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CME Disclosure
Karl Goodkin, M.D., Ph.D., Professor and Director of Clinical Research, Department of Psychiatry and Behavioral Neurosciences, Cedars-Sinai Medical Center and Professor in Residence, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, UCLA.
Advisor: Advanced Immunit; Speaker List: Merck; Grant Applicant: Janssen, Amgen
Supported in part by NIMH grants MH58532 and MH75658.
Address correspondence to Karl Goodkin, M.D., Ph.D., Department of Psychiatry and Behavioral Sciences, Cedars-Sinai Health System, 8730 Alden Dr., E-105, Los Angeles, CA 90048; e-mail: firstname.lastname@example.com.
The HIV/AIDS epidemic is not considered "under control" in the United States. An unacceptably high incident case rate has been sustained over the past decade. CDC now advocates for routine HIV antibody testing to be offered in all health care settings. The psychiatrist can play an important role in identifying HIV high risk behaviors, in presenting the option for HIV antibody testing, and in providing follow-up with counseling. The high risk for HIV infection among the severely mentally ill also directly involves the psychiatrist today in HIV/AIDS care. Anxiety, depressive spectrum, neurocognitive, and psychotic disorders present with symptom profiles and in settings that are specific to HIV infection and require the need for individually tailored psychiatric care. Guidelines for the psychiatrist treating HIV infected patients are available. It is incumbent upon the practicing psychiatrist to maintain familiarity with these guidelines and offer the capacity to treat the psychiatric disorders that occur in this patient population.
The number of persons with HIV-1 infection in the United States has continued to rise, consistently increasing at an estimated 56,000 per year for the past decade. Thus, the HIV/AIDS epidemic cannot be considered "under control" at this time. Since the introduction of highly active antiretroviral therapy (HAART) combination regimens in late 1995, great gains have been made in decreasing the morbidity and mortality of the disease. Nevertheless, replication of HIV-1 is known to continue at a very low level despite "nondetectable" levels of HIV-1 RNA in the peripheral blood (1). It has also been shown that HIV-1 replicates at a relatively higher level in the CSF than in the plasma in patients with a diagnosis of HIV-associated dementia (HAD) as opposed to those with no neurological disease (2). These results are supported by other studies showing that independent HIV-1 replication in the CNS predominates in advanced disease and is contributed to by CNS-derived virus. Hence, the CNS has been designated as a "reservoir" maintained by HIV-1 in the face of currently effective systemic treatment. As a result, increasing concern has been directed to the neuropsychiatric outcomes of HIV-1 infection: HIV-1-associated asymptomatic neurocognitive impairment, mild neurocognitive disorder (MND) [formerly minor cognitive-motor disorder (MCMD) (3)], and HAD [formerly AIDS dementia complex (ADC)] (4). After a brief background on HIV/AIDS, this article will focus on the information psychiatrists need to know today for 1) the evaluation of risk for HIV-1 infection, 2) HIV-1 antibody testing and related counseling, 3) the secondary prevention of HIV-1 disease progression, and 4) the diagnosis and treatment of neuropsychiatric disorders in HIV-1 infected persons. (Hereafter, I will refer to "HIV-1" as "HIV" for general usage, as the prevalence of HIV-2 is very low in the United States.)
The Centers for Disease Control and Prevention (CDC) began tracking cases of AIDS in 1981. Human T cell lymphotropic virus type III (HTLV-III, later to be called "HIV") was isolated in 1983 (5). The dementia associated with HIV infection was first characterized as caused by HIV itself in 1986 (6, 7). In the revised CDC case definition of AIDS of 1987, "HIV encephalopathy" was included as an AIDS-defining event (8). The CDC staging system and the AIDS case definition were both revised in 1993 (9). The CDC staging system was revised to be defined by three clinical stages (A = asymptomatic, B = early symptomatic, and C = late symptomatic/AIDS). In addition, immunological disease staging was added to this staging system and defined by the number of CD4+ T "helper" lymphocytes, which are directly invaded and killed by HIV: 1) CD4 cell count ≥500 cells/mm3, 2) CD4 cell count of 200—499 cells/mm3), and 3) CD4 cell count of <200 cells/mm3. In the 1993 revision of the CDC AIDS case definition, the major change was that any patient with a CD4 cell count <200 cells/mm3 would be defined as having AIDS, regardless of whether any symptoms referable to HIV infection had been experienced. In addition, the AIDS case definition was expanded to include invasive cervical cancer (as part of recognizing gender-specific complications), pulmonary tuberculosis, and recurrent bacterial pneumonia as AIDS-defining conditions.
Regarding treatment, before 1987, there was no medical treatment specifically for HIV infection itself. That year, azidothymidine (AZT) [now referred to as "zidovudine" (ZDV)] was approved by the Food and Drug Administration (FDA). ZDV acts by the inhibition of the reverse transcriptase enzyme of HIV. In late 1995, the FDA approved saquinavir, the first of the class of drugs known as the protease inhibitors. The additional clinical impact of the introduction of this class of antiretroviral medications was recognized by the use of the term "HAART." Next was the development of a class of drugs acting at a different site of the reverse transcriptase enzyme (the non-nucleoside reverse transcriptase inhibitors). This class includes efavirenz, a drug with a greater than 50% rate of CNS side effects, although these side effects seem to be mild-to-moderate, relatively short-lived (up to 200 days) to resolve spontaneously, and to not generally require switching of the antiretroviral regimen (10, 11). Subsequently, the fusion/entry inhibitors (with enfuvirtide and then maraviroc) and an integrase inhibitor (raltegravir) were introduced.
The current high-risk behaviors of major concern for contracting HIV infection are unprotected sexual intercourse and injection substance use. Unprotected sexual intercourse by the rectal route is particularly high-risk, because the friability of the rectal mucosa is greater than that of the vaginal mucosa. As a result, HIV is more likely to be introduced into the blood. Hence, men who have sex with men (MSMs) may be at particularly high risk; heterosexuals regularly practicing unprotected rectal intercourse are also at higher risk than the general population. It should be noted that high-risk sexual behavior characterizes the risk level of an individual patient, not membership in a "high-risk category."
Injecting psychoactive substances with shared needles or unsterilized paraphernalia places a patient at high risk also because of the direct introduction of HIV into the peripheral blood, although, interestingly, black tar heroin has recently been demonstrated to be associated with a lower risk than white powder heroin (12). As discussed above for MSMs and heterosexuals who engage in high-risk sexual behavior, injecting drug users are also at high risk when they continue to inject psychoactive substances directly into their blood and when they use unsterilized equipment, rather than by their membership in the category of "injecting drug users." Of note, behavioral modifications to reduce the high-risk behavior for unprotected sexual intercourse and for injecting psychoactive substance users have been proven to be efficacious. The psychiatrist interviewing a new patient should routinely screen for HIV risk factors when taking a sexual and substance use history. It should be noted that this need is not reduced by the assumption of a lack of multiple sexual partners, by marriage, or by the patient's own presumption that he or she is not at risk for HIV infection. In addition, HIV screening should be conducted through the life span of sexual activity to include patients older than 50 years of age. Recently, the incidence of HIV infection in this group has been noted to be significantly increasing. In addition, the prevalence of HIV infection at an older age has risen because of the long-term salutary effects of HAART. Alcohol and non-injection substance use also exposes a patient to high risk for HIV infection owing to decreased decision-making capacity as a result of increased frontal lobe disinhibition at the time of sexual activity. The HIV-seronegative patient exposes himself or herself to HIV and other infections and their associated illnesses, whereas the HIV-seropositive patient exposes himself or herself to reinoculation with HIV itself and an increased HIV load as well as to other infections. It should be recalled that follow-up counseling with HIV-seropositive and HIV-seronegative individuals about high-risk activity is, therefore, part of comprehensive clinical care for the patient as well as a public health mandate.
In the HAART era, young, minority MSMs in particular are at high risk. In addition, those who have recently been incarcerated have been targeted as a high-risk group of special concern. Women of color who are disempowered due to histories of physical and/or sexual abuse and low socioeconomic status are, likewise, at high risk. Further, and perhaps most concerning, is the fact that there is a growing complacency regarding becoming HIV-infected in the general population due to an overestimation of the effects of HAART. To be successful, intervention strategies must target behavioral change, not solely attitude change and knowledge acquisition. The ongoing stigma of HIV infection, AIDS phobia, and homophobia all operate against HIV risk recognition and testing. Although older persons have now been recognized to be at increased risk for HIV infection related to increased sexual activity with use of the cGMP-dependent phosphodiesterase inhibitors (e.g., sildenafil, vardenafil, and tadalafil), there is a lack of specific prevention messages for this population. Finally, people with severe mental illness are also at increased risk for HIV infection (from 4.0% to 22.9%) (13), bringing the message directly into the purview of the practicing psychiatrist today.
To ensure a provider-patient relationship conducive to optimal clinical and preventive care, the CDC now recommends that diagnostic HIV testing should be a part of routine clinical care in all health care settings, similar to screening for other treatable medical conditions, and also that the patient's option to decline HIV testing be preserved (14). In populations with a prevalence of undiagnosed HIV infection of ≥0.1%, HIV screening is as cost-effective as the screening programs for other chronic diseases. HIV antibody testing is specifically indicated for a patient confirmed to be at high risk who is willing to undergo the procedure after it has been completely explained. The rationale should be presented as a direct referent to the HIV risk factor under which the patient qualifies as "high." Once high risk is established, the test itself should be fully explained to the patient, and consent should be sought (note that there are rare exceptions to the need for informed consent, defined by state law). Currently, there are a wide variety of tests available, including tests of blood (used with the first FDA-approved HIV antibody test in 1985) as well as of urine and saliva. The rapid test now provides results within 24 hours. It should be pointed out that HIV antibody tests in the United States now identify not only HIV type 1, which is endemic in the Unites States, but also HIV type 2, which is not. Since 1992, all U.S. blood donations have been tested with a combination HIV-1/HIV-2 test sensitive to antibodies to both viruses.
For testing done in a clinical setting, the next step in HIV antibody test counseling is transmission of the test results. Provision of formal feedback to an HIV-seropositive person to prevent new HIV infections (i.e., secondary prevention) is of clear-cut efficacy. However, this benefit is less clear for such feedback when provided to an HIV-seronegative person (i.e., primary prevention) immediately after the seronegative test results.
From the psychiatric point of view, it is expected that the distress due to an HIV-seropositive result would resolve over approximately 6 weeks. If not, a mental health referral should be considered; otherwise, a psychiatric disorder may ensue. The most common form of disorder is an adjustment reaction with various types of mood disturbance (particularly anxious mood), reactions with disturbances of conduct, and reactions with mixed disturbances. Only a minority of 20% will have chronic anxiety in the asymptomatic stage (when the aim is to define serostatus) (15). This subgroup changes over time in longitudinal studies, suggesting that a smaller percentage may develop an anxiety disorder. Other disorders seen in this situation include major depressive disorder and recidivism of alcohol and substance use disorders. Treatment is guided by DSM-IV-TR diagnosis and by APA HIV/AIDS treatment guidelines (16, 17); most commonly, patients with adjustment disorder will respond to supportive therapy without psychopharmacotherapy.
Secondary prevention of the progression of HIV infection refers to the prevention of HIV-associated immunosuppression as well as clinical disease progression, e.g., to AIDS-defining conditions such as HAD, cryptococcal meningitis, CNS toxoplasmosis, primary CNS lymphoma, invasive cervical cancer, Kaposi's sarcoma, Pneumocystis carinii pneumonia, tuberculosis, and Mycobacterium avium complex infection, among others. A major approach to the prevention of HIV disease progression is the optimization of adherence to antiretroviral regimens, which require 95% adherence to achieve and maintain nondetectable levels of HIV load in plasma (i.e., <50 HIV-1 RNA copies/ml). In addition, a number of life style factors are relevant to the secondary prevention of disease progression. These include maintaining a normal total lean body weight, optimizing nutritional status, limiting alcohol and substance use (including caffeine intake), discontinuation of cigarette smoking, maximizing sleep quality, and maintaining a regular exercise (preferable aerobic) regimen (18). For example, related to weight control, dronabinol, which is closely related to tetrahydrocannabinol (THC), may be used to maintain body weight but should be used with caution, as THC is associated with decrements in several immune functions and may also cause mental confusion. As another example, the prevalence of cigarette smoking is estimated to be 50%—70% among HIV-seropositive persons, compared with 20.8% overall in the general population. In the HAART era, smoking cessation has become a more important target than ever before, given its better recognized association with decrements in immune measures (CD4 cell count and mucosal immunoglobulin levels); an increased incidence of AIDS-defining conditions; the associated occurrence of pneumonia, myocardial infarction, and malignancy; and the increased mortality risk, compared with that in HIV-seropositive non-smokers. Of note, varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, may have advantages over bupropion SR for smoking cessation in HIV infection.
As noted above, adjustment disorder is frequently seen after serostatus notification and is the most common psychiatric disorder manifesting with anxiety. Nevertheless, the HIV-seropositive patient referred for anxiety warrants careful diagnostic evaluation. General medical causes of anxiety have been noted, such as early symptoms of pneumonia presenting with anxiety and agitation related to hypoxemia. For those patients with anxiety of longer than 6 months duration and unrealistic worries, generalized anxiety disorder is diagnosed and has been noted in 15.8% of HIV-seropositive persons versus 2.1% of the general population (19). Panic disorder, known to be associated with viral infections, cocaine use disorder, and major depressive disorder, has been noted in 10.5% of HIV-seropositive persons versus 2.5% of the general population and has been associated with an elevated pain level in HIV-infected persons (20). Posttraumatic stress disorder has likewise been reported at an elevated rate among HIV-infected persons (21), which may, at least in part, be related to a history or trauma as well as physical and sexual abuse. Such a history could, in turn, lead to a decreased sense of empowerment and a decreased likelihood of negotiating HIV precautions in high-risk situations. Psychopharmacotherapy for these conditions should be avoided, if at all possible. Nevertheless, at least initially, it may be useful to use psychopharmacotherapy to support the patient's sense of control and autonomy. The most common anxiolytic therapies used, the benzodiazepines, are sedating, interact with alcohol, foster dependence, and are associated with drug interactions on the cytochrome P450 (CYP) 3A4 isoenzyme system particularly, which is strongly inhibited by the protease inhibitors. As noted, the anxiety disorders may respond to supportive therapy, cognitive behavior therapy, progressive muscular relaxation training, self-hypnosis, cognitive imagery, and biofeedback without anxiolytic therapy. When pharmacologic treatment is deemed necessary, selective serotonin reuptake inhibitors (SSRIs) (along with venlafaxine, which has a low potential for drug interactions), are generally preferred to the benzodiazepines. However, short- to intermediate-acting benzodiazepines with no active metabolites, such as lorazepam and oxazepam, are also frequently chosen. Buspirone, which is nonsedating, safe in overdose, and has no abuse potential is an option to consider, but its delay of onset is significant. Randomized controlled trial evidence in the general population has been reported to support the use of pregabalin, specifically for generalized anxiety disorder (22). Pregabalin has the advantages of not being protein bound and not being associated with drug interactions on the CYP isoenzyme system.
Disorders associated with depressed mood have been estimated to occur in a majority of HIV-infected patients over the course of their infection. When an HIV-infected patient is confronted by the first symptoms referable to HIV, which are frequently not AIDS-defining symptoms, the patient's shell of optimism that she or he will never have a symptom is cracked. The resulting future uncertainty spawns an increased frequency of depressive spectrum disorders, including adjustment disorder, major depressive disorder, and dysthymic disorder. Recently, a prospective study confirmed a relationship between the history of symptomatic HIV infection and subsequent major depressive disorder in HIV-infected patients (23). Physical and psychological symptoms are also associated with an elevated level of suicidal ideation, which remains a concern in the HAART era (24). Further, elevated physical symptom burden is associated with psychoactive substance use and an elevated pain level (25). Thus, the patient must learn a way to adjust to the increased level of uncertainty that is associated with an elevated physical symptom burden. Of note, persons with the triple diagnosis of a psychiatric disorder, a substance use disorder, and HIV/AIDS are particularly disposed to major depressive disorder, with 72.9% of this group qualifying for this diagnosis in one recent study (26). In the differential diagnosis of depressive disorders in HIV infection, one must include disorders due to HIV infection itself (including HIV wasting syndrome and early HAD) as well as toxicities of medications prescribed to control HIV infection or its associated conditions (e.g., interferon-α for concomitant hepatitis C virus infection). Concomitant medications may also show salutary effects for depressive spectrum disorders, such as testosterone treatment in the setting of testosterone deficiency (which also treats fatigue). Likewise, ketoconazole, an antiglucocorticoid drug used for control of candidiasis, has been associated with decreases in major depressive disorder (27), as has dehydroepiandrosterone, another glucocorticoid antagonist, specifically in subsyndromal major depressive disorder in HIV-infected persons (28). Early HAD, presenting with apathy, lethargy, and social withdrawal, may be confused with major depressive disorder. However, the cognitive symptoms of helplessness, hopelessness, and low self-worth are generally absent, as are the primary affective symptoms. Regarding the impact on HIV disease itself, major depressive disorder may be treated with the same medications that would be indicated outside of HIV infection. However, important considerations are side effect profiles, the potential for drug interactions, and the neuroinflammatory impact of major depressive disorder itself. Regarding side effect profiles, in the patient manifesting with psychomotor retardation, activating antidepressants without effects on the CYP isoenzyme system in the liver, such as venlafaxine, may be preferred. Of the SSRIs, paroxetine has been favored as well as citalopram. Fluoxetine should be avoided because of its long half-life and its metabolism by both CYP 2D6 and 3A4 isoenzymes, which are also used by the protease inhibitors and the non-nucleoside reverse transcriptase inhibitors, potentially leading to drug interactions. Bupropion should be avoided because of its seizure diathesis combined with the potential that HIV-infected patients may manifest this diathesis at a low dose, given that HAD, for example, is associated with an increased frequency of seizures. The psychostimulants may be useful as a second-line option for the treatment of depressive disorders, particularly if there is concomitant neurocognitive impairment. In addition, testosterone deficiency should be assessed and treated in the setting of depressive disorders among HIV-infected persons. Finally, the relief of major depressive disorder itself may be expected to be associated with a reduction in proinflammatory cytokines in the brain (e.g., tumor necrosis factor-α, interleukin-1, and interleukin-6) (29). This neuroinflammatory impact of major depressive disorder could contribute to HIV-associated neurocognitive disorder pathogenesis, which may be alleviated by the successful treatment of major depressive disorder.
Unlike anxiety disorders (frequently seen in the asymptomatic stage and just after diagnosis of HIV seroconversion) and depressive spectrum disorders (frequently seen with the appearance of the first symptoms related to HIV infection and in early symptomatic HIV disease), the neurocognitive disorders are most commonly seen in the late symptomatic stage of HIV disease, i.e., "full-blown" AIDS. The recently promulgated Frascati Conference revision of the American Academy of Neurology (3) criteria recognizes two clinical neurocognitive disorders: MND and HAD (4). For a diagnosis of MND, there must be mild neurocognitive impairment in at least two domains of cognitive performance and, at most, a minor functional impairment in daily living, insufficient severity for a diagnosis of HAD, and no other known etiology for the symptoms. For a diagnosis of HAD, there must be severe cognitive impairment in two or more domains, at least a moderate level of functional status impairment due to the cognitive symptoms, a lack of clouding of consciousness (i.e., delirium), and no support for another etiology accounting for these symptoms. It should be noted that it is preferred that deficits in neurocognitive domains are established by formal neuropsychological testing. However, under many circumstances in clinical practice, it may not be feasible to obtain formal neuropsychological testing; thus, broad, screening tests, although less definitive, may be used to establish neurocognitive deficits in such patients, as noted in the Frascati Conference criteria. HAD is an AIDS-defining diagnosis and may be the first symptom of AIDS in 10%—25% of patients. Both MND and HAD have been reported to have declined in incidence by as much as 50% since the introduction of HAART. This decline results in an estimate of 7%—10% of patients with AIDS who will have HAD and 12%—15% of early symptomatic patients as well as 25% of late symptomatic patients who will have MND. The Frascati Conference also coined the condition "asymptomatic neurocognitive impairment" (ANI) (or subclinical neurocognitive impairment) (4). This condition occurs when there is significant cognitive decline in two or more domains of neuropsychological performance but no significant decline in functional status. It is important to note that ANI is a "condition," not a "disorder." It is estimated that ANI, as opposed to MND and HAD, has not significantly declined in prevalence in the HAART era. In fact, ANI may constitute the substrate for an eventual recrudescence of HAND in the future, should resistance to antiretroviral medications become widespread.
The Mini-Mental State Examination is used widely as a screening test for dementia. It has been used in the specific context of HIV-associated neurocognitive impairment and is cited as an alternative to formal neuropsychological testing by the Frascati Conference criteria (4). Nevertheless, it is suboptimal as a broad screening test for HAD, in contrast to the HIV Dementia Scale (HDS) (30). The HDS was specifically developed to screen for subcortical dementia caused by HIV. In addition, the International HIV Dementia Scale (IHDS) (31) may be justified and used when necessary as a more culture-fair screening device than the HDS. When such broad neurocognitive screening tests are themselves not feasible to administer, score, and interpret, it is worth noting that large groups of patients may be simultaneously screened with a self-report measure known as the Medical Outcomes Study-HIV cognitive functioning subscale. This four-item subscale has been shown to have a significant relationship to performance on formal neuropsychological tests (32).
The diagnosis of a neurocognitive disorder due to HIV presumes that results of a workup for other disorders are negative. Such a workup should include computed tomography or magnetic resonance imaging of the head to rule out CNS toxoplasmosis and primary CNS lymphoma, among other illnesses. A lumbar puncture should be done to rule out cryptococcal meningitis as well as neurosyphilis and polymerase chain reaction testing should be used to rule out other diseases (such as cytomegalovirus encephalopathy and progressive multifocal leukoencephalopathy caused by JC virus). The workup should also include screening for metabolic causes (such as hepatic and renal encephalopathy) and for psychoneurotoxicity of prescribed medications (such as the antiretroviral efavirenz and interferon-α for hepatitis C virus coinfection) as well as psychoactive substance use (e.g., cocaine and methamphetamine). Symptoms of systemic HIV disease progression that might be associated with neurocognitive impairment, such as fatigue and wasting, should also be ruled out. Finally, primary psychiatric disorders manifesting with symptoms related to neurocognitive dysfunction, such as major depressive disorder, must also be considered in the differential diagnosis. Only after this extensive workup has been conducted and results documented to be negative can a diagnosis of HAND be justified. Regarding treatment, HAD has been better studied than either MND or ANI. The CSF-penetrating antiretroviral medications have received the greatest attention; yet to date results to support specific agents are limited to the use of zidovudine and, to a lesser extent, abacavir, nevirapine, and indinavir. The recently approved agents acting by novel mechanisms, maraviroc and raltegravir, are of current interest. Anti-inflammatory agents active in the CNS (e.g., N-acetylcysteine) have been investigated to a limited extent without clear-cut benefits. Neurotransmitter manipulation is also of treatment relevance. Although results with N-methyl-d-aspartate receptor antagonists (e.g., memantine), decreasing glutamatergic activity, have been disappointing to date, agents increasing dopaminergic transmission, including the psychostimulants (33) (which also treat concomitant fatigue) and dopaminergic agonists (34) have garnered some support over time. The combination of a short-acting form of methylphenidate with a long-acting form may be particularly useful. The short-acting form may be used to establish the effective total daily dose, followed by a switch to the long-acting agent on a milligram-per-milligram basis, which, in turn, is followed by supplementation with the short-acting agent as needed. However, it must be cautioned that empirical data supporting this specific dosing strategy are lacking, and this treatment is palliative rather than pathophysiologically based.
Psychosis associated with HIV infection has been less frequently studied than the foregoing psychiatric disorders. There are many causes for psychotic symptoms in an HIV-seropositive patient. These include delirium, late-stage HIV-associated dementia, mania (which may be due to HIV infection itself), recurrence of premorbid psychotic illnesses (particularly in the severely mentally ill), psychoactive substance intoxication, antiretroviral medication toxicities (e.g., efavirenz, particularly in patients with the CYP2B6-G516T polymorphism) (35), and general medical conditions manifesting with psychotic symptoms (e.g., cryptococcal meningitis and neurosyphilis). Although less is known in this area, it is recognized that antipsychotic medications are effective in treating psychotic symptoms in this setting. With the established long-term efficacy of HAART and the general association of psychotic symptoms with late-stage HIV disease manifestations (such as delirium and dementia), the overall prevalence of psychotic disorders among HIV-seropositive patients is expected to increase. Of note, with regard to the treatment of psychosis in this setting, there are special concerns associated with the choice of antipsychotic medications in HIV-infected persons (36, 37). Specifically, the high-potency typical drugs are associated with high rates of extrapyramidal reactions, to which HIV-infected patients are highly sensitive. Similarly, the low-potency typical drugs are associated with anticholinergic side effects, another area of high sensitivity in HIV-infected patients. Thus, the atypical drugs are generally considered to be preferred; however, these drugs present a distinct toxicity problem, that of metabolic syndrome, to the HIV-infected patient. The toxicity of metabolic syndrome is of special concern to an HIV-infected patient because this syndrome is also a toxicity of the antiretroviral medications themselves and has been associated with an increased risk for the occurrence of myocardial infarction and cerebrovascular accident (as well as HIV-associated neurocognitive impairment). Thus, the atypical antipsychotic agents less likely to be associated with the metabolic syndrome, ziprasidone and aripiprazole, might be considered the first-line choices, although data do not yet exist to support these specific choices and low-dose treatment with the typical antipsychotics, e.g., haloperidol, is also effective and may be well tolerated.
Complacency regarding the spread of the HIV pandemic is not justifiable, either worldwide or in the United States. Psychiatric disorders are relevant throughout the stages of HIV disease progression. Psychiatrists need to be aware of HIV risk factors and screen regularly for them in their patients. HIV antibody testing is now being promoted by the CDC as routine testing in clinical medical settings, including psychiatric settings. Psychiatrists can play an important role in reducing HIV transmission and in secondary prevention of HIV disease progression as well.
Anxiety disorders may occur in several forms, tend to occur soon after seroconversion, and may frequently be treated effectively without the use of pharmacotherapy. Depressive disorders tend to occur after the first symptoms of HIV infection or in association with a high overall symptom burden. These disorders may be effectively and safely treated with standard antidepressant therapy. Neurocognitive disorders show a predilection for late-stage HIV disease, require a thorough medical workup, and may be treated with a variety of agents (or combinations) including the psychostimulants, CSF-penetrating antiretroviral medications, and CNS anti-inflammatory medications. Psychosis in HIV infection has been studied least among the psychiatric disorders; it may exist premorbidly and occur as a result of HIV infection of the brain or its complications. The choice of antipsychotic medication, which must be tailored to the needs of the specific patient, generally is difficult in HIV-infected patients.
I acknowledge the support of Dr. Enrique López and Dr. Guadalupe Morales in the preparation of the final document.
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A Marmol Radziner–designed prefab house, trucked onto a remote Northern California site, takes the pain out of the construction process.written by: Jaime Gillinphotos by: Dwight Eschliman11.23.11
Four Walls and a Screw-Top
What does a $9.99 bottle of screw-top wine have to do with a prefab house? Vetter Denk made the connections in an innovative getaway for an enterprising vintner.written by: William Lambphotos by: J.J. Sulin08.21.09
Upwardly Mobile Homes
When it comes to real estate, the trailer park gets a bad rap. But some designers think that this forsaken corner of the market is worthy of reevaluation—and even resuscitation.written by: Rick Polito05.13.09
Looking Inward
For Paul and Shoko Shozi, a pair of retiring Angelenos, the goal was to shut out the neighborhood but bring in the sunny skies. Their new prefab home, the Tatami House, designed by Swiss architect...written by: Aaron Brittphotos by: Jessica Haye and Clark Hsiao11.17.11
On Your Mark, Get Sett
Austin-based modern prefab designer Kimber Reed wants you to space out.written by: Mitchell Alan Parker08.15.12
Frank Vafaee of Proto Homes
In 2008, Frank Vafaee, Manish Desai, and Andre Farhang founded Proto Homes. The Los Angeles-based company designs, builds, and sells homes as products. "When you buy a phone or a car, you...written by: Miyoko Ohtake05.20.11
Barely There
If not for the dawn appearance of the bear, which came loping toward Maem Slater-Enns and her then six-month-old daughter as they sat contemplating the water, the Enns family might still be...written by: Deborah Bishopphotos by: Thomas Fricke02.01.09
iT House, Joshua Tree
The iT House brings together raw industrial aesthetics with the tactics of green design to forge a new home in the sunbaked wilds of California's east.written by: Frances Andertonphotos by: Gregg Segal02.28.09
Green & Affordable Prefab Home Debuts in Palm Springs
Tours of John Lautner's Elrod House or the Annenberg's newly re-opened Sunnylands may leave us wondering if we could ever afford a modernist luxury for ourselves, but thankfully...written by: Carren Jaophotos by: Izumi Tanaka02.17.12

subset: commoncrawl


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WeatherBug Google Desktop Gadget
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Tuesday, February 22, 2011
February Bee Blocks
I based my second Do. Good Stitches block on this one from Flickr.
{Sew} Beautiful: Emily asked for drunk love blocks on the other end of the spectrum, with no intentional wonkiness. So, mission accomplished: All wonkiness seen above was most certainly not intentional. : )
And finally, this isn't really a bee block, but Jenny of Cut. Sew. Iron. Repeat recently put out a call for cross blocks to be included in a quilt for an AIDS fundraiser. Since I had my red fabric out for my Do. Good Stitches block, I whipped up one for that project as well.
13 comments:
oh! thank you so much for helping out! your block looks fabulous! all of them actually!!ReplyDelete
I loved the "no intentional wonkiness" instruction too. :) Even on my best days, there's still a little wonkiness!ReplyDelete
LOL...you guys....what a cheerful bunch..you know that is what makes this so much fun.....nice to know you....each and every one....ReplyDelete
I think maybe you broke through your wonking block - those wonky stars blocks look fantastic! Your block for Emily turned out really awesome as well, I can tell any random wonkiness was fully unintentional - I loved that part of Emily's instructions, too. :)ReplyDelete
Nice wonk! And I agree on the red background with the pink stars - very cool!!ReplyDelete
these are gorgeous...i really love the multiple stars in the one pink blockReplyDelete
Awesome blocks! I love that you guys appreciated that. No worries either way! :) I'm so excited to see those drunk love blocks popping up! :)ReplyDelete
Your wonky star is perfect. The red does look fantastic.ReplyDelete
Hi Lee! Great 'wonk' happenin' there! ; )ReplyDelete
Great blocks! I really like your stars!ReplyDelete
Love your blocks, they turned out fab! I'm afraid I'm pretty wonky at the best of times!ReplyDelete
they're gorgeous... those pink stars really *shine*. :)ReplyDelete
Your blocks look great! I am hoping to get to Emily's block tonight, somehow that one slipped by me this month! :)ReplyDelete


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The TS26 Car Seat Adaptors attaches a Maxi Cosi, Cybex, phil&teds Alpha and Mountain Buggy Protect infant car seats to phil&teds hammerhead, black classic, explorer, dot, navigator and navigator with auto stop strollers.
Consistent with our commitment to safety we are making available to all TS26 customers a free replacement TS26.
Our continuous improvement process suggests that the TS26 is brittle at very low temperatures, and could break or crack. We wish to avoid any such incident.
Consumers should CEASE using their TS26 car seat adaptors and register online for a free replacement.
Note: problems with this form on mobile devices?
We suggest using a desktop/laptop or trying an alternative web browser.
Only the TS26 travel system is affected and is identifiable by an identification label on the right side adaptor. New and replacement TS26 have an updated label (TS26 2.0) PLUS an additional max load label on both left and right adaptor.
Any queries please contact our trained customer services representatives by email:
phil&teds takes product safety and safe use seriously. We take the utmost care in designing products to meet or exceed safety standards all over the world.
We are extremely proud of our safety record, our proactive approach to product management, and our long term relationship with parents, all over the world. Sometimes, new concerns arise outside the testing and production framework that require immediate attention. We are proud to make positive, pro-active product improvement measures.
From time to time, we'll have a great idea to improve our products that may require an additional part or repair, modifications or replacement after the manufacturing process. In most cases, a simple (free) replacement part is all that's needed. If you have any concerns or questions please contact us or your retailer. We will be happy to respond.
At phil&teds safety comes first that's why we pride ourselves on attaining relative standards for all our products and keeping up to date with legislation in all our markets and complying. The main worldwide recognised standards are the British/European (BSEN), Australian/New Zealand (AS/NZS) and American (ASTM). We exceed these and product safety standards in all 50 countries that we operate in. Also proving our dedication to the cause we're the first and only juvenile hardware company to achieve full CPSIA compliance with the new CPSIA standard in the US - exciting stuff! - Check out our product compliance listing .
The following products have required such action:
|metoo highchair - free repair kit
|explorer / hammerhead strollers - frame upgrade
|sport V2 / classic V1 - hinge cover
|Dash Inline Buggy - handle mechanism (certain models)
|e3 sport V1 - hinge cover
In USA please refer to www.cpsc.gov for further details.
Consistent with our unwavering commitment to safety, and in conjunction with the U.S. Consumer Product Safety Commission, phil&teds USA is announcing a voluntary Recall to Repair of metoo clip-on highchairs sold after May 2006. This Recall is being conducted in response to reports that one or both table clamps have come free from a table or other surface, posing fall and amputation hazards to children. There have been 19 reported incidents, including two incidents involving sever and, in one case, permanent finger injury to children under 18-months old.
Safety is our first priority. You should stop using the metoo clip-on highchair immediately, and order a free repair kit that we are making available to metoo owners. Owners of chairs without plastic spacers will receive a repair kit consisting of new instructions, rubber clamp boots, and plastic spacers. Replacement Instructions are available to all customers on our website.
1. Order by phone: call phil&teds Customer Care at 1-855-652-9019 between the hours of 9am and 5pm Mountain Time; or
2. Order online: Click here to order online
To receive new user instructions, please visit our website at http://philandteds.com/en/instructions . phil&teds stresses that all users should read and adhere to the new instruction manual which contains valuable safety tips and service recommendations.
Should you have any questions please contact one of our trained customer service representatives at: 1-855-652-9019 or email@example.com Press Release
We're always seeking ways to improve the function and safety of products through our continuous innovation program, and when feasible to do so we make those improvements available to owners of older versions of the product.
We implemented the upgrade in production some months ago, creating 'Series 2' Explorer and Hammerhead buggies, and are undertaking an initiative to make the new brake available to owners of Series 1 (pre January 2011) Explorer and Hammerhead buggies, identifiable by serial numbers between 0610/0001(June 2010, unit number 1), and 0111/4788(January 2011, unit number 4788). The serial numbers are read as follows – MMYY/unit number
In cooperation with the CPSC and Health Canada, phil&teds, USA is announcing a recall of our explorer and hammerhead strollers. The brakes may fail on affected strollers, posing a risk of injury. This will involve, free of charge to all affected consumers, a new brake assembly.
Our solution is to replace the brake assembly with the upgraded 'Series 2' system. In the case of explorer owners phil&teds will send consumers a complete new frame fitted with a new brake assembly. Explorer consumers can perform an in-home swap out of the affected frame. For hammerhead consumers, phil&teds will provide a pre-paid return shipping carton so the stroller can be returned to phil&teds where the brake assembly will be replaced and the stroller returned to you.
Higher than normal warranty repair levels have been recorded in other countries, to Series 1 hammerhead and explorer strollers, and reports of users experiencing brake failure, which of course presents a potential safety risk. There have been no incidents reported in the USA or Canada.
We ask that you identify if your stroller is affected (see below). If it is, stop using the stroller immediately and request a free brake assembly upgrade by either:
NOTE: this only applies to pre-January-2011 explorers and hammerheads; it does not apply to newer explorers and hammerheads which already have the Series 2 brake; nor does it apply to any other model of phil&teds buggy.
Click here to register for your free frame upgradeCPSC and Health Canada joint release
Consistent with our unwavering commitment to safety we are providing consumers with notice of a voluntary recall to repair and upgrade the discontinued sport v2 and classic v1 strollers, manufactured between March 2008 and June 2010.
In cooperation with the U.S. Consumer Product Safety Commission, we are providing free of charge to all affected consumers a free self-fit hinge cover. This is in response to a very small number of reported cases of adult users catching a finger in the hinge mechanism of the sport v2 (which shares a hinge with the classic v1).
The voluntary recall to repair is to alert sport v2 and classic v1 owners of the possible risk of an amputation and laceration injury stemming from an adult user catching a finger in the hinge while folding or unfolding one of these strollers.
Of the phil&teds stroller range only these two strollers are affected by this recall. All other models have different hinge mechanisms.
Safety is our first priority and through this voluntary effort we urge consumers to immediately obtain and fit the free kit which may be obtained through one of the following methods:
Should you have any queries at all please feel free to contact one of our trained customer service representatives us on: 1-855-652-9019
phil&teds stresses that all users should read and adhere to the instruction manual which contains valuable safety tips and service recommendations.
Frame replacement - due to a small number of reports (one report too many!) of the apparent failure of the trigger actuated hinge lock mechanism to engage on one side, phil&teds have recalled all affected dash stock and replaced their frames. In the final step of this recall phil&teds are asking all dash buggy owners, for their own piece of mind, to make a final check of their frame. A buggy with a frame serial number CD0108/XXXX/XXXXX through to CD0808/XXXX/XXXXX will need a replacement frame - if you have one of these serial numbers click here to register your details (this will also show you how to find your serial number), or contact your retailer or distributor.
Some e3/sportv1 inline® buggy users are not using the folded frame-lock straps. In such cases, the buggy may unexpectedly unfold, causing the front part to flip forward. If this happens and the person also has their hand in the main hinge (in spite of the sticker on the frame warning against this), injury can result.
The hinge covers reduce the risk of injury when folding or unfolding your sport v1 or e3 buggy.
Important: you must NOT have a child in your buggy when folding it.
Safety is our first priority and through this voluntary effort we urge consumers to immediately obtain and fit the free kit which may be obtained through one of the following methods:
- read hinge cover instructions
Want to receive updates about new products and promotions?
© 2014 philandteds.com


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Bin collectionsDetails of when your bins are collected and what you can put in each bin.
Car parksDetails of car parks, charges and opening times
Council and democracyThe council offers a wide range of services to residents businesses and visitors.
Council Tax and benefitsOur Council Tax, Housing and Council Tax benefits and Business rates services are administered by Anglia Revenues Partnership (ARP)
HousingWe work to develop affordable housing, offer housing advice, homelessness prevention services, and manage the housing register.
Job vacancies and work experienceInformation about vacancies and working for St Edmundsbury Borough Council.
Online paymentsPay your council tax, business rates, invoices, housing benefits over payments and car parking fines online.
Planning and building controlPlanning consists of a number of formal processes that are used at different stages when making a decision and Building Control regulates the design and construction of buildings, making sure they meet the minimum standards set out in the Building Regulations.
West StowWalk in the footsteps of our Anglo-Saxon ancestors, explore their homes, see the evidence for yourself...
West Suffolk Housing Strategy consultationThis consultation has been extended and will close on 20 August 2014. Please share your views to help us improve the housing situation for current and future residents.
Forest Heath and St Edmundsbury councils are currently working on a joint draft Housing Strategy that sets out what we, together with our partners will be doing 2015-18 to improve the housing situation for our current and future residents.
These actions will directly contribute to the overall sense of community and wellbeing of West Suffolk.
This work needs to include enabling the supply of new housing; making the best use of existing housing; and offering support or specialist housing to those who require it.
Cashless car parkingPay for your parking over the phone
Changes to Housing Benefit and Council Tax Benefit in St EdmundsburyFrom 1 April 2013 changes will be made to the benefits provided through local councils.
Council TaxOur Council Tax, Housing and Council Tax benefits and Business rates services are administered by Anglia Revenues Partnership (ARP).
Council tax and financial informationOur Council Tax, Housing and Council Tax benefits and Business rates services are administered by Anglia Revenues Partnership (ARP).
Housing and Council Tax benefitsHousing and Council Tax Benefits services are run by Anglia Revenues Partnership (ARP) on behalf of St Edmundsbury Borough Council.
How to payDifferent ways to make payments
Parking fines and appealsIt is the responsibility of the user to make sure you ticket can be clearly seen on the windscreen.
Annual Canvass 2013The annual audit of all properties in St Edmundsbury will begin on 8 October 2013, to ensure that all eligible residents are included on the Register of Electors 2014. A form is being posted to every property in the borough asking for all occupants over or near to 18 years, to confirm their name , nationality and that the pre-printed address given is where they live. The form must be returned using the enclosed pre-paid addressed envelope.
Bulky itemsWe have a chargeable collection service for bulky household waste items such as furniture or white goods. Collections must be pre-arranged and paid for in advance of collection.
Business Rate reliefSmall rural businesses may be entitled to rate relief - check to see whether or not you are eligible.
Community development grantsGrants are available to help your community
Current vacanciesApply for a job at St Edmundsbury
Housing grantsGrants to help tackle specific problems with the condition of some private sector housing across West Suffolk include Decent Homes, Disabled Facilities, Empty Homes, Healthy homes and Thermal Comfort grants
Inspecting works and Completion CertificatesBy law, the Building Control Officer must be told when the work reaches each of the following stages.
Local land chargesLand and property based information service for prospective purchasers and developers.
Parking permitsThere are currently ten neighbourhood parking schemes in Bury St Edmunds and one in Haverhill.
Planning applicationsPlanning permission is generally required for the carrying out of any form of development which includes the change of use of land and buildings.
The borough council was one of the few district local authorities within the country to produce a Rural Action Plan to help deliver projects in our rural areas. These projects aimed to contribute to the preservation and enhancement of the social, economic and environmental well-being of rural St Edmundsbury.


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The ancient kingdom is in peril! Evil forces have corrupted the four elements and the waters of the altar of life have run dry. Unlock the four ancient books of magic, collect 16 mysterious cards and restore the kingdom to life. Match the enchanted symbols and set the kingdom free!
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The caller told police four people walked up to him near a gas pump and robbed him at gunpoint. The caller said the robbers drove away in a white four-door sedan.
California Highway Patrol officers arrested the men and women following a vehicle stop in Livermore.
Tracy police received 153 calls for service Monday. The following is a sampling of those calls.
2:24 a.m.: A woman said her boyfriend broke into her house on the 100 block of Carlton Way. She said she heard a window break and then saw him running away. Police are investigating.
7:02 a.m.: A catalytic converter was reported stolen on the 3300 block of Glenbriar Drive.
9:53 a.m.: A woman said someone wrote graffiti on her garage on the 100 block of Palm Circle.
11:43 a.m.: Police arrested a 30-year-old man for an outstanding San Joaquin County Sheriff's warrant following a disturbance at the Townhouse Motel, 607 W. 11th St. He was booked into San Joaquin County Jail.
4:51 p.m.: A business clerk told police someone had robbed Happy Cars Auto Care, 298 W. Grant Line Road, taking tools and wheels.
• This column includes a sample of items as reported in the Tracy Police Department dispatcher's daily log. Additional information is based on reports from officers and other law enforcement agencies. Charges may have been added or dropped as of press time, and all suspects are assumed innocent until proven guilty. To report information anonymously about a crime: Crime Stoppers, 831-6847.


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Syria's refugees, where will they go?28 Jan 2014 | 01:13
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News - Hong Kong - COURTS
Persecuted protected by customary international law, UNHCR says
Posted Mar 07th 2013, 12:00am by Joyce Man
... argues that the government must assess the applications itself rather than passing the responsibility to the UNHCR. "[The principle] is, at minimum, customary international law," Gerard McCoy SC, for the UNHCR, told the Court of Final Appeal. "The matter, we say, is simply beyond doubt." The UN agency said it seemed that the Hong Kong government wanted to contend ...http://www.scmp.com/news/hong-kong/article/1183828/persecuted-protected-customary-international-law-unhcr-says
News - Asia - AFGHANISTAN
Afghan refugees shiver at another deadly winter
Posted Jan 02nd 2013, 09:20pm by AFP
... decades, and the UN refugee agency UNHCR has co-ordinated efforts to reduce repeat fatalities. "Last year was the worst, and the weather is again turning bad," Sayed Ullah, 40, said as he lined up ... and I have no income except for just a bit of labouring work. We need help to get through the winter." UNHCR said it had funded and organised distribution of aid to more than 32,000 "internally ...http://www.scmp.com/news/asia/article/1118476/afghan-refugees-shiver-another-deadly-winter
News - World - AUSTRALIA
UNHCR 'concern' over Australia's handling of Sri Lankan refugees
Posted Jul 04th 2014, 09:44pm by AFP
... in Australian waters. Under its policy of not commenting on "operational matters", Canberra has refused to confirm the boats exist, sparking criticism from the UN refugee agency UNHCR. "UNHCR has followed with profound concern recent reports in the media and from the community in relation to the interception at sea of individuals who may be seeking Australia's ...http://www.scmp.com/news/world/article/1546699/unhcr-concern-over-australias-handling-sri-lankan-refugees
Comment - Insight & Opinion
UNHCR must decide its last refugee claims in Hong Kong
Posted Sep 24th 2013, 12:00am by ALETA MILLER
... Aleta Miller Aleta Miller says the transfer of work to HK officials will unfairly prolong process for some UNHCR must decide its last refugee claims With the announcement of a unified ... In this transition, the UNHCR has an obligation to be accountable to asylum seekers who have already undergone interviews and are awaiting a decision on their claim. Since 1979, the UNHCR has been deciding ...http://www.scmp.com/comment/insight-opinion/article/1316101/unhcr-must-decide-its-last-refugee-claims-hong-kong
News - Hong Kong - COURTS
Africans appeal ruling on refugees
Posted Mar 06th 2013, 12:00am by Joyce Man
... Joyce Man email@example.com Lawyers for the three men say the government has an obligation to handle the claims instead of passing them to the UNHCR to process Africans appeal ruling ... itself rather than passing the responsibility to the UNHCR. Lawyers for the men, who have not been identified by name, made their case at the Court of Final Appeal yesterday, after previous ...http://www.scmp.com/news/hong-kong/article/1180400/africans-appeal-ruling-refugees
News - Hong Kong - SOCIETY
UNHCR axes all aid for HK refugees in budget cuts
Posted Feb 27th 2013, 12:00am by John Carney
... John Carney firstname.lastname@example.com UNHCR axes all aid for HK refugees in budget cuts In a shock move, the Office of the United Nations High Commissioner for Refugees in Hong Kong (UNHCR) has announced that it will cut all financial aid to recognised refugees living here. There are 132 people with official refugee status in Hong Kong. Each one receives HK$500 from the UNHCR per month. ...http://www.scmp.com/news/hong-kong/article/1159313/unhcr-axes-all-aid-hk-refugees-budget-cuts
News - Hong Kong - ASYLUM
New UNHCR head urges Hong Kong to protect refugees and asylum seekers
Posted Dec 02nd 2012, 12:00am by JOANNA CHIU
... Joanna Chiu email@example.com Commissioner calls on city to do more, but authorities balk at possible risk of system abuse New UNHCR head urges HK to protect refugees The new head of the UNHCR in Hong Kong has made an unusually forceful call for the government to take responsibility for protecting refugees in the city. "There is no doubt that Hong Kong has the capacity ...http://www.scmp.com/news/hong-kong/article/1095267/new-unhcr-head-urges-hong-kong-protect-refugees-and-asylum-seekers
UNHCR vows to look into fate of Rohingya boatpeople
Posted Jan 09th 2011, 12:00am by Azizur Rahman, Ian Young
... Nations High Commissioner for Refugees pledged to look into the case. 'We are currently seeking more information through our networks,' said the UNHCR's Asia Bureau spokeswoman Ariane Rummery. If the 170 self-described Bangladeshis seek asylum in India, the UNHCR could do little for them, because India will not allow the UNHCR to assess asylum claims by people from ...http://www.scmp.com/article/735191/unhcr-vows-look-fate-rohingya-boatpeople
News - Asia - SRI LANKA
United Nations slams Sri Lanka for early deportation of asylum seekers
Posted Aug 04th 2014, 03:47am by AFP
... by deporting Afghan and Pakistan refugees before their asylum claims could be assessed. The United Nations High Commissioner for Refugees (UNHCR) said Sri Lankan authorities arrested 214 Afghan ... international obligations, the UNHCR said. "The UNHCR is dismayed by these actions of the government of Sri Lanka," the statement said. "The deportation goes against the principle ...http://www.scmp.com/news/asia/article/1565739/united-nations-slams-sri-lanka-early-deportation-asylum-seekers
News - Asia - MALAYSIA
Rights group urges Malaysia not to deport Uygur migrants to China
Posted Oct 06th 2014, 01:20pm by Agence France-Presse in Kuala Lumpur
... Commission for Refugees (UNHCR) on the matter. A UNHCR spokeswoman said the agency was still seeking information from authorities on the report of the 155 Uygurs and declined to comment. Malaysia deported six Uygurs in December 2012 while the UNHCR was processing their refugee claims, sparking an outcry. It deported an earlier batch of 11 Uygurs in 2011, saying they were involved ...http://www.scmp.com/news/asia/article/1610573/rights-group-urges-malaysia-not-deport-uygur-migrants-china
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The reward of great men is that, long after they have died, one is not quite sure that they are dead.
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Pierre-Jules Renard or Jules Renard (February 22, 1864- May 22, 1910) was a French author and member of the Acadmie Goncourt, most famous for the works Poil de Carotte (Carrot hair) (1894) and Les Histoires Naturelles (Natural Histories) (1896). Among his other works are Le Plaisir de rompre (The Pleasure of Breaking) (1898) and Huit jours la campagne (Eight Days in the Countryside) (1906).


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INGLEWOOD, Calif. (November 1, 2012)—The first Railbird Club – Presented by TVG – of Betfair Hollywood Park's Autumn meet will be Sunday, Nov. 11 and continue each Sunday throughout the 24-day season.
Hosted by popular TVG personality Rich Perloff, the Railbird Club, which begins at 7:30 a.m. and wraps at 9:30 a.m., offers an opportunity to watch morning workouts and includes a free continental breakfast at the Finish Line Cafe.
Copyright © 2009-2014, Hollywood Park. All rights reserved.


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INGLEWOOD, Calif. (August 23, 2010)—Hollywood Park stakes winners had a successful weekend at both Del Mar and Saratoga.
Clearly the front runner to be the champion 3-year-old filly, Blind Luck became the first winner of the Hollywood Starlet to capture the Alabama Stakes, winning the Grade 1 by a neck.
The victory was the ninth – five coming in Grade 1's – in 13 starts for Blind Luck, who is owned by Peter Abruzzo, John Carver, Mark DeDomenico and trainer Jerry Hollendorfer. The daughter of Pollard's Vision was able to rally from last in the 1 ¼ mile race despite the extremely slow pace.
If Blind Luck is at the head of her class, Evening Jewel is certainly a close second. The talented California bred, who won the Honeymoon Handicap in her turf debut on May 31 at Hollywood Park, remained undefeated on the surface Saturday.
Owned by the Braly Family Trust and trained by Jim Cassidy, the Northern Afleet filly defeated American Oaks winner Harmonious by a half-length in the $300,000 Del Mar Oaks. The Grade I victory was her third in a row on grass. Overall, Evening Jewel, who finished a nose behind Blind Luck in the Kentucky Oaks on April 30, has won six of 12 and earned $876,943.
Victor Espinoza was aboard Evening Jewel and he was also the rider for Sweet August Moon, who made it consecutive graded stakes wins Sunday. Trained by Brian Koriner for Peter and Evelyn Parrella's Legacy Ranch and Team MacPherson, Sweet August Moon defeated Alpha Kitten by three-quarters of a length in the $147,000 Rancho Bernardo Handicap at Del Mar. This race came five weeks after the 5-year-old Malibu Moon mare had won the A Gleam Handicap at Hollywood Park.
A winner of seven of 17 with a bankroll of $426,396, Sweet August Moon earned a berth in the Breeders' Cup Filly and Mare Sprint on Nov. 5 at Churchill Downs by virtue of her Rancho Bernardo score.
Copyright © 2009-2014, Hollywood Park. All rights reserved.


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Where can I get information regarding my professional license?
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Item #15813
Our Deluxe Chaise Box-Edge Outdoor Chair Cushion features double welting and a luxuriously plush foam fill. This thick 4" outdoor replacement cushion is available in a variety of Sunbrella®, Outdura® and polyester fabrics. Sunbrella® and Outdura® are 100% solution-dyed acrylics. All our fabric options are resistant to UV rays, stains and mildew for long life and lasting color. Coordinate your outdoor seating with our outdoor market umbrellas, curtains, throw pillows and poufs.
Product Details
Home Decorators Collection
4675 East Liberty St.
Mexico, MO 65265-9804
Box-Edge Rectangular Outdoor Chair Cushion
$26.99 - 59
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Box-Edge Deep Seating Outdoor Chair Cushion
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Box-Edge Deluxe Chaise Outdoor Cushion
$129 - 194
Box-Edge Seat/Back Outdoor Chair Cushion
$74 - 115
Box-Edge Contoured Outdoor Chair Cushion
$25.99 - 55
Portillo 5-Piece Seating Set
Was: $1199
Now: $598.99
Martingale 5-Piece Outdoor Dining Set
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At the Global Summit of Women in Athens, Michael Halbye, Regional Leader, Europe Middle East & Africa at McKinsey & Co shared the latest information on 5 key Global Megatrends.
Via Kenneth Mikkelsen
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Gary Bamford's curator insight, October 14, 2:58 AM
Love the 5-monkeys slides - make sure you view them ;)
Ian Berry's curator insight, October 14, 11:26 PM
I have a different view I believe innovation feasts on culture as much as the vice-versa
The Governance Advisory Practice's curator insight, October 15, 4:57 AM
You can have the best talent, best ideas, best processes, abundance of cash. If your culture does not align, being successful with innovating starts looking as if it's a matter of luck.
Matthew Farmer's curator insight, October 20, 1:49 AM
....so it not just that leaders need to need to change but businesses and organizations as well. 21st century leaders need to understand how these shifts (or the Big Shift as Hagel talks about it) are going to manifest themselves so they can either 'lead the change' or 'understand the changing context in which they must lead'. Quite possibly both!
Kenneth Mikkelsen's curator insight, October 19, 7:14 PM
The content in this presentation will be included in a new book by Dave. Meanwhile, you can follow Dave on Twitter here: @davegray.
I also strongly encourage you to read Dave and Thomas Vander Val's latest book, The Connected Company.
Karine Mangion's curator insight, October 20, 6:09 AM
Applying Agile principles to academia, a possible way-forward in a fast changing and competitive environment.
Kenneth Mikkelsen's curator insight, October 14, 6:40 PM
For this study, Forbes Insights, in association with KPMG, surveyed 910 executives at U.S.-based multinationals and banking or asset management firms. Out of 709 corporations, 90% of executives came from companies with revenues over $1 billion. Out of 201 banking or asset management firms, all had assets under management of at least $5 billion.
Steve Bax's curator insight, October 15, 5:26 AM
Another very good scoop from Kenneth Mikkelsen here. Key 'take aways' for me are the reinforcement of some of the core principles of effective change within organisations. The research identifies the importance of elements such as: alignment of corporate culture, structure and early integration of metrics to the process. Although the shift is clearly to emergent rather than planned 'seismic' Kurt Lewin type change, the need for John Kotter's eight steps can still be seen in the issues from this recent study. There are some valuable findings on culture, decentralised companies and the need for collaboration across functions here too.


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MegaGlest is an open source 3D-real-time strategy game, where you control the armies of one of seven different factions: Tech, Magic, Egyptians, Indians, Norsemen, Persian or Romans. The game is setup in one of 14 naturally looking settings, which are crafted with great appreciation for detail. Additional game data can be downloaded from within the game at no cost.


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8261 Rivers Ave,
North Charleston, SC 29406
"You've Got a Friend in the Car Business"
At Subaru of Charleston you will experience the world class service of a knowledgeable and experienced staff. We are committed to your satisfaction and strive to exceed our customers' expectations. We are the greater Charleston Subaru dealer with the inventory and price to get you into your dream car today. We've served hundreds of customers from Charleston, Mount Pleasant, Hanahan, Summerville and West Ashley. Set up a test drive by contacting our friendly sales staff or submitting a short form on our inventory details pages.
If you live in Charleston and are searching for a new vehicle, it will be worth your while to come take a look around our lot at some new 2014 and 2015 Subaru models including the:
Outback, Legacy, Forester, Impreza, WRX, BRZ and XV Crosstrek
Its hard to beat the performance and value you can find in a new Subaru from our dealership. With excellent gas mileage, symmetrical all-wheel drive and impressive features, we are sure you will be impressed once you take one out for a test drive. Add that to the superior service our Charleston Subaru dealership prides itself on, and you will be happy you came to see us. We are located at 8261 Rivers Ave North Charleston, SC and would be happy to chat with you.
For high quality used car for sale, come visit Crews Subaru of Charleston. We are always bringing in used cars on trade-in, so we have one of the largest selections of used cars in the Charleston area. Every used vehicle we take in trade undergoes an extensive inspection to ensure it will run like new for years to come, or we don't sell it. If you have been searching for a specific used vehicle, take a second to complete our Car Finder form and we will notify you when a matching car arrives at our dealership.
Subaru of Charleston offers a variety of automotive services at one convenient location. Are you wondering how you are going to pay for your new vehicle purchase? Visit our finance department where our financial professionals will review the various car loan and lease options that are available on the vehicle you are interested in purchasing. By working with a variety of financial institutions, we are the Subaru dealer that will get you a low interest car loan in the Charleston area. Take a moment to complete our online auto finance application to see if you are pre-approved.
Our greater Charleston Subaru service and car repair center has the resources to make your vehicle run as well as it did the day you drove it off the lot. Subaru of Charleston's skilled mechanics have spent years working on Subaru vehicles and will properly diagnose problem. Subaru of Charleston also offers car parts to the Charleston area so that you can maintain your vehicle. Our genuine Subaru car parts will keep your vehicle in top condition for many years to come.
Easily schedule auto repair or Subaru service by submitting our online service appointment form.
As you can see from the above, Subaru of Charleston is a full-service greater Charleston new and used car dealership. We're dedicated to providing the best service possible, and will assist you through the purchasing process any way we can. Stop by our dealership to learn more about us, we are located at 8261 Rivers Ave North Charleston, SC, or give us a call, our local number is and talk with a member of our sales team. about us. We are a short drive from West Ashley, Mount Pleasant, Hanahan and Summerville areas.


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HOME Logo Gear Gear Logo Gear T-Shirts Logo Gear T-Shirts Short Sleeved $40 to $60 Product ID: 1125873
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Get ready for an incredible display of NBA talent! The 2013 NBA All-Star Game is in Houston this year, and it'd be a shame to miss an action-packed competition between the top players from the NBA East and West. Show your support in NBA All-Star style with this Gametime Shooter T-shirt from adidas. With printed All-Star graphics, an adidas logo and contrast color details, this V-neck tee will get you ready to cheer harder than ever for your favorite NBA superstars!
- 100% Polyester fabric
- Contrast color details
- Imported
- Lightweight V-neck T-shirt
- Officially licensed NBA product
- Screen print graphics
- Tagless collar
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Special event items are produced by manufacturers only after the outcome of a game or event. These are advanced sale items and will ship immediately after they are received in our warehouse.
Manufacturer direct items are shipped directly from the manufacturer. These items are not available for international or expedited shipping.
Customized items can be personalized with options such as your name, your favorite number, and/or designs. Some options may be limited by league rules.


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Ghana Must Go – Aug 1, 2013— Aug 1, 2013 | Leave a comment
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MondayEbola: What Is The Risk Of Catching It On A Flight? by By Jon Kellyn Oct 20th | No Comments
People who flew on a plane with a Texas nurse on the day before she came down with symptoms of Ebola are being tracked down by public health officials. What…
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TuesdayJonathan, Desperation And The Chibok Girls' Debacle by Comrade Timi Frank Oct 21st | No Comments
The stunt pulled that the 219 abducted Chibok girls would soon be released after over six months in Boko Haram captivity may well represent a new phase of desperation by…
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WednesdayThe Greatest by Hannatu Musawa Oct 22nd | No Comments
News that Muhammed Ali's battle with the incapacitating disease, Parkinsons, has reached a point where he is unable to speak is not shocking but still, so, so heartbreaking.At the…
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ThursdayThe Shape Of Things To Come by Abba Mahmood Oct 23rd | No Comments
Gradually, the political terrain and picture is becoming clearer. President Jonathan is the "sole" candidate "adopted" and "endorsed" by the ruling Peoples Democratic Party (PDP) hierarchy to contest the 2015…
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FridayOBJ: Gritty Maverick Takes Centre Stage Again! by Garba Deen Muhammad, Guest Column Oct 17th | No Comments
As a habit, the only virtue former President Olusegun Obasajo's critics will grudgingly concede to him is his matchless love for his country, his obsessive patriotism that set him apart…
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SaturdayFlying The Falcon 2000S by Capt. Daniel Omale Oct 18th | No Comments
Although 20% larger than typical super midsize (SMS) business jets, the new Falcon 2000S is designed and priced to compete in that market. It can fly six passengers 3,350nm at…
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SundayAmbassadors Of Mischief by Aniebo Nwamu Oct 19th | No Comments
Perhaps, the presumed talks with Boko Haram and the publicised truce on Friday were a hoax after all. Were it not so, the abducted Chibok schoolgirls would have been freed…


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When scours, malnutrition and disease threaten a calf's life, and other remedies are not enough, now there's Last Stand with ImmWave. ImmWave is a no Read More
When scours, malnutrition and disease threaten a calf's life, and other remedies are not enough, now there's Last Stand with ImmWave.
ImmWave is a novel technology containing select milk proteins designed to give an immediate boost to the calf's immune system enabling a critically ill calf to battle life-threatening pathogens that can lead to death. With the addition of ImmWave, Last Stand is a powerful lifesaver for calves critically ill with scours and malnutrition.
The multi-faceted formulation also contains Encrypt®, multiple targeted egg proteins, host-specific micro-encapsulated lactic acid producing bacteria, Vitamin B complex and Vitamin D3 making Last Stand with ImmWave a wise choice in the battle to save every calf, improve productivity, and increase profitability.
Last Stand with ImmWave is recommended for use in beef and dairy calves suffering from scours and malnutrition. It comes in a convenient 60 g, single dose tube. Simply administer entire contents of tube orally. Repeat as needed. Not recommended to exceed three consecutive days for each event. No withdrawal necessary.
Visit the manufacturer's website for more information.
Reviews (1)
"Life Saver!!!"
"This product works when you think there's no hope left. Gives calves an appetite, clears up scours within the day, and perks them up almost immediately. Gave it to a month-early calf who wouldn't eat and couldn't stand (under 30 pounds!)- and she was up and eating within hours, and thrived despite a VERY rocky start. This product is part of my standard regimen for ""rescue"" calves picked up from local dairies when the farmers don't want them because they're failing. It's seems a little expensive, but not when you see what it can do!"


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Showing 1-8 of 8 items found in Events
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7th Annual Christie Clinic Illinois Marathon
The annual Christie Clinic Illinois Marathon is one of the most popular spring running events in the Midwest… and, arguably, the country with its fast and flat course, ideal for qualifying for the Boston Marathon. With over 20,000 participants expected in the 5K, 10K, half marathon, marathon, relay and the youth run, the Illinois Marathon is a destination race for people from all over! From flat and fast courses to the Memorial Stadium 50-yard line finish to the rockin' State Farm 27th Mile Celebrate Victory Bash, this has all the makings for the perfect spring getaway. 217-351-4133
CITY: Champaign
Parade of Lights
Join the Champaign Center Partnership as they officially launch the holiday season with a Parade of Lights. Marching bands and lighted floats weave their way through the streets of Downtown Champaign with Santa making his grand appearance just in time to light the City Christmas Tree.
CITY: Champaign
C-U Comedy Festival
Nothing beats a good laugh. The kind you let out when something hilarious happens. Get your fill of laughs October 22-25 at the first C-U Comedy Festival, held at a variety of locations including Champaign's infamous Memphis on Main and Urbana's iconic Canopy Club. This laugh-fest will feature local comedians as well has headliners from St. Louis and Chicago!
CITY: Champaign
32nd Annual Country Christmas Craft Show
Hosted by Gifford State Bank, this annual Christmas Craft Show brings together over 500 vendors and 8,000 shoppers! This event offers two days of "shop til ya drop" fun so you can find that perfect gift for everyone on your list. Parking is free and admission is just a $1 donation to Country Health Auxilary.
CITY: Gifford
Lunch with Santa on Train
Come out for Lunch with Santa on the Train at the Wabash Depot in Monticello, Illinois, a holiday favorite for kids of all ages. Enjoy a train ride, individual visit with Santa, and kid friendly sack lunch. The ride is about 60 minutes per trip. Reservations Recommended.
CITY: Monticello
The Polar Express at Monticello Railway Museum
Held at Monticello Railway Museum. Read along with the story as the train makes its round-trip journey to the North Pole. Meet Santa and enjoy caroling, hot chocolate, surprises and a treat. And, for those who believe, a special gift for each child. Children are encouraged to wear their pajamas! Nov 14-15, Nov 21-22, Nov 28-30 & Dec 5-6.
CITY: Monticello
Allerton Park Trail Run
The run is a 5.7 mile trail run (and 2 mile untimed walk) held on the estate of Robert Allerton Park in Monticello, IL. The time of year, Allerton is beautiful as the trail is through fall-colored forests and past the unique gardens and statuary of Allerton Park.
CITY: Monticello
16th Annual Rattlesnake Master Run for the Prairie
The 5K fun run and walk will traverse Meadowbrook Park one and a half times before returning to the finish line.
CITY: Urbana
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The company was started by Italian designers Domenico Dolce (born 13 September 1958 in Polizzi Generosa, Sicily) and Stefano Gabbana (born 14 November 1962 in Venice). By 2005 their turnover was €597 million.[2] The two met in Milano in 1980 and worked for the same fashion house. In 1982 they established a designer consulting studio. In time it grew to become "Dolce & Gabbana". They presented their first women's collection in 1985[3] in Milan, where a year later their store would open its doors in 1986 (Dolce & Gabbana 2011).
Two years later they launched their leotard line and in 1989 started designing underwear and swimming costumes (Domenico). Dolce and Gabbana started to export their products in Japan and other countries like the U.S. where they found their own showroom in 1990 (Gabbana, Stephano 2011). The same year they showed their men's collections. They launched their first perfume Dolce & Gabbana in 1992 (Dolce & Gabbana 2011). They won the Woolmark award in 1991 and the prize "most feminine flavor of the year" in 1993 (Dolce & Gabbana 2007). They won an Oscar for best male perfume in 1996. Towards the end of the 1990s their sales were around 500 million dollars and in 2003 alone their revenue reached 633.2 million dollars (Gabbana, Stephano 2011). From Wikipedia
This product is backed by a full 30 return policy. If for any reason you are unhappy about this product, you have a full 30 day to return it for a full refund. (Does not include shipping fees)
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Main Content
Dale Earnhardt Jr. will have 600 miles of Charlotte Motor Speedway to conquer when he pilots the No. 88 National Guard Chevrolet SS in the longest race of the season! This patriotic, multicam paint-out is scheduled to run at the Coca-Cola 600 on May 26. The National Guard is comprised of approximately 358,000 Citizen Soldiers and on any given day more than 255 National Guard Soldiers are aiding their community on emergency response missions. These soldiers hold civilian jobs or attend college and are actively ready to defend America in the event of an emergency! Race fans do not want to miss this one-of-a-kind Action Racing Collectibles 1:24 scale platinum die-cast of the No. 88 National Guard Chevy SS running Memorial Day Weekend. Designed to replicate the brand new Generation 6 stock body, each die-cast is authentically detailed and officially licensed by NASCAR.
- 1:24 Scale replica die-cast car
- High-quality graphics
- Measures approximately 8" long
- Officially licensed NASCAR product
Special event items are produced by manufacturers only after the outcome of a game or event. These are advanced sale items and will ship immediately after they are received in our warehouse.
Manufacturer direct items are shipped directly from the manufacturer. These items are not available for international or expedited shipping.
Customized items can be personalized with options such as your name, your favorite number, and/or designs. Some options may be limited by league rules.


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Hotel Villarreal
Hotel Villarreal, is situated in Valencia city centre, ideally located next to a metro station.
We have 29 air-conditioned rooms complete with bath. Two rooms feature a terrace and extra beds are available on request. All the rooms are equipped with:
- Minibar.
- Telephone.
- Hairdryer in your private bathroom.
- Locks with opening card.
- Radio
-Safety box.
Free Wi-Fi service available with high quality line. Private parking available too, for 10 euro extra charge per day.
Breakfast is served every morning in our Bar for an affordable extra charge: Continental Breakfast is 4 Euro per person/day; Buffet Breakfast is 7 Euro per person/day.
While staying at Hotel Villarreal you can enjoy visits to the city museums and discover the varied ancient and modern architecture at such attractions as: Las Torres de Serrano, La Lonja de la Seda, the Cathedral, La basilica, El Palau de las Artes Reina Sofia;La Ciudad de las Artes y Ciencias.
Please note:
Check in: 12 pm.
Check out: 12 pm.
Breakfast is not included, but served for an extra charge.
Credit Cards payment accepted.
Our Cancellation Policy is 72 hours in advance.
Availability & RatesTo view availability and prices please select dates and click 'Update Dates'
B&B Facilities & Policies
- Air Conditioning
- Airport transfers
- Bicycle hire
- Ceiling fan
- Cots available
- Elevator
- Free Parking
- Free Wifi
- Hair Dryers
- Laundry Facilities
- Parking
Cancellation PolicyThis property has a 3 day cancellation policy. Failure to cancel within this time will result in a cancellation charge equal to the first night of your stay.
DirectionsShow MapHide Map
Take the Metro Line Green /line 5) to Angel Guimer Stop. Leave the train station and you will be already in our street. Walk along this street. The hotel is a white building in the corner,


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Thursday, April 18, 2013
12:15pm – 12:45pm
Adolphus Busch Hall, 29 Kirkland Street, Cambridge, MA 02138
Midday Organ Recital: Angela Kraft Cross
Angela Kraft Cross, Organist, Congregational Church of San Mateo (UCC), San Mateo, CA, and Staff Organist, California Palace of the Legion of Honor, San Francisco, CA
Recitals are performed on Harvard's famous 1958 D. A. Flentrop organ. Audience members are invited to lunch quietly while listening.
Free admission
Presented by the Harvard Organ Society in collaboration with the Harvard Art Museums and the Memorial Church.