides a responsive, dynamic push-off
Kinsley Buckled Sling is rated out of 5 by 16.
Rated 5 out of 5 by Elin from Love These! I love these sandals and have them in black and brown. They're so comfortable! There was no breaking in period. This was my best sandal find of the season.
Date published: 2013-05-30
Rated 5 out of 5 by Jemimah from Essential black sandal They'll make you taller, slimmer, more clever...and they're comfortable!
Date published: 2013-04-11
Rated 5 out of 5 by happyshoes from MY MOST COMFORTABLE HIGH HEELED SANDALS EVER! These Rockport sandals are my favourite & most comfortable high-wedge platform sandals to date! I am able to spend lengthy periods of time walking about with extremely comfy feet!!!!! They have great cushioning in the footbed, are relatively light for a chunky wedge sandal, and quite "breathable" for summer wear with leather straps and insoles. . They are an amazing shoe and the adidas ADIPRENE (shock-absorbing-heel-cushioning) technology works!!!
Date published: 2013-08-06
Rated 5 out of 5 by SummerReady13 from Walking on clouds! These shoes are extremely comfortable. They fit great an have superiror cushioning that makes you feel like you're walking on clouds. I purchased the black pair but wish my size were available in the warm oak color as well!
Date published: 2013-08-14
Rated 5 out of 5 by Sarah_Chicago from Best Shoe Ever on the Planet! I own 4 pairs of these shoes... I absolutely love them! I purchased more only because I will cry if they ever breakdown and I would risk not having them to wear! What can I say? They are so so so comfortable! I sincerely wish Rockport would make this shoe in a style that is more work appropriate. I would buy another four pairs of that style in a heartbeat.
Date published: 2015-09-18
Rated 1 out of 5 by Oregongirl from Disappointed I bought these to replace a pair I bought a few years ago from Rockport. This pair had to go back not nearly as comfy, the heel was too high to be worn at work all day. Please bring back Keira quarter strap braid style!!!!
Date published: 2014-08-07
Rated 5 out of 5 by WedgeWoman from Most comfortable wedges I've ever owned. These wedges are the most comfortable wedges I've ever owned. There is great cushioning and the leather is soft. I wear them all the time because they go with so many different outfits!
Date published: 2013-09-08
Rated 4 out of 5 by iheartshoes from comfortable sandals i thought the height may be a bit too much for me, but they are very comfortable and sturdy. i do wish they were lined though. the leather seems a little too thin.
Date published: 2013-06-05


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Betsy Hjort: On Making Windows Server, Singing with Bill and Being Technical
- Posted: Mar 31, 2008 at 12:12PM
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- 4 comments
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Oohh... Apparantly I'm yellow. Hmmm...
Right, off to see if the library has this book. Because I'm a cheapskate.
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No, this isn't the opening scene of Waterworld. One of the biggest cities in America could soon source drinkable water from sewage.
The Silicon Valley Advanced Water Purification Center, a $68 million facility that will service San Jose and the surrounding area, is set to open in October. And, though the center will source all of its water from treated sewage, it will reportedly produce water that's six times cleaner than what comes out of the tap.
"To give you an idea, this facility should be able to produce water that has a TDS (total dissolved solids) content of 40 parts per million," Marty Grimes of the Santa Clara Valley Water District said to The Huffington Post. "Now compare that to drinking water, which typically has about 250 parts per million."
But though the water might be clean, it won't be coming out of your tap anytime soon. Instead, it will be used for irrigation, landscaping, industrial processes and other uses typically reserved for recycled water. The reason? Public perception.
"It takes a long time to educate folks and grasp this concept that this water can be purified to a level that's cleaner than what we are already drinking," said Grimes to CBS.
Grimes hopes that, eventually, the public will be ready to make the switch.
"We'll have a lot of work to do before that time," he told HuffPost. "But through outreach and tours of the facility, we hope to show the public lab results proving this water is virtually free of impurities."
Such a toilet-to-tap system is already alive and well in Orange County, where water is scarcer than it is in the north. But will San Jose eventually do the same?
"In 20 years," said Grimes, "It may be our best choice."
CORRECTION: An earlier version of this story incorrectly listed the TDS levels of water in parts per billion instead of parts per million.
Also on HuffPost:
Sweet Snorkeling Pics
As humans increase atmospheric carbon dioxide concentrations, oceans absorb some of the CO2. The resulting drop in ocean pH, known as ocean acidification, has been called climate change's "equally evil twin" by National Oceanic and Atmospheric Administration chief Jane Lubchenco. Coral reefs, which are an invaluable part of marine ecosystems and tourism economies, are threatened by ocean warming and acidification. At the 2012 International Coral Reef Symposium in Cairns, Australia, 2,600 scientists signed a petition calling for international action to preserve global coral reefs, reported the BBC. Noting that 25 to 30 percent of the world's reefs are already "severely degraded," the statement asserts that "climate-related stressors [represent] an unprecedented challenge for the future of coral reefs and to the services they provide to people." A recent report from the World Resources Institute found that the Coral Triangle, an important area from central Southeast Asia to the edge of the western Pacific with many reefs, is threatened at a rate far greater than the global average.
Wine Tasting Parties
Winegrowers in France's Champagne region and scientists have already seen changes in the past 25 years, reported The New York Times last year. They have "noted major changes in their vineyards, including an increased sugar content in the grapes from which they make their wine, with a consequent decrease in acidity, and a harvest time that regularly comes two weeks earlier than it once did." Last year, the Telegraph reported that Bordeaux, one of the world's most famous wine-producing regions, may be "unsuitable for wine-growing by 2050." Yale Environment 360 explains that many European wines are tied to a specific geographical area, creating a problem for regions which may soon find themselves most suited to a new kind of grape. In the U.S., researchers at Stanford University found that climate change could mean "50% less land suitable for cultivating premium wine grapes in high-value areas of Northern California." A 2006 study published in the Proceedings of the National Academy of Sciences found that "up to 81 percent" of "premium-wine-grape production area" could decline in the U.S. by the end of this century, reported Wired. Without any adaptation measures, wine-grape production could disappear from "many areas" of the country. Wired notes, "By the law of supply and demand, that suggests the best wines of tomorrow will cost even more than the ridiculous amounts they fetch today."
Winnie The Pooh's Key Plot Point
According to the USDA, bee populations are dropping nationwide. Wetter winters and rainy summers make it harder for bees to get out and about to collect, leaving them to starve or become malnourished and more prone to other diseases. This doesn't just mean a decline in honey. We rely on bees to pollinate crops. When bees disappear, many food crops could also die off.
Spring Break, Wohoo!
As global temperatures rise this century, sea levels are also expected to increase. South Florida may be hit particularly hard. If greenhouse gas emissions are not reduced, global sea levels could rise over three feet by 2100, with a six foot rise possible. The U.S. Select Committee on Energy Independence and Global Warming notes:
This threatens to submerge Florida's coastal communities and economies since roughly 9 percent of the state is within 5 feet of the existing sea level. Rising sea level also threatens the beaches, wetlands, and mangrove forests that surround the state.
 University of Florida professor Jack Putz said in 2008, "People have a hard time accepting that this is happening here," reported the Tampa Bay Times. Seeing dead palm trees and other impacts "brings a global problem right into our own back yard," he added. Click here to see a map showing what different levels of sea level rise would look like for Florida and other states.
Cute Baby Polar Bear Videos
A November 2011 study found that polar bear litters are getting smaller as climate change causes sea ice decline. According to World Wildlife Fund, the study "found that if spring sea ice break-up occurs one month earlier than usual, 40-73 percent of pregnant females could fail to bring cubs to term." The National Snow and Ice Data Center found that in 2010, Arctic sea ice was at its lowest January level in 30 years. With decreased sea ice, polar bears may have greater trouble finding food sources. This could lead to cannibalism, which has already been observed by photographers. Environmental photojournalist Jenny Ross told BBC News in 2011, "There are increasing numbers of observations of it occurring, particularly on land where polar bears are trapped ashore, completely food-deprived for extended periods of time due to the loss of sea ice as a result of climate change."
Thanks to a failing peanut crop due to last summer's scorching hot weather, there was a shortage of peanuts in supply at the end of 2011. If temperatures continue to rise, a jump in peanut butter prices is just the prelude to what could be in store for the beloved spread.
Chocolate Cravings
A report released by the International Center For Tropical Agriculture warns chocolate could become a luxury item if farmers don't adapt to rising temperatures in Ghana and the Ivory Coast, where a majority of the world's cocoa is grown. The October 2011 report, funded by the Bill and Melinda Gates Foundation, "calls for increased research into heat and drought resistant crops, and to help transition cocoa farming to new regions that will be suitable for production in the future," reported ThinkProgress.
'Friday Night Lights' & 'Varsity Blues'
As average temperatures rise over the course of this century, states in the Southern U.S. are expected to see a greater number of days with temperatures over 90 degrees Fahrenheit each year. Hotter temperatures will mean that football players in the South will face a greater risk of hyperthermia, explains GE's TXCHNOLOGIST blog. ThinkProgress suggests, "Indeed, it is the conservative southern U.S., especially the South central and South east, who have led the way in blocking serious climate action, as it were, making yesterday's worst-case scenario into today's likely outcome."
Not Sneezing
Bad news for allergy sufferers -- climate change, and specifically warmer temperatures, may bring more pollen and ragweed, according to a 2011 study from the Mount Sinai School of Medicine in New York. Along with allergies, a changing climate may be tied to more infectious diseases. According to one study, climate change could affect wild bird migratory patterns, increasing the chances for human flu pandemics. Illnesses like Lyme disease could also become more prominent.
Keg Stands
Famed for producing some of the world's best beer, Germany could suffer from a drop in production due to climate change-induced water shortages. Barley and hops can only be grown with water, and using cheaper alternatives like corn isn't possible in Germany because of strict regulations about what you can make beer with. Research published earlier this year in the journal Nature Climate Change found that "unless farmers develop more heat-tolerant corn varieties or gradually move corn production from the United States into Canada, frequent heat waves will cause sharp price spikes," reported The New York Times. Price spikes for U.S. corn could affect prices of American macrobrews made with an adjunct ingredient like corn.
Valentine's Day Cliches
With higher temperatures expected in northern latitudes in coming decades, the U.K. has begun a program to develop strawberries that will survive in higher temperatures with less water. Since chocolate also may be threatened, could sexy chocolate-covered strawberries, a Valentine's Day staple, be endangered? According to The Telegraph, Dr. David Simpson, a scientist with England's East Malling Research, said last year, "Consumer demand for fresh strawberries in the UK has been growing year on year since the early 1990s. The British growers have done a great job of increasing their productivity to satisfy this demand between April and October. The future will be challenging due to the impacts of climate change and the withdrawal of many pesticides but the breeding programme at EMR is using the latest scientific approaches to develop a range of varieties that will meet the needs of our growers for the future."
Coffeehouse Snobs
Coffee lovers may want to get that caffeine fix before the treasured drink becomes a rare export. Starbucks raised the issue last year when the company's director of sustainability told The Guardian that climate change is threatening the supply chain for the Arabica coffee bean. Starbucks Sustainability Director Jim Hanna told the paper, "What we are really seeing as a company as we look 10, 20, 30 years down the road - if conditions continue as they are - is a potentially significant risk to our supply chain, which is the Arabica coffee bean."
Water Out West
According to a 2011 U.S. Interior Department report, "annual flows in three prominent river basins - the Colorado, Rio Grande and San Joaquin - could decline by as much [as] 8 percent to 14 percent over the next four decades," reported the Associated Press. Expected changes in temperature and precipitation are likely to alter river flows "with increased flooding possible in the winter due to early snowmelt and water shortages in the summer due to reductions in spring and summer runoffs." Mike Connor, commissioner of the U.S. Bureau of Reclamation, said, "Impacts to water are on the leading edge of global climate change." Earlier this year, the Bureau of Reclamation asked the public to suggest ideas for meeting future water demand around the Colorado River basin.
Rudolph (And Donner And Blitzen)
Reindeer, also known as "caribou" in North America, could face a difficult future in a warmer climate. According to U.S. News & World Report, "Russell Graham, associate professor of geosciences and director of the Earth and Mineral Sciences Museum at Penn State University, says global warming will most harm the animals adapted to the coldest environments, primarily those accustomed to life in the Arctic." A 2008 study found that caribou in West Greenland are "now arriving after peak foraging time, fewer calves are being born and more calves are dying," reported ScienceNews.
Yummy Pancake Breakfasts
It may be a bit harder to drown your pancakes in maple syrup in the future, studies suggest. According to a 2010 Cornell University study, "maple syrup production in the Northeast is expected to slightly decline by 2100, and the window for tapping trees will move earlier by about a month." Additionally, most maple syrup production south of Pennsylvania "will likely be lost by 2100 due to lack of freezing." Click here to watch one farmer's fight to save New Hampshire's sugar maples.
Gone Fishin'
According to a 2002 study by the Natural Resources Defense Council and Defenders of Wildlife, a warming planet does not bode well for species that thrive in cold streams. The study found that "global warming is likely to spur the disappearance of trout and salmon from as much as 18 to 38 percent of their current habitat by the year 2090." A 2011 study published in the Proceedings of the National Academies of Science produced "models [which] forecast significant declines in trout habitat across the interior western United States in the 21st century," reported The New York Times. The study claims, "The decline will have significant socioeconomic consequences as recreational trout fisheries are valued in the hundreds of millions of dollars in the United States alone."
NYC's Waterfront Real Estate
According to a 2012 report from New Jersey-based nonprofit Climate Central, thousands of New York City residents may be at risk for severe coastal flooding as a result of climate change. Climate Central explains, "the NY metro area hosts the nation's highest-density populations vulnerable to sea level rise." They argue, "the funnel shape of New York Harbor has the potential to magnify storm surges already supplemented by sea level rise, threatening widespread areas of New York City."
The Best Part Of July 4th
With droughts and wildfires hitting many parts of the U.S., municipalities from Colorado to Tennessee canceled July 4th public fireworks displays or banned personal fireworks this year, citing the fire hazards they posed. In June, a study published in the journal Ecosphere found that almost all of North America will see more wildfires by 2100, reported Reuters. The study's lead author, Max Moritz, said, "In the long run, we found what most fear - increasing fire activity across large areas of the planet."
The Non-.com Amazon
Along with deforestation, climate change also poses a serious threat to South America's Amazon rainforest. A 2009 study from the U.K. Met Office found that a global temperature rise of four degrees Celsius above pre-industrial levels would cause 85 percent of the Amazon to die off in the next 100 years. Even a two degree Celsius rise would kill 20 to 40 percent of the rainforest, reported the Guardian. In May, The Club of Rome think tank predicted a global average temperatures rise of "2 degrees Celsius by 2052 and a 2.8 degree rise by 2080," reported Reuters. Jorgen Randers, author of the club's report, said, "It is unlikely that governments will pass necessary regulation to force the markets to allocate more money into climate-friendly solutions, and (we) must not assume that markets will work for the benefit of humankind." He added, "We are emitting twice as much greenhouse gases every year as are absorbed by the world's forests and oceans. This overshoot will worsen and will peak in 2030."
Island Getaways
As global sea levels rise during the 21st century, low-lying island nations like the Maldives could see their very existence threatened. With a three to six foot sea level rise predicted by 2100, nations like the Maldives could become uninhabitable, explained The New York Times. Maldives' former president, Mohamed Nasheed, has been a tireless campaigner for the urgent need for countries to take action against climate change, arguing "You can't pick and choose on science."
Ski Bums
Although seasonal fluctuations occur and El Nino/La Nina weather patterns affect snowfall, global temperature rise may impact conditions for skiers and boarders. "The long-term trend is less snow and earlier snowmelt. This means more frustration for snow sport enthusiasts and a negative impact on the snow sports industry," writes the Natural Resources Defense Council's Theo Spencer. In May, a snow-less ski race was held in Aspen, Colorado to "highlight the effect climate change has on the outdoor recreation industry," reported the Associated Press.
Thanksgiving Dinner Food Comas
A 2010 paper in the journal Food Research International found that climate change may one day affect the cost and quality of traditional Thanksgiving dishes, reported Discovery News. Future temperature rises could impact the quality of turkey meat. Additionally, foods like "pumpkins, sweet potatoes, potatoes, grains [and] green beans ... will be sensitive to water shortages should they arise," study author Neville Gregory told Discovery News. In fact, common Thanksgiving foods were impacted by weather events in 2011, with shortages and price spikes hitting over the holidays.
The Views On Your Alaska Vacation
Earlier this year, researchers from the U.S. Forest Service confirmed that climate warming is killing southeast Alaska's mighty yellow cedars. The study, published in the journal Bioscience, found that with decreasing snow cover, the trees' shallow roots are more vulnerable to freezing, reported AP. Paul Schaberg, a U.S. Forest Service plant pathologist, said, "As time goes on and climates change even more, other species, other locations, are likely to experience similar kinds of progressions, so you might do well to understand this one so you can address those future things."
"Lady & The Tramp"-Like Scenes
Scientists at the British Met Office warn that Italy may soon be forced to import the basic ingredients to make pasta because climate change will make it impossible to grow durum wheat domestically. The crop could almost disappear from the country later this century, scientists say.
Home Sweet Home (For Kiribatians)
Along with the Maldives and other island nations, Kiribati is also threatened by climate change. Earlier this year, the president's cabinet endorsed a plan to spend about $9.6 million for 6,000 acres on Fiji's main island, reported AP. President Anote Tong told AP, "We would hope not to put everyone on one piece of land, but if it became absolutely necessary, yes, we could do it." He added, "It wouldn't be for me, personally, but would apply more to a younger generation. For them, moving won't be a matter of choice. It's basically going to be a matter of survival."
Super Duper Fast Wi-Fi Connection
A 2011 report from the U.K.'s Department for Environment, Food and Rural Affairs found that climate change could affect certain infrastructure, like wireless internet. The Guardian reports, "higher temperatures can reduce the range of wireless communications, rainstorms can impact the reliability of the signal, and drier summers and wetter winters may cause greater subsidence, damaging masts and underground cables," according to secretary of state for the environment. The Guardian notes, "The government acknowledges that the impact of climate change on telecommunications is not well understood, but the report raises a series of potential risks."
The Great Smoky Mountains' Smoke
The Great Smoky Mountains have the most annual rainfall in the southeastern U.S., which mostly falls as a light, misty rain, explains OurAmazingPlanet. A study by a team from NASA's Precipitation Measurement Missions found that "light rainfall is the dominant form of precipitation in the region, accounting for 50 to 60 percent of a year's total, governing the regional water cycle." OurAmazingPlanet notes:
The results suggest the area may be more susceptible to climate change than thought; as temperatures rise, more of the fine droplets from light rain will evaporate in the air and fail to reach the ground. Lower elevations will have to contend with not only higher temperatures, but less cloud cover.

California Beach Bums
Along the California coast, beach communities are finding that it may be impossible to stop coastal erosion as global sea levels rise. According to AP, David Revell, a senior coastal scientist at ESA PWA, acknowledged the relentless power of the sea, saying, "I like to think of it as getting out of the way gracefully." A report released in June by the Natural Resources Defense Council found that West Coast ocean levels will rise several inches in the next few decades. Sea levels along the California coast are expected to be six inches higher by 2030 and three feet higher by the end of the century. Despite the risks, another recent NRDC study found that California is one of several states with the best plans to deal with the effects of climate change.
Repeats Of The Titanic
2012 could be a record year for the extent of Arctic sea ice at its yearly summer minimum. Walt Meier, a research scientist at the U.S. National Snow and Ice Data Center, said that with recent satellite observations, "It definitely portends a low-ice year, whether it means it will go below 2007 (the record minimum in September), it is too early to tell," reported LiveScience. As sea ice declines in the Arctic, countries are anticipating a competition for control of shipping lanes and mineral extraction in the region. In Antarctica, research from the United States' Palmer Station on the Antarctic Peninsula has found that "87 percent of the peninsula's land-bound glaciers are in retreat," reported OurAmazingPlanet. Decreasing sea ice levels were also addressed in a recent spoof of Shell's plans to drill for oil in the Arctic this summer.
Crazy Sugar Highs
Climate change has already impacted sugarcane production in Indonesia. In late 2011, the chairman of the Indonesian Sugarcane Farmers Association said, "sugarcane production decreased by up to 30 percent in 2011 due to climate change that has occurred since 2009."
Warning Joe: Coffee Extinct in The Future?
Climate changes and insect invasions threaten the future supply of morning joe.
ian somerhalder
Greenpeace Australia
Adam Wiesehan
Michael Gesme
John Lingenfelder
Belle Medina
Nicastani American
Nicole Pardy
Anna Cleveland
Rick Bosman
Samiksha Sen ϟ
King Grasshopper
ISF Humboldt n.CA
Gaby Montaño
David Paterson


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Finding time for a friend
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Let $\mathfrak g$ be a simple Lie algebra over $\mathbb C$ and let $e$ be a nilpotent element in it. In the theory of finite W-algebras one often encounters the following two conditions:
1) $e$ is principal in some Levi subalgebra $\mathfrak l$ of $\mathfrak g$.
2) There exists a good even grading on $\mathfrak g$ (recall that a grading on $\mathfrak g$ is called good for e if $e \in \mathfrak g_2$ and the linear map $ad~ e : \mathfrak g_j → \mathfrak g_{j+2}$ is injective for $j \leq −1$ and surjective for $j\geq −1$).
My question is this: is there any relation between these conditions, or are they completely independent?


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Meeting Schedule
Elected faculty delegates are requested to attend each month's FDA General Assembly meeting, but all faculty (whether a delegate or not) are invited to attend these monthly sessions. Refreshments are always provided by the FDA.
The FDA Executive Committee meets once a month. Its purpose is to help plan both general FDA initiatives and the General Assembly meetings. Attendance at these meetings is restricted to the elected members of the Executive Committee, though faculty are encouraged to contact the FDA office (x14123) with any issues they would like the Executive Committee to address.
FDA Events
- FDA General Meetings (1203HE; 1:00—3:00)
Fall, 2015
September 16
October 21
November 18
December 16
Spring, 2016
February 17
March 23 (cancelled; joint meeting with PSC-CUNY on March 30th)
March 30: Joint meeting with PSC-CUNY
April 20
May 18
- FDA Social -- TBA


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Marion County Economic Development Center
Marion County Glampout
Put on your boots and join us for the first-ever GlampOut at the Marion County Kansas Park and Lake on June 10, 11 and 12, 2016.
We'll show off our Glampers . . . share some cowgirl cocktails . . . take a ride in a kayak or paddleboat . . . tell stories around the campfire . . . and make new friends! What a fun tile we will have!
Come on Girls and put your Glamp On. The fun will start Friday evening June 10th with some refreshments at a "getting to know you" gathering at 5:00 pm. Kayaks and Paddleboats will be available for any adventurous cowgirl during the event. Meet around the evening campfires and get acquainted.
Call Teresa at 620-382-8830 for more information! or email.
Vintage Campers, Tents and RV's all welcome.
Make plans to attend the GlampOut at HorseThief Reservoir, Jetmore, KS September 30 - October 2. Call 620-357-5561 for more information.
Grow with us in Marion County
When you find yourself in Marion County, Kansas, you will find communities enriched with deep historical heritage that is dedicated to preserving the past and embracing the future.
Marion County has twelve communities and each community has their own special events, shopping, museums and history. With over 25 restaurants and more than 10 Bed & Breakfasts and Motels, you can shop, drive the Santa Fe Trail across the county, explore the museums, swim at the County Park & Lake or boat at the Marion County Reservoir, play at any of our beautiful parks, then have a good meal and spend the night after viewing the stars and watching the dramatic sunset.
Marion County is also poised and ready for growth with two colleges, great schools, business parks and downtown areas where new businesses are constantly emerging and current businesses are expanding.
Come Grow with us in Marion County.
Call it what you want – agritourism, ecotourism, or nature-based tourism. Travelers from all over the United States and the world are coming to Kansas--and they are willing to pay handsomely for authentic rural experiences and the related dining, lodging, shopping and entertainment. Kansas visitors are looking for farm and ranch vacations featuring authentic experiences. They are looking for vineyards and wineries, bird watching at a country inn, hiking, biking and riding trails. They are looking for opportunities to hunt, fish, camp or just sit around a campfire and stargaze while someone tells stories of the history, culture and traditions of the area. Our tourists are seeking high quality...Read More...
Marion County Business Development Center can assist you in finding the resources you need to make your venture a success. We can help you fill in the missing piece to your business puzzle.
SBA Loans
Since its founding on July 30, 1953, the U.S. Small Business Administration has delivered about 20 million loans, loan guarantees, contracts, counseling sessions and other forms of assistance to small businesses. The SBA's current business loan portfolio of roughly 219,000 loans worth more than $45 billion makes it the largest single financial backer of U.S. businesses in the nation.
Loan program for starting or expanding your business.
Neighborhood Revitalization Program · Prior to any construction, you must contact the County Appraiser to begin the application process. · Upon issuance of your building permit, please call or visit the County Appraiser's office to see if the rehabilitation, alteration, addition, or new construction qualifies for a TAX REBATE on property taxes. · Applications for the Neighborhood Revitalization Program are available during normal business hours in the County Appraiser's office, located in the basement of the Courthouse. · There is a $50.00 NON-REFUNDABLE application fee to determine eligibility status for a tax rebate for 10 years under this program. · Please direct any further...Read More...
The Marion County Economic Development Center is your link to state and federal resources.
Loans and Grants Search Tool
Small/Home Based Bus Virtual Resource Library
How to Set Up a Home Based Business
Business Plan for Home Based Businesses
Small Business Self-Employed...
KansasWorks for Marion County
Employer Listening Tour
Kansas WorkForceOne invites you to participate in your local employer listening tour.
Ladies Fair 2016
Take a break and pamper yourself at the 2016 Ladies Fair.
Tourism Brochure
Check out the new South Central Kansas Digital Brochure
Marion County
Marion County Park and Lake
- Marion County Park and Lake website
- Marion Reservoir phone: 620-382-2421


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I have the situation that my Ubuntu session is frozen such that I cannot move my mouse or type. I managed to stop all heavy tasks by accessing a tty with Ctrl+Alt+F2, so technically it should recover to a usable state.
However, the screen is still frozen, so I suspect it would be a good idea to force compiz to restart.
It is safe to kill compiz and then restart it without any of my applications/terminals to be killed?