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Stranger, you aimed for adsblacklist.com, but langed on this page. What happened?
I stumbled upon www.adsblacklist.com a while ago when it was already down for maintenance. Later, the domain became vacated. So I was never able to use it myself.
As someone who does ad optimization for his own and clients websites, I am still intrigued by using the ad and category filter to improve AdSense performance.
What was adsblacklist.com all about?
Adsblacklist.com provided a list of MFA (Made for AdSense) or LCPC (Low Cost per Click) sites that delivered low paid ads through AdSense to your site. You could then import this list into your AdSense account in order to block the ads. As a result, you could increase your AdSense earnings.
Just an example:
Imagine you have 1,000 clicks per day and a CPC (cost per click) of $0,02. Increasing the CPC to just $0,04 would double your income and result in an extra $20 per day.
The community on adsblacklist.com reviewed thousands of such urls and the success stories I read really made my believe that it made an impact to block them.
How can I detect low paying ads?
Adsblacklist.com was a community site where everyone could submit a url of a low paying advertiser and have it been reviewed by other users. Even though the community doesn't exist, you can still detect and block low paying ads manually.
The explanation comes from Emir Pilavdzic, the original founder of adsblacklist.com.
If you are a webmaster running Adsense on your own website, you've probably seen google ads with text like "We have found 4 best products for …", or "Best resources on net for …". Well in most cases, these advertisers pay you only between $0.01 to $0.03 per click, depending on your site PR (Page Rank), traffic and page views. So detecting them is very simple. If you visit them (DO NOT CLICK ON YOUR OWN ADS) and see more ads than content, then you certanly got a winner.
What will happen with adsblacklist.com?
I just decided to purchase this domain and don't know yet what I am going to do with it. It is very likely that I am going to create a service or tool of some kind, but not take the approach with a forum like it was originally on adsblacklist.com.
I am definitely going to dig deeper into the topic of blocking urls in AdSense and also write about my tests and findings.
In order to not miss it, I would ask you to subscribe to the newsletter. If you have an idea then just comment below or contact me.


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The Witcher is RPG for the PC developed by CD Projekt RED STUDIO and originally released in 2007. The game tells the story of Geralt of Rivia, who at the opening of the game is tasked to cure the daughter of King Foltest of a curse which causes her to transform into a feral monster. [Info from Wikipedia]
The Witcher Outcast was a planned add-on that was in development by roXidy, a Canadian group which previously created the Neverwinter Nights: Wyvern Crown of Cormyr premium module for BioWare.
Outcast was going to be released as DLC in most countries and have a disc release in some countries, like Poland and Russia. It was in development from late 2007 until around mid-2008, when it was canceled by CD Projekt.
The draft of the story for this add-on can be read below:
The story takes place in the early part of Geralt's life, before he is established as a Witcher, during the reign of King Videmont of Aedirn (around 1190). It takes place in the Skellige Isles off the west coast, on an island ruled by jarl Harald. Many years ago, a monster attacked Harald's pregnant wife Morganna. In return, Harald went out to slay the monster, with the help of the gnome Shiltzen. As payment, Shiltzen demanded Harald's firstborn, but when Morganna gave birth, she bore twins. Seeing that the second child was monstrous, Harald gave that child to Shiltzen instead of the firstborn Astrid.
The full design doc can be downloaded from GameBanshee!

subset: commoncrawl


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© 2024 MJH Life Sciences™ and Pharmaceutical Technology. All rights reserved.
IQ Consortium representatives explore and define common industry approaches and practices for applying GMPs in early development.
The authors, part of the International Consortium on Innovation and Quality in Pharmaceutical Development (IQ Consortium), explore and define common industry approaches and practices when applying GMPs in early development. A working group of the consortium aims to develop a set of recommendations that can help the industry identify opportunities to improve lead time to first-in-human studies and reduce development costs while maintaining required quality standards and ensuring patient safety. This article is the fifth paper in the series and focuses on specifications.
The International Consortium on Innovation and Quality in Pharmaceutical Development (IQ Consortium) was formed in 2010 as an association of over 25 pharmaceutical and biotechnology companies with a mission to advance science-based and scientifically-driven standards and regulations for medicinal products worldwide. In previous issues of Pharmaceutical Technology, papers written by the IQ Consortium's "GMPs in Early Development Working Group" described the desire and rationale for more clear and consolidated recommendations for Good Manufacturing Practices (GMPs) in Early Development (Phase 1 through Phase 2a) (1–4). In this issue of Pharmaceutical Technology, the IQ Consortium presents a proposal for the analytical assessment and control of both drug substances (DS) and drug products (DP) in early development specifications. These recommendations take into consideration the differences in clinical trials in early development versus those in later development and provide a starting point to stimulate discussion on specifications in early development.
Previous industry position(s) on the topic of science-based specifications have not addressed early development needs or differentiated the role of specifications in early versus late development (5). During preclinical and early development, the primary focus is to progress the product into the clinic for safety and preliminary efficacy assessment. Due to the high attrition rate in early development, consistent specifications that ensure patient safety are desirable. During late development, specifications evolve as the clinical focus expands from safety to include efficacy, and as the product and corresponding synthetic and formulation process undergo significant transformations (e.g., synthetic route changes during scale-up, evolution of dosage forms from fit-for-purpose to robust formulations and processes suitable for commercial manufacturing). Therefore, early development specifications should also focus on those tests and acceptance criteria determined to be critical for the control of product quality with an emphasis on patient safety and supported by preclinical and early clinical safety studies.
Based on the cumulative industry experience of the members of this IQ working group, the authors of this paper have proposed standardized early phase specification tests and acceptance criteria for both DS and DP, which are discussed herein. In addition to release and stability tests, consideration is given to internal tests and acceptance criteria that are not normally part of formal specifications. These tests can be performed to collect information for product and process understanding, or to allow for tighter control (i.e., target criteria tighter than the release testing criteria), to ensure product quality will be maintained throughout the product's retest period. Based on the information obtained in early development, additional tests and acceptance criteria for other attributes (e.g., water content) can be included as the late development focus shifts to process and product performance and consistency; eventually aligning with the available ICH guidelines (6).
The scope of this position paper has purposely been limited to traditional small molecules that are formulated into solid oral dosage forms intended for US regulatory filings with the desire to build consistency across all worldwide regulatory regions. However, it is believed that the concepts presented can be easily adapted to other dosage forms and routes of administration. Although designed as an industry proposal, it is recognized that each company needs to evaluate these DS and DP specification recommendations based on their individual business needs.
The DS used in the first-in-human (FIH) enabling GLP drug safety studies, referred to in this article as the "tox batch," is a fundamental part of the product lifecycle in defining the specifications for an early phase clinical DS. For the DS used in the tox batch, internal targets rather than formal specifications are routinely used while gathering knowledge about impurities, structural identification, process purging capabilities, rework processing procedures, and potential impact to the safety study. The DS tox batch is typically subjected to a series of tests to confirm description, identity, potency, and purity. The main goals are to:
For DS intended for clinical studies, additional testing and controls beyond those used for the GLP toxicology lot testing may be required. The testing may be similar to the DS tox batch, but with established acceptance criteria. In early development, the depth of knowledge regarding the synthetic route is still evolving and the DS has not been fully characterized. Accordingly, the initial clinical acceptance criteria are often based on target specifications (see Table I), with the safety limits established from the tox batch being evaluated during the disposition process of the GMP clinical DS. If the tox batch is also inten
ded to be used in a clinical study, there is an advantage in that the qualification of impurities for the clinical studies is inherently assured. In this case, the formal specification for clinical disposition of the DS may be established based on the results of tox batch testing. To further highlight the differences in expectations for early phase DS specifications, the authors propose a standardized set of clinical DS specification attributes in the following sections.
Description. Description, or appearance, is a test describing the visual attributes of the DS. Although technically simple in terms of the test, it can be the subject of much discussion due to potential discrepancies in visual observations from analyst to analyst. Important aspects of this specification are to ensure that there is no visible contamination or anomalous appearance within the DS. The recommended early phase acceptance criteria is often a somewhat broad range of colors (e.g., "white to almost-white to light yellow powder") because there is typically little batch history in early development related to the color of the DS. If it is known that the DS has an inherent color, the specification should be adjusted accordingly.
Identification. At least one form of discerning chemical identification (ID) testing is performed in the early clinical release DS specifications. This testing ensures that the drug being dosed is traceable to the same chemical entity that was qualified in the safety studies. A single ID test by a spectroscopic method such as IR is often employed. Often, the spectroscopic method compares the DS with a known batch that has been well characterized by several analytical methods.
Counterion. The counterion, if present, often is a relatively large percentage of the DS and as such is important to understand the overall potency. The recommended acceptance criteria is "report results" while batch data is accumulated and the variability of the analytical methods is assessed. If the DS is sensitive to extreme counterion levels (e.g., changes in hygroscopicity), internal targets may be implemented to prospectively alert the internal product development team of any potential issues.
Assay. Assay is a critical DS component used to determine the accurate dosing concentration for the corresponding clinical DP. The recommended range is 97.0% to 103.0% (wt/wt on a corrected anhydrous basis) based on typical assay variability for an HPLC-UV method and an acceptable accuracy range required for the early phase clinical studies. This range may be modified with justification for particular circumstances that require a wider acceptance range (e.g., elevated levels of a qualified impurity). In the absence of a reference standard, which may be the case for the initial DS lot, the assay value may be derived by using an assigned chemical potency factor that takes into account related substances, residual solvents, moisture, counterion, and inorganic impurities present.
Impurities and degradation products. Controlling organic impurities and degradation products through the DS specification is required during all stages of drug development, except in initial microdose studies. As discussed, understanding the profile of impurities qualified in the Tox batch is crucial to establishing acceptance criteria for impurities in early phase clinical DS. It is also important to monitor degradation products and impurities present in the clinical DS which may not have been qualified in toxicology studies.
In early phase development, there is limited exposure to the clinical candidate and low numbers of individuals participate in these early clinical studies. The risk to patient safety is relatively low compared to late stage development (7, 8). Therefore, this IQ working group proposes controlling impurities in early stage DS at levels that are three times (3X) higher than those defined in ICH Q3 guidelines (9, 10). As clarified in the preamble of these guidance documents, the ICH impurity guidelines are intended for pharmaceuticals approaching the point of final commercial application submission. It is inappropriate to apply these commercial ICH expectations during early clinical development based on the shorter duration of exposure during these earlier clinical studies. This 3X ICH recommendation for DS impurities in early development translates to a qualification threshold for individual impurities being three times the commercial ICH Q3A limit. Specifically, the early phase DS impurity qualification threshold is proposed to be 0.5% or 3 mg per day intake, whichever is lower, for a maximum daily dose ≤ 2 g/day. It is recognized that individual companies within industry may choose to apply different impurity qualification thresholds in early development based on an assessment of safety in the context of the individual development program.
Similarly, an identification (ID) threshold of three times the ICH Q3A limit (0.3%) is proposed for unknown impurities that have not been qualified by toxicology studies. This ID threshold can be set higher for unknown impurities that have already been qualified. It is expected that as development progresses, impurities would be assessed from a toxicological perspective, appropriately qualified as necessary, and the relevant specifications updated accordingly. Later in development (Phase 2b and beyond), when a larger patient population is exposed to the clinical candidate for longer durations of time, the DS specifications for unqualified impurities should be narrowed to approach the limits outlined in the commercial ICH guidelines. Table II provides examples of various impurity scenarios to illustrate the utilization of the proposed early clinical identification and qualification thresholds and their potential impact on the acceptability of several example DS lots. All of the included examples assume a maximum daily dose of < 2 g/day and that the individual impurities are nongenotoxic.
For individual impurities that exceed the 0.5% threshold but are supported by toxicology data, an upper limit of not more than (NMT) 1.0% in the DS is appropriate for this stage of development. In some situations, an upper limit greater than 1.0% can be justified if the impurities are qualified at a higher level or if it is evident that the specific compound is also a known metabolite. In either case, a close review of the impurity profiles is required to ensure the quality of the clinical lot(s) is appropriate for the intended use and comparable based on projected exposure levels to the tox lot impurity profile. This may be triggered through the use of internal targets with alerts corresponding to the identification or qualification levels discussed above. For total impurities, the acceptance criterion often correlates with what is known about the individual impurities. An upper limit of 3.0% for total impurities is proposed as suitable for this stage of development. However, a higher upper limit for total impurities may be justified if there are a number of qualified impurities present in the DS.
Chiral impurities. Chiral impurities are usually held to the same criteria as any other impurity or degradation product with a known structural identification, leading to a proposed specification of NMT 1.0%. However, the target limit for the minor enantiomer can vary based on understanding of its pharmacological activity, toxicological qualification, metabolism pathway, and purging capabilities of the synthetic process. Sometimes it is difficult to determine the absolute chiral purity of a DS that has multiple chiral centers due to chromatographic separation challenges. For these molecules, specific rotation can be used to monitor the chiral purity in early as well as late development. Another acceptable approach to controlling chiral impurities in the DS is to monitor the chiral purity of the starting material or at an intermediate stage, where the corresponding isomers can be readily prepared and chiral chromatographic methods developed.
Residual solvents. The early development specifications for residual-solvent control are often set using the ICH established limits, including the consideration of maximum daily dose for Class 2 solvents (Option 2) (11). If the residual-solvent levels are likely to exceed the ICH limits, the specification limits in early development may be set higher than these ICH limits if they are realistically based on the manufacturing process capabilities and if there is low toxicity potential (e.g., Class 3 solvents that form solvates with the DS). In lieu of setting the standard ICH acceptance criteria, evaluation of known safety data are normally provided and justified by the appropriate drug-safety organization. It is also common practice to only set acceptance criteria on non-Class I solvents used in later steps of the synthetic process (e.g., final recrystallization and last synthetic steps) while assuring all solvents are purged through internal/characterization testing of intermediates and/or final DS.
In addition to the specification tests already described, there are several tests routinely performed but not included in the specifications that are designed to gather information on the DS as the compound advances through process and analytical development. These tests are often linked to process consistency, and in early phase development there is sometimes a temptation to set wide limits based on limited manufacturing experience. Instead, it is recommended to gather data through internal/characterization testing as manufacturing experience is gained. These tests may become part of the formal specifications when meaningful limits can be introduced based on experience with the compound. These additional characterization tests are discussed below.
Potential mutagenic impurities. Limits for mutagenic or potentially mutagenic impurities have been the subject of much discussion among the industry because ICH is currently drafting its M7 guideline on this topic (12). While the landscape for this class of impurities continues to evolve, the recommendation is to follow existing guidances, such as the 2007 CHMP Guideline on the Limits of Genotoxic Impurities, until ICH M7 is finalized (13).
Inorganic impurities. Inorganic impurities are typically monitored via Residue on Ignition (ROI) and heavy metals tests using US Pharmacopeia (USP) General Chapters <281> and <231>, respectively. The recommendation for ROI in early development is an internal specification of NMT 1.0% with the knowledge that this specification may be tightened as development progresses. The current USP heavy metals test is not typically sensitive to many of the metals used in an DS synthetic route and is also currently scheduled to be retired in the near future. As such, residual metals are often monitored internally by inductively coupled plasma–mass spectrometry (ICP–MS) or ICP–atomic emission spectroscopy (OES), or some other metal specific test. The recommended limits for these metals are those set forth in EMA guidance (14). This guidance provides classifications and permitted daily exposures (PDEs) for many of common metal catalysts and metal reagents. Limits for metals not contained within this guidance should be discussed with the internal product development team and appropriate drug safety organization.
Water content, polymorphic forms, and particle size. The proposed internal specifications for water, polymorphic form and particle size distribution (PSD) are all "report results" for compounds in early development. For water content, there is normally limited information available about a compound's sensitivity to moisture in early development. Although it is important that data be collected, initially the acceptance criteria should be "report results" unless the product quality is known to be sensitive to water. In the case where the DS is a known hydrate or shown to be hygroscopic, a target water content range is typically established in the DS specification.
X-ray diffraction, Raman, and solid-state NMR can be used to monitor the polymorphic form of the DS. Because the polymorphic form can impact on solubility, stability, and bioavailability, any change in form is typically monitored during stability studies.
Particle-size distribution (PSD) can be crucial to the ability to formulate the DS into the desired dosage form. In early development, many of the formulations are relatively simple (e.g., powder in a bottle) and the PSD information is normally gathered for development purposes only as an internal test. However in certain cases (e.g., low dose tablets, inhaled products), it is worth considering a suitable PSD target which is normally set in collaboration with the formulation development group.
Other tests to consider. Other tests may be considered as additional specification tests or non-specification tests for data collection purposes. For example, certain physicochemical properties of the DS, such as pH of an aqueous solution, melting point/range, and refractive index may be considered depending on the physical nature of the DS and its intended use. Similarly, there may be a need to specify the total count of aerobic microorganisms, the total count of yeasts and molds, and the absence of specific objectionable bacteria (e.g., Staphylococcus aureus, Escherichia coli, Salmonella, Pseudomonas aeruginosa) in the DS. If so, these should be suitably determined using pharmacopeial procedures.
Quality attributes that affect DP performance are typically not known during the early stages of drug development. Regulatory specifications should focus on ensuring that accurate and reproducible dosing can be achieved in the clinic and that patient safety is not compromised. For many tests, it is important that characterization data be acquired, reported, and monitored to gain an understanding of the DP in the context of characterizing chemical, processing, and packaging sensitivities. As product development continues, the DP formulation and process, along with the corresponding analytical methods usually undergo significant changes. The specifications evolve as additional knowledge is gained (e.g., tightening or widening acceptance criteria, adding tests).
As mentioned in the introduction to this paper, the authors have purposely limited the scope to oral dosage forms with an emphasis on US filings. The following sections outline proposed specifications for powder-in-bottle (PIB), powder-in-capsule (PIC), and tablets and capsules used in early development.
Powder-in-bottle and powder-in-capsule specifications. The PIB formulation is the simplest presentation of a DP for early clinical trials. It involves extemporaneous compounding of the DS into a solution or suspension for oral administration. The development of PIB requires a solubility assessment of the DS and selection of a pharmaceutically acceptable vehicle based on the expected clinical dose range. The DP is then manufactured by weighing the DS into appropriately sized bottles for reconstitution with the chosen vehicle at the clinical site. With the selection of PIB for clinical trials, the product development resources and timelines can be reduced significantly as there is no formal formulation development and thus additional analytical testing for stability, content uniformity, and dissolution are not necessary.
Because only neat DS is weighed into the bottles, the specifications for the release of the DS can be readily used to release the DP. Thus, the results of the appearance and identification tests used initially for releasing the DS can be used for the DP as well. Similarly, the initial impurity results for the DP are normally taken from the DS release data and the degradation products are monitored as part of the recommended DP stability assessment. For PIB assay, the 90.0–110.0% range covers the typical variability observed in fill weights for this formulation. A stability study of the reconstituted PIB is normally conducted to support its use at the clinical site within the recommended storage conditions, as well as holding and dosing times.
Verifying the uniformity of the dosage units is recommended as an internal specification test only. In PIB cases where it is intended to be weighed at the clinical site, a simple weight check during release testing assures that sufficient DS is contained in the bottle. This weight check may be omitted from the DP specifications if it is conducted as part of an in-process control. In cases where the entire contents of the PIB are to be used to make the clinical dosing solution and only a small amount of material (e.g., 1–2 mg) is provided in the bottle, then a more suitable quantitative analytical technique (e.g., a chromatographic method) may be required to verify the accuracy of the dosing concentration.
Similar to PIB, the PIC formulation is another simple presentation of neat DS in a capsule. PIC also provides dosing flexibility but has the added advantage of allowing easy manufacture of matching placebos. The only major difference in its development process compared with PIB is that a compatibility study of the DS with the capsule shell should be done to select a suitable capsule.
The typical PIC specification tests used in early development are comparable to those used for PIB formulations (see Table III). Specifically, appearance, identification, and assay all rely on the DS release results. Uniformity of PIC dosage units is performed according to USP General Chapter <905> but it can be omitted as a regulatory specification if it is part of an in-process control. In addition, disintegration test per USP General Chapter <701> is recommended to ensure that the capsules rupture to allow the release of the drug for absorption.
Tablet and capsule specifications. In early development, tablet and capsules for oral administration often employ "fit-for-purpose" formulation approaches designed to be suitable for wide classes of compounds, with the ultimate goal of facilitating rapid entry into FIH clinical trials. In the case of tablets and dry fill capsules (DFC), these formulations often employ a dry blend or granulations of a nonreactive diluent, a disintegrant, and a glidant to aid in processing. As shown in Table IV, standardized specifications are frequently established for capsules and tablets that are used in early development that can be segregated into the following attributes:
Description and identification: Visual description of the dosage form and correct identification of the active dose are critical to the integrity of the clinical study and thus are important attributes to be included in the DP specifications. The appearance specification should note the external color and shape of the dosage form. A single discerning identification test is normally sufficient and may be derived from the HPLC test used for assay or impurities based on the comparison of the sample retention time or photodiode array spectrum to that of a comparator DS batch.
Assay: An assay specification of 90.0–110.0% is normally attainable and controllable for most tablet and capsule formulations used in early development and ensures dosage integrity and patient safety. Additionally, this acceptance criteria provides reasonable formulation process control while accounting for typical assay variability and formulation inconsistencies in early development given the higher levels of impurities/degradation products normally observed at this stage.
Impurities and degradation products: Similar to the earlier proposal for DS, it is proposed that identification and qualification thresholds of three times those listed in ICH Q3B guideline (regardless of maximum daily dose), be applied for both impurities and degradation products in DP in the early stage. The proposed limit for unspecified individual degradation products in early development is NMT 1.0%. The limit of 5.0% for total degradation products in early phase DPs is higher than the corresponding limit of 3.0% for total impurities in DS due to the additional variability contributed by the formulation excipients, DP manufacturing process, and DP analytical methods.
In early development, these limits are justified because clinical studies are of limited size and duration and stability information on early drug candidates with respect to sensitivities to moisture, hydrolysis, and oxidation is still being acquired. Later in development, process control, formulation design, and product protection strategies to minimize product degradation can be implemented after the compound sensitivities are better understood and thus tighter degradation product controls are justified.
Uniformity of dosage units: The uniformity of active material in dosage units is important to the integrity of the clinical trial and to patient safety. The guidance for acceptance values is defined in USP General Chapter <905>. These acceptance criteria set a minimum standard for batch homogeneity and should be attainable at all stages of development for both capsules and tablets.
Water content: As described for DS, a DP specification only needs to be established to control moisture levels in an investigational capsule or tablet dosage if the product quality or performance is known to be sensitive to water. As development progresses and additional knowledge is attained about product performance and stability in the presence of water, a specification may be applied, as necessary for release, shelf life, or both.
Dissolution and disintegration: For rapidly dissolving immediate release formulations, it is recommended to include disintegration as a regulatory filed specification. Dissolution may be performed as an internal specification (i.e., report results without defined acceptance criteria) to gather product knowledge during early development (e.g., for poorly soluble drugs). As additional knowledge is gained toward establishing an in-vitro–in-vivo correlation (IVIVC), dissolution acceptance criteria should be established in later development (i.e., Phase 2b and beyond).
Other tests to consider. Other tests may be added to the DP specification as required. For example, residual solvents should be tested if solvents are used in the DP manufacturing process. Similar to DS, microbial testing may be considered, although a risk assessment may be performed to justify not including this test in the specification for solid oral dosage forms in early development.
Some in-process control tests such as hardness and/or friability may have a critical impact on drug product quality (e.g., chewable tablets). In these cases, acceptance criteria should be included in the specification.
A standard, risk-based approach has been presented for setting DS and DP specifications in early development for conventional solid oral dosage forms intended for US regulatory submissions. The recommendations herein are aimed at ensuring patient safety while allowing the flexibility to adapt to the frequent product and process changes that occur early in development. The authors' goal is to promote clarity and consensus within the pharmaceutical industry and to establish a more detailed approach to specifications in early development that are aligned across the industry and regulatory agencies. To further stimulate discussions on these approaches within the industry and with worldwide health authorities, this IQ working group is planning on conducting a workshop in the near future to promote robust debate and discussion on these proposed specifications in early development. In closing, it is recognized that each company needs to evaluate these early development recommendations based on the objectives of their individual drug development programs and may choose not to adopt this industry proposal on phase appropriate specifications.
Michael Coutant works in Analytical Research and Development at Pfizer Inc. (Groton, CT); Zhihong Ge works in Analytical Chemistry at Merck & Co. Inc. (Rahway, NJ); James S. McElvain* works in Analytical and QC at Kythera Biopharmaceuticals (Calabasas, CA); Scott A. Miller works in Analytical and Bioanalytical Development at Bristol-Myers Squibb Company (New Brunswick, NJ); Dennis O'Connor works in Quality & Records Management and Frank Swanek works in Analytical Development, both at Boehringer Ingelheim Pharmaceuticals Inc. (Ridgefield, CT); Michael Szulc works in Analytical Development at Biogen Idec (Cambridge, MA); Mark D. Trone works in Analytical Development–Small Molecule at Millennium Pharmaceuticals, Inc. (Cambridge, MA); Kirby Wong-Moon works in Analytical Research and Development at Amgen Inc. (Thousand Oaks, CA); Mehran Yazdanian works in Pharmaceutical Development at Teva Global Branded Products R&D (West Chester, PA); Peter Yehl works in Small Molecule Analytical Chemistry and Quality Control at Genentech (South San Francisco, CA); and Shuhong Zhang works in Process R&D, Global Pharmaceutical R&D at Abbott Laboratories (North Chicago, IL).
*To whom all correspondence should be addressed.
1. A. Eylath et al., Part I, Pharm. Technol. 36 (6) 54–58 (2012).
2. D. Chambers et al., Part II, Pharm. Technol. 36 (7) 76–84 (2012).
3. R. Creekmore et al., Part III, Pharm. Technol. 36 (8) 56–61 (2012).
4. B. Acken et al., Part IV, Pharm. Technol. 36 (9) 64–70 (2012).
5. P. Kurtulik, Pharm. Technol. 31 (4) 156–169 (2007).
6. ICH, Q6A Chemical Substances (ICH, Geneva, 1999).
7. L. Müller et al., Regul. Toxicol. Pharmacol. 44, 198–211 (2006).
8. ICH, S9 Nonclinical Eval. for Anticancer Pharm. (ICH, Geneva, 2009).
9. ICH Q3A(R2) Impurities in New Drug Substances (ICH, Geneva, 2006).
10. ICH Q3B(R2) Impurities in New Drug Products (ICH, Geneva, 2006).
11. ICH Q3C(R5) Impurities: Guideline for Residual Solvents (ICH, Geneva, 2011).
12. ICH, M7 Assess. and Control of DNA Reactive (Mutagenic) Impurities in Pharma. to Limit Poten. Carcin. Risk (Draft) (ICH, Geneva, 2012).
13. CHMP, Guideline on the Limits of Genotoxic Impurities (EMA, 2007).
14. CHMP, Guideline on the Spec. Limits for Resid.of Metal Catal. or Metal Reagents (EMA, 2008).
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SAN FRANCISCO – Several tornadoes touched down during storms in Northern California, including one twister near Sacramento that damaged a dozen homes and left a path of debris about 300 yards long.
The National Weather Service says a funnel cloud touched down near Roseville shortly after 6:15 p.m. Wednesday.
Fire Department Division Chief Kathy Finney tells the Merced Sun-Star (http://bit.ly/1dQfV8X) that 12 houses suffered roof damage and six reported fence damage. No injuries are reported.
The weather service says a tornado also touched down in Ordbend, in Glenn County. KNTV says there are reports of at least four twisters, which are rare for California.
The northern half of the state is experiencing wild weather including thunderstorms packing heavy winds.
Showers are likely to continue through the weekend.


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Texas Oil and Gas Industry Accident Injury Lawyers
Pipeline Explosions | Negligent Maintenance of Valves, Joints and Pipes| Product Liability Claims | Negligent Hiring, Training or Supervision| Failure to Address Gas Leaks
Texas is in the middle of an oil boom—new pipelines are under construction across the state, bringing crude oil from the ground to the refinery. In their haste to maximize production and profits, though, oil companies are taking too many shortcuts in the design, construction and maintenance of those pipelines. The result—pipeline explosions that cause serious injury or death to workers or others in proximity to the pipeline. If you or someone you love has been seriously injured in a pipeline explosion, our attorneys can protect your rights.
At Bailey & Galyen, we have more than a quarter of a century of legal experience to people who have been hurt in an accident in the oil and gas industry. We fight for the rights of people throughout Texas, taking the time to learn the details of your accident, as well as your goals, so that we can help you make the best decision about how you want to proceed. We will conduct an exhaustive investigation of the facts and circumstances of your case, and will go to the site of your accident, if necessary. We work with a highly skilled team of experts, including engineers, geologists, medical professionals and financial planners, building the strongest case for your full financial recovery.
We provide a free initial consultation. Contact our office online or call us at one of the numbers listed below to schedule an appointment.
Texas Pipeline Injury Lawyers
We handle all matters related to claims for injuries suffered in a pipeline explosion. Our attorneys will gather and assess all evidence, prepare and file all necessary documentation, and be your voice in all hearings or proceedings. We will help you seek damages for all your losses, such as wages and income, medical expenses, loss of companionship or consortium, and physical pain and suffering. We take all types of injuries claims, from sprains, strains and other soft-tissue injury to serious and catastrophic loss, including broken bones, brain or spinal cord injury, burns, permanent scarring or disfigurement, paralysis, amputation or loss of limb, or wrongful death.
We take pipeline accidents resulting from any type of carelessness or negligence, such as:
- Human error, including carelessness in hiring, training or supervising workers
- Negligent maintenance, including defective repair welds, negligently installed valves, joints or service lines
- Failure to replace or repair a pipeline in a timely manner after reports of suspected gas leaks or other concerns
- Failure to follow appropriate safety regulations or codes
- The breakdown of or exposure to dangerous or defective parts, products or equipment
- Pipeline breakdown— metal fatigue, corrosion or exposure to caustic chemicals
Contact Bailey & Galyen
Contact our office by e-mail or call us at one of the numbers below to schedule a free initial consultation with an experienced Texas pipeline explosion injury lawyer. Our phones are answered 24 hours a day, seven days a week.
Personal injury lawsuits are complicated and expensive to mount and that is why we take all cases on contingency, meaning there is never a fee until we recover a settlement in your favor.
Locations Throughout Texas
We provide skilled legal representation to individuals across the State of Texas including the Dallas-Fort Worth communities of Arlington, Bedford, Dallas, Fort Worth, Irving, Grand Prairie, Mesquite and other cities in Texas including Houston Clear Lake / NASA, Texas.


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Pack of 2 Turn Button Bases (2 Hole)
Pack of 2 Turn Button Bases (2 Hole)
Pack of 2 Turn Button Bases (2 Hole)
Refund Policy:
Thanks for purchasing our products at quaycanvas.net operated by Quay Canvas Ltd.
In order to be eligible for a refund, you have to return the product within 14 calendar days of your purchase.
The product must be in the same condition that you received it and undamaged in any way. Customers are also expected to cover postage costs for the return.
After we receive your item, our team of professionals will inspect it and process your refund. The money will be refunded to the original payment method used during the purchase.
For credit card payments it may take 5-10 business days for the refund to show on your credit card statement.
If the product is damaged in anyway, or you have intiated the return after 14 calendar days have passed, you will not be eligible for a refund.
Exchanges of sizes and colours of products are also available, and a return should be made in the same way for exchange products to be issued.
If anything is unclear or you have more questions, feel free to contact our customer support team.


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Digital Design Original Single Art Piece Grades 3-5
Entry #:
Entry Title:
The Snow Fox
Project Description:
Click the button for the full size photo or complete project.
Projects must be designed digitally. Entrants are encouraged to be creative and incorporate clip art, photos, and interesting fonts in the appropriate projects. However, if copyrighted elements are used, be sure they are considered Fair Use or provide written permission in your documentation. Any copyrighted or Creative Commons materials should also be credited on your entry form.
Entries should be submitted using either a PDF or image format. See your Media Specialist for assistance.
Judging Criteria
Content Achieves Purpose
The purpose of your production should be apparent to your audience. Some thread of unity carried out in the production should be easily determined by your plan and purpose.
Content Suitable to Audience
The choice of subject matter should be
appropriate for the audience indicated. It should take into account aspects of the audience
including age, gender, knowledge on a subject, etc. Will the specified audience care about the
content of the production? Would the story or message be clear to the audience?
An entry should be a statement of your own ideas that you wish to communicate to your audience. If you develop your idea in an interesting or unusual manner, your production will have Creativity. Judges will be looking for the freshness or novelty of an idea or method. The ability to think or express oneself in an independent and individual manner should be apparent.
Judges will be looking at the overall design of your production including font size, font type, and the arrangement of words and graphics.
Overall Effectiveness/Presentation
The production should make a strong impression. Judges will rate the general effectiveness of your product by how well it clearly expresses your ideas.
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Judges will look for the way in which a particular technology has been utilized to its fullest potential in the development of the project.
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Home > ASME Articles > Recessionary Woes and Alcoholic Problems
Although the U.S. recession officially ended in June 2009, many Americans still struggle to make ends meet. A recent study has examined the relationship between different types of economic loss experienced during the recession – job loss, reduced work hours/pay, difficulty paying for housing, housing loss, and loss of retirement savings – and alcohol consumption and problems, finding that men and middle-aged Americans are at higher risk for multiple, adverse alcohol outcomes.
Results will be published in the April 2014 online-only issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.
"Research suggests that economic downturns can have severe impacts on stress and mental health," said Nina Mulia, a scientist with the Alcohol Research Group of the Public Health Institute and lead author of the study. "A 2009 study of 26 European Union countries found that a mass rise in unemployment such as three percent led to significantly higher suicide rates among people under age 65. Additionally, a 2011 longitudinal study using U.S. data showed that increased unemployment was linked to declining psychological health. Furthermore, a recent review of many individual-level studies concluded that job loss is associated with a greater risk for depression and anxiety symptoms."
"This study brings us a long way towards confirming how much economic shocks impact peoples' health," added Laura A. Schmidt, a professor of health policy at UCSF School of Medicine. "It emphasizes the role of economic stress – what it's like to lose a job, a house, a retirement 'nest egg'—and how much that impacts a person's state of mind and leads to problems with drinking. The authors note that the price of alcohol has gone down a lot in recent years. Maybe this made it easier for people stressed out by the recession – and the personal toll it took on their own families and themselves – to overcome the inhibition to buy alcohol. It's understandable when a person is in such a terrible place, fearing for his economic future, and feeling responsible for his family."
"Our study is an individual-level study focusing on economic loss experienced during a severe recession and how this relates to drinking patterns and problems," explained Mulia. "Unlike many prior studies focused on unemployment and alcohol consumption, we assessed different types of economic loss that were common during this last recession, and a variety of distinct alcohol outcomes."
Mulia and her colleagues drew on data from the 2009-10 U.S. National Alcohol Survey for 5,382 individuals (3,445 females, 1,937 males). They estimated associations between economic loss measures and total alcohol consumed in the previous year, frequency of drunkenness (a key predictor of alcohol-related problems), negative drinking consequences, and alcohol dependence in the overall sample as well as within gender and age groups (18-29, 30-49, 50+), while controlling for demographic characteristics and alcohol history.
"In the overall sample, people who experienced severe economic loss, such as job or housing loss, were at greater risk for monthly drunkenness and alcohol-related problems, even after taking into account an individual's history of alcohol problems prior to the recession," said Mulia. "Those who experienced only moderate economic loss appeared to have drinking outcomes similar to those who were unaffected by the recession. Our subgroup analyses suggest that the effects of severe economic loss on drunkenness and alcohol problems were mostly concentrated among men and the middle-aged. They also showed that relatively moderate though common losses, such as a reduction in work hours/pay and the loss of retirement savings, were actually associated with increased drinking in some subgroups – specifically, women and older adults – though not drunkenness."
"For a long time, alcohol researchers took it as a truism that people with lower incomes are less likely to buy alcohol, and therefore less likely to have alcohol problems," added Schmidt. "This study kind of turns that assumption on its head. In a period of national economic distress, where more than half the population reports being personally affected by an economic downturn, people suffering the most severe forms of economic loss are likely to turn to alcohol for a stress-reliever. Unfortunately, some of the most severe manifestations of stress involve alcohol-related harms that could involve others—like drinking and driving and family violence. This is where we all need to, as a society, think about how we can do a better job at buffering vulnerable people from the harms that come with major economic downturns. This is important particularly because kids are affected by these harms."
Mulia and Schmidt noted that men and middle-aged Americans might be more affected by the experience of severe economic loss due to several reasons: gender norms around drinking, childrearing and family responsibilities that may constrain heavy drinking among women, and the fact that men are still, in many families, the primary breadwinners; furthermore, the middle-aged are likely responsible for the economic wellbeing of others, both young children and possibly aging parents.
"Clinicians are already doing a lot to promote screening and brief intervention on alcohol problems," said Schmidt. "This study points clinicians towards specific target populations to worry about during future economic downturns – [men and] the middle-aged. These 'vulnerable populations' are those who, when faced with particular challenges, are the most likely to resort to health behaviors that harm themselves and others."
Mulia agreed, pointing out "when people lose jobs or housing, or have their hours/salaries cut, visiting the doctor might not be a priority, especially if they have lost their health insurance. So we need ways to reach the people who have been most impacted by economic loss and link them with alcohol screening and brief interventions, as well as other health education and prevention efforts," she said. "This might mean that health programs should partner with unemployment offices, housing and social services, etc."
Mulia also pointed to the health benefits of a strong public safety net. "In addition to alcohol intervention, it is important to consider more broadly what might protect health and social welfare during macroeconomic crises," she said. "Research suggests that the adverse impacts of a recession on population health depend, in part, on social safety-net programs available in a given country. Initiatives and programs to foster job retention and housing retention, to help people to become re-employed, food programs – all of these might be important in reducing the adverse health impacts of a recession."


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If you have been working in front of your computer for long hours then this exercise video is for you. The simple exercise routine is actually intended for office workers, but mommies like you and me can also do this at home while we are at rest from our daily chores. For bloggers, you can allot a minute or two to do this exercise so you'll improve your energy level before you get really busy with your online activity. Health experts say it's best to start your day with an exercise.
I got this video from one of the health conferences I attended years ago. I have not watched the entirety of this video, but now that I post it here it will be convenient for me to play this video anytime I want while in front of my computer. You can exercise whichever way you want. You can do it sitting down or standing like the man and lady demonstrators in the video.
"Time for Health" A Healthy WPRO Activity is developed by the College of Human Kinetics (CHK), University of the Philippines Diliman (UPD), Quezon City Philippines for the 51st Session of the World Health Organization, Regional Committee for the Western Pacific, Sept. 2000.


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Although I'm very much enjoying the one of the games I'm in, the other players seem to be flagging and losing interest. This is a bit disheartening as their lack of enthusiasm is bringing down the game for me and I'd like to help get them re-motivated and back into it The GM is doing all the right sort of things (see associated posts) but...
But how can I as a player motivate my fellow players to regain their enthusasm for the game?
They certainly enjoy things once they "get going" and get themselves into it, but their enthusiasm at the start and here and there is lacking and they tend to wander subjects. This is a primarily social game (WoD); Combat is pretty rare (once in every four sessions or so) and none of the characters are really statted for it (except mine, bizarrely). The other players will engage with NPCs. They do take a long time to wind up to play (first hour or so) but they'll wander in play once it's started as well. We do have problems with occasional pauses (online game) and getting back rolling again after, but it's as much distracting irrelevant talk that seems (to me) to indicate wandering interest.
Related to this question:
How to motivate players without the promise of gold and XP? and
How do I help my players get more engaged in the story?


text: The approach to retirement is a balancing act between growing and protecting assets. In general, the closer we get to taking retirement income, the more the balance tends to shift toward protecting years of hard-earned dollars. That balance may be more relevant now than ever. Call us if you'd like to discuss what options you have where your principal is protected and your risk is lower. We're always here to help.


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What is Forest Therapy?
Forest Therapy, also known as shinrin-yoku or "forest bathing," is the art and practice of using a combination of the human senses to become fully and mindfully immersed in a natural setting, primarily a forest, so that participants are under a canopy of trees. However, any natural environment will do.
The practice began in Japan, who studied its healing effects in great detail in hopes of addressing the growing health concerns attributed to the stresses of Japanese work culture. It did not take long for western scientists to begin to take note of these studies and perform their own. Such studies have demonstrated a wide array of health benefits, especially in the cardiovascular and immune systems, and for stabilizing and improving mood and cognition.
This rather intense, yet relaxed practice renews us in a way that allows our inner peace and health to radiate beyond the Forest Therapy walk and positively impact our day to day experiences.
Below are some frequently asked questions…
There are no formal definitions for terms like Forest Therapy, Forest Bathing, Nature Therapy and Shinrin-Yoku but this our approach to these terms.
Forest Bathing is the English translation of the Japanese word and concept Shinrin-Yoku and what has inspired this movement. It is the simple art of spending quality time outdoors, ideally under the canopy of trees.
Forest and Nature therapy both refer to a more structured or facilitated application of forest bathing that adds elements of nature teachings and mindfulness exercises. It is especially useful since the idea of spending "quality time outdoors" has become so foreign and difficult for us. How often do you see people in parks and hiking trails glued to their phones or carrying radios? Silence, stillness, and mindfulness are so far removed from our fast paced life that it helps to have someone there to guide and encourage you, and help maintain that space so that the benefits associated with forest bathing can be more readily reaped.
Forest Therapy attracts a wide range of demographics from students to stay-at-home parents to CEOs to retirees so there is no one type of person suited for forest therapy. Some guides cater to specific groups and/or take a more "New Age" type approach complete with crystals and other typical accoutrements.
We take a rather practical and simple approach, trying to avoid metaphysical jargon while still drawing on a wide range of techniques and exercises which may sometimes come across as a little "New Age." We pull from many cultures and self-care practices to ensure there is something for everyone and to keep things varied and interesting.
As always, all invitations are optional and done in a judgement-free zone. We invite you to try new things when comfortable and decide for yourself what is useful for you. It is about the experiencing, not the doing.
There's a growing body of evidence that the practice can help boost immunity and mood and help reduce stress. The science aside, the simple act of taking a break from the stresses of modern life and the technology designed to bombard our senses and demand our attention has a positive effect on our well being.
Given the testimonials which abound from various sources that show the value of forest therapy, and the affordability and simplicity of it, we invite you to try it for yourself. As with any form of self-care, what you bring to it plays a large role in what you get out of it, so come with an open, playful, and curious mind.
While your guide will try to keep the experience varied each time, unless a specific walk includes a hike (which would be made known at registration) it is safe to expect a leisurely walk on an easy, well-maintained trail. The distance will not usually be very far (around 3/4 of a mile) and most of the walks will be under forest canopy when possible.
During the walk guests will be invited to participate in series of guided meditations and mindfulness exercises to help become more present, awaken the senses, and reconnect with Nature. At the end of each walk is a tea ceremony with some snacks.
Sessions vary from one to three hours in duration depending on location, weather, and size of the group.
Traditionally no, the walks are not intended to be strenuous and are on easy trails. Over a period of two to three hours we do not actually cover more than a mile, probably closer to a half mile. It is not about distance or getting a workout, but about the experience. Time will likely go faster than you would expect or want!
That said, we have developed a program which merges with hiking since there are therapeutic advantages to physical exercise, and the moments after strenuous activity can be conducive to mindfulness work. (Not to mention the joy of the scenic spots along the way.) We will clearly indicate when there would be hiking involved.
So let's just say there are options for those interested! We want to have fun with this!
We encourage you to get outside every day.
As far as forest bathing or forest therapy goes, its effects are cumulative and so developing a weekly or semiweekly practice will go a long way. These do not always have to be with a guide although you'll learn many techniques and exercises from one and it is easier to stay immersed and present when a guide is assisting. (We do offer discount packages for those wanting a more regular facilitated experience.)
We welcome adults of all ages and retirees frequent our walks. Walks are not strenuous unless that specific event is listed as being paired with a hike.
Ultimately we need to rely on your judgement on what level of activity you are comfortable with and events can be catered to your needs within reason. If you feel you have special needs then private sessions allow us to better accommodate you without worry of disrupting the group.
We invite you to reach out to us and discuss your needs. Adult day care and nursing homes are also welcome to reach out to us for ways in which we can help bring the forest therapy experience to your facility!
Challenge accepted!
We want everyone to experience Forest Therapy. Private sessions are easier to plan for special needs, but if we have advanced notice of interest in attending a public group event we can search for places that can accomodate us.
Let's talk and see what ideas we can come up with! We may not be experienced with all situations so please be patient with us as we work out the details with you.
(We welcome service animals and ask that you check with the specified walk location to ensure the location will fit your needs.)
Here is a handy checklist of items I to bring on our walks:
- Dress comfortably. Loose fitting close and a layer or two if cold so you can add/remove layers based on your level of activity.
- Appropriate footwear (see below considerations)
- Weather gear as needed: umbrellas, rain ponchos or jacket/pants.
- Sunscreen and bug repellent.
- Water (ideally in a reusable bottle to lessen plastic use.)
- If the day is cold might want to consider bringing a thermos with a hot drink.
- Snacks or a light lunch for the end of the walk.
- Towel or blanket for sitting (if you need a portable chair you are welcome to bring it).
- If you need to take any medications with you consider this a reminder.
- Additional considerations:
Please consider using a reusable water bottle or thermos for your water so as to reduce waste. This is a great opportunity to become mindful of your personal impact on the environment. These little things do make a difference.
Bring a small bag for your garbage - we follow a carry in, carry out policy. We encourage participants to carry out at least one item more than they brought in should they stumble upon a stray discarded bottle or wrapper.
A note on footwear:
For a typical walk, there is no need to worry about heavy duty boots or hiking shoes since we do not walk very far unless that specific event was being paired with a hike. Barefoot is fine in most cases, but if you are not used to being barefoot outdoors it can be a bit intense on a trail so perhaps wear flip flops or sandals you are comfortable in which you can slip in and out of as needed. Ultimately wear what is comfortable.
Also check out our blog post on what to bring for more ideas.
It happens. If you need to leave early please let the guide know so it can be planned in a way to least disrupt other attendees.
There are many options available but a typical walk starts at $25 a person with group discounts and private walks available. While we try to use locations that are free to the public, some locations may charge a small entry fee which is not included in our fee.
We do offer the occasional free (with optional donation) event to allow those with concerns about cost or value to still enjoy their moment of self-care. These walks are exactly the same as the paid ones.
(Discounted rates for low income individuals and group rates for organizations are available.)
I limit walks to a maximum of 10-15 people but prefer 5 or less. Private sessions are available for individuals, couples, and groups (friends, teammates, staff, etc.).
Primary focus is the Garrison/Cold Spring area, but there are walks offered in all boroughs of NYC as well as in Westchester and locations further north. The objective is to explore many places to find which locations work best for the group. Ultimately we'll concentrate on the areas that work best for our clients.
Both pets and children add an element of distraction or triggers to others so are generally not permitted on group walks. We'll make exceptions for well-behaved pre-teens if accompanied by a guardian.
However, if members are interested in organizing a pet and/or child friendly event, that can be arranged if there is enough interest or via a private session! (We're not too experienced with working with children but we love to learn and are willing to try out some ideas!)
We welcome service animals and ask that you check with the specified walk location to ensure the location will fit your needs.
Yes. I know it is not always easy to pull away from our phones and tablets, but this is an integral component of forest therapy. If you need to have your phone on at all times please book a private session so as to respect the experience of others in the group who welcome the momentary respite from our demanding technology.
If you have a watch you are encouraged to remove it as well for added peace of mind.
Not during the walk itself. We invite you to become fully present in your experience. Taking photos to capture a moment results in losing touch with the present. Social media can wait and is not welcome in this space. At the closing of the walk guests are welcome to take group photos, etc. but please ensure you have the permission of others who would be in the photos.
(At free events the guide may request to take some photos for use on the website/blog but this is an infrequent special exception.)
So as not to disturb the other participants we ask you to allow yourself this time to become more present and centered. There will be plenty time to chat during breaks and after the event.
This is your time. You will be invited to participate and that participation is completely optional.
If you are shy or have social anxiety consider a private session or just speak with a guide so he or she knows to respect your space. While any invitations from the guide will be simple and non-intrusive, please let us know when something makes you uncomfortable so we can better accommodate you.
You can absolutely do your own forest bathing. In fact you are encouraged to take away and use anything you learn from your walks with a guide on your own. The trick to getting the benefits of forest bathing is to 1) get into the woods and 2) slow down, quiet down, become present. It's that second part that can be difficult and why many like to supplement their personal practice with the help of a guide.
A guide's role is to help keep you engaged and provide various tools through which to help maintain presence and mindfulness. It can certainly enhance one's experience but everyone is encouraged to also do forest bathing on their own.
Apart from when the weather is deemed a safety concern our sessions will still take place.
Rain, light snow, and overcast days can really enhances one's sensory experience and thus benefit your session.
Be sure to check the weather and bring appropriate gear. Umbrellas are fine, rain ponchos are very useful and easy to pack.
No. Forest Therapy is not a substitution for professional help for those that need it - be it medical or psychological.
"Therapy" here refers to the therapeutic and healing attributed to the immersion in nature. Nature is the inferred therapist/healer. The guide simply provides structure and invites guests to participate in various exercises and practices to get the most out of the experience.
The event is smoke free. If you are not able to wait until the end to have a cigarette or e-cigarette you can quietly excuse yourself from the group to smoke at a reasonable distance from the others. Please be mindful of how smoke can travel and that these breaks remove you from the experience.
Drugs and alcohol have no place here and would impede your experience. You will be respectfully asked to leave if you are found to be under the influence.
Pretty much! The outdoors has its inherent risks (insects, wildlife, poisonous plants, and tripping hazards). We do our best to choose trails which are well maintained and generally the risks of insects and wildlife are low in this area. Still, if you are not familiar with the environment a certain level of caution is to be maintained. Never touch or eat plants you do not recognize, avoid disturbing insects and wildlife, and be mindful of your surroundings.
Traditional Forest Therapy walks are not strenuous but we sometimes include hiking so in those cases (which would be clearly indicated with the event's information) be sure to discuss any health concerns with the guide to ensure the level of intensity is within your limits.
Yes. We live in litigious times and even a leisurely stroll through the woods has its inherent risks. All participants sign a simple liability waiver at the start of the event to allow us peace of mind in offering our walks to the public.


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As a part of self study, I am trying to prove the following statement:
Suppose $X$ and $Y$ are topological spaces and $f: X \rightarrow Y$ is a map. Then $f$ is continuous if and only if $f(\overline{A})\subseteq \overline{f(A)}$, where $\overline{A}$ denotes the closure of an arbitrary set $A$.
Assuming $f$ is continuous, the result is almost immediate. Perhaps I am missing something obvious, but I have not been able to make progress on the other direction. Could anyone give me a hint which might illuminate the problem for me?


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Windows 8 Consumer Preview Event Scheduled For Feb 29
by Saumitra Bhagwat on February 9, 2012 8:41 AM EST- Posted in
- Microsoft
- Operating Systems
- Windows 8
Windows aficionado Paul Thurrott has just confirmed that the Windows 8 Consumer Preview event will be held in Barcelona, Spain on February 29, 2012. Coming from Mr. Thurrott, we would be inclined to believe that this is not a rumor.
There have been a lot of leaked screenshots of the supposed Consumer Preview build 8220 (or build 8225 if the @BuildWindows8 Twitter feed is to be believed) floating around the interweb these past few days. Some of the more aggressive changes include the disappearance of the iconic Windows Orb, or the Start Button as some of us still lovingly like to call it. Others are more subtle like changes to the Metro-styled start screen and a new translucent UI for Charm bar.
I quite like the Consumer Preview moniker being used this time around. The consumer-centric branding, just like the Building Windows 8 blog, demonstrates Microsoft's commitment to actively communicate progress on the OS and gather feedback from end users and developers.
The Consumer Preview should ideally be a feature-complete release, with future builds focusing on performance, stability and usability enhancements, rather than any major new features.
In any case, the wait shouldn't be too long now.
Source: Supersite for Windows
12 Comments
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faizoff - Thursday, February 9, 2012 - link
I just reinstalled the developer's preview on my spare SSD last night and didn't realize it took over the boot loader from my main Windows 7 installation.
Probably should've just waited for the consumer version to be released. -
dagamer34 - Thursday, February 9, 2012 - link
Yep, gotta be careful. Need to find a way to install the consumer preview on a USB drive without nuking the boot loader on Windows 7 install. -
Kelemvor - Thursday, February 9, 2012 - link
That'd be cool. I really want to try Win8 but don't want to have it mess up my Win7 machine. Maybe find a spare hard drive to install it on but that'd be a pain to keep swapping hard drives. Launching it from USB would be cool. -
B3an - Thursday, February 9, 2012 - link
Win 8 has the "Windows To Go" feature where you can install and run the whole OS from a USB flash drive. Just plug the drive in to any PC and away you go. Not sure if this is just for the Enterprise / Server version though. But maybe it will be in the Consumer Preview with an easy way to set it up from the new installer menu. Either way, it's a very cool feature and i hope it's in all versions. -
Andrew.a.cunningham - Thursday, February 9, 2012 - link
The Windows 7 beta was the Ultimate version, and in Win7 the Ultimate/Enterprise editions are identical except for branding and licensing. If it's an available feature, the Consumer Preview should have it. -
retrospooty - Thursday, February 9, 2012 - link
" Need to find a way to install the consumer preview on a USB drive without nuking the boot loader on Windows 7 install."
Unplug your hard drive, then do the install. Then plug back in, and choose your boot device manually. -
Mr Perfect - Thursday, February 9, 2012 - link
Yep, had to do just that with the 7 Beta. Otherwise 7 nuked the XP loader. This was one of the things I was hoping they'd improve on this time around. It really shouldn't be messing with other OSes on the PC. -
faizoff - Thursday, February 9, 2012 - link
When I installed win 8 dev preview I should've plugged the hard drive out. Last time I installed win 7 beta I did that. I was too lazy to do it this time and looks like my boot loader is taken over by win 8.
Going to play around and figure out what to do about it.
Also my Dev preview will not for the life of me shut down. I have to power it down with the power button.
So annoying. -
krazyderek - Thursday, February 9, 2012 - link
do the new windows releases not run well in virtual machines likes virtual box, parrallels, vmware etc?? -
arnold58 - Friday, February 10, 2012 - link
BCD should sort out your problems .. at least it did on my win7/winXp/W8. was going to add ubuntu, too much methinks


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If, we as a community, are intending to accelerate the development of interstellar travel we have to glower at the record and ask ourselves some tough questions. First, what is the current record of the primary players? Second, why is everyone afraid to try something outside the status quo theories?
At the present time the primary players are associated with the DARPA funded 100-Year Starship Study, as Icarus Interstellar who is cross linked with The Tau Zero Foundation and Centauri Dreams is a team member of the 100YSS. I was surprised to find Jean-Luc Cambier on Tau Zero.
Gary Church recently put the final nail in the Icarus Interstellar's dreams to build a rocket ship for interstellar travel. In his post on Lifeboat, Cosmic Ray Gorilla Gary Church says "it is likely such a shield will massive over a thousand tons". Was he suggesting that the new cost of an interstellar rocket ship is not 3.4x World GDP but 34x or 340x World GDP? Oops!
Let us look at the record. Richard Obousy of Icarus Interstellar and Eric Davis of Institute for Advanced Studies claimed that it was possible, using string theories to travel at not just c, the velocity of light but at 1E32c, or c multiplied by a 1 followed by 32 zeros. However, Lorentz-FitzGerald transformations show that anything with mass cannot travel faster than the velocity of light. Note that Lorentz-FitzGerald is an empirical observation which was incorporated into Einstein's Special Theory of Relativity.
It is quite clear that you can use string theories to say anything you want. I used the term 'mathematical conjecture'.
In April 2008 the esteemed Michio Kaku said in his Space Show interview, that it would take several hundred years to do gravity modification. But Michio Kaku is a string theorist himself. And I might add down to Earth one at that, since his opinion contradicts Richard Obousy and Eric Davis.
Then there is George Hathaway also with the Tau Zero Foundation who could not reproduce Podkletnov's experiments, even when he was in communication with Podkletnov.
And this is the one group our astronaut Mae Jemison, leader of the 100YSS effort, has teamed up with? My sincerest condolences to you Mae Jemison. Sincerest condolences.
For the answer to the second question, you have to look within yourselves.
Benjamin T Solomon is the author & principal investigator of the 12-year study into the theoretical & technological feasibility of gravitation modification, titled An Introduction to Gravity Modification, to achieve interstellar travel in our lifetimes. For more information visit iSETI LLC, Interstellar Space Exploration Technology Initiative.
Solomon is inviting all serious participants to his LinkedIn Group Interstellar Travel & Gravity Modification.


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Dude, Hugh made me soooo sad.>> I loved him.;-; D< AND THEY PURPOSEFULLY DO THAT. Make the most adorable, lovable character, with everything to live for, and then kill'em off.;-; "Why're they putting daddy in the ground? Daddy has to go to work. Daddy..." ;-;;;;;;;;;;;
I've cried reading Naruto... >> [is narutarded]*spoiler*the idea for a spoiler is to make it too small to read at a glance, this was not, and yes it spoiled it for me thanks please make it smaller
Hm, when I was younger ANY of the Pokemon movies would make me cry. Now I have the experience to know that whoever dies really isn't dead.
Toradora. Oh my god. I bawled my eyes out at episode 19 : [ I adore Taiga so much~~!!
most recent one is Code Geass when i finished iti was bawling
I cry easily so my list would probably be long ._____.;;; I'll shorten it to bawling XDAIR. Of course. You can't NOT cry. When she was running towards him and "Goal" TT-TT WaaauuuhhhhChrno Crusade. The anime ending made me CRY, and manga ending made me BAWL. This is embarrasing. Full Moon volume 4 XD When Takuto tells Mitsuki he loves her, and she starts yelling at him D: Well, actually, in general, Arina Tanemura manga make me cry. When Zen died in KKJ, I cried. And I cried like every volume in Shinshi Doumei Cross.ION and Kyoko are the only exeptions really. Her art just portrays the emotion so well ;___;Erementar Gerad. The last episode was so sad, but it got happy I'm still waiting to see how the manga ends Rurouni Kenshin. Quite obvious WHY.Ones that didn't kill me but made me sniffle: Hibiki's Magic, Sand Chronicles (It can only get sadder), FMA, Millenium Snow*CRYBABY* God XD
god, when i finished code geass you would've thought that my whole family had died.
Quote from: Hidamari on May 16, 2009, 06:12:51 pmgod, when i finished code geass you would've thought that my whole family had died.x3Sahara cried and I just sat their.I never really got to enjoy the anime because I was so upset that they killed off the two best characters..Euphie and Mao. x3
I know everyone has one. I just started watching Tsubasa Chronicle and I know I will end up crying at least once before the series is over. Have you ever cried while watching anime? or had an anime that really got to you in some way?


text: When Hajj Abdul Karim Ha'eri Yazdi entered Arak he established a School of Theology, which quickly caught up with Isfahan's Theology School and which at the time was the best in the country. Therefore, Rouhullah decided to join this newly established Theology School and so went to Arak, which is 60 kilometers away from Khomein. There, Imam Khomeini studied for one year under the great scholars Sheikh Mohammad Ali Borojerdi and Agha Sheikh Golpayegani. During this time he also studied the book Sharhe Lame' by Agha Abbas Araki.


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14CT Stamped Ecological Cotton Cross Stitch Kits DIY Lighthouse Embroidery Needlework Mosaic Craft Artwork for Home Decor Gift
1. A guide graphic composed of different numbers and symbols tells you where to draw the Cross stitch and which color thread should be used. All you have to do is follow the symbols on the paper. Learn how to get started.
2. Soft Natural ecological cotton, colorful and durable, making your Cross Stitch silky, vivid and long lasting.
3. The cross-stitched artwork will bring you a pleasant time and a sense of accomplishment when finish the work. Your cross-stitch artwork can be used as a home decoration, or as a unique, meaningful and irreplaceable gift for your loved one.
Canvas Size:
F782: 30 X 40cm/11.81 X 15.75\"
White Border Size: 4cm/1.57\"
Material: Cotton
Fabric: Stamped
Cross Stitch Cloth: 14CT 2 Strands
1. NOT Including Frame.
2. The color block in the drawing does not represent the color of the embroidery thread. Please carefully identify the symbol or the serial number corresponding to the color block, and select the thread number according to the serial number requirements.
3. Due to the different monitor and light effect, the actual color of the item might be slightly different from the color showed on the pictures. Thank you!
4. Please allow 1-3mm measuring deviation due to manual measurement.
Package Content:
1 X Embroidered Cloth
2 X Embroidery Needle
1 X Embroidery Thread Set
1 X Manual
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Hunt or Be Hunted: Get the Design Job You Want
"Matchmaker, matchmaker, make me a match, find me a find, catch me a catch…",lyrics from Fiddler on the Roof about finding a perfect partner. Wouldn't it be great if you could have someone to guide you towards what is a match for you, advise you in your career life, help you weed through the losers to find the fabulous 'one' that will make you whistle on your way to work AND whistle on the way home?
In Hunt or Be Hunted - How to get the Design Job you Really Want, you will be privy to the insights and success stories of three of the industry's most respected representatives in their knowledge domains. You will also hear from a leading expert in the placement of designers. Each will relate real-world experience, guiding audience members through the maze of questions a designer has in this frenetic job market.
Who are you as a designer? What do you want to do, and how do you know it's the right thing.
What's your story? How to present yourself, your portfolio, and where you want to be.
Where should you be full time or freelance? What that means to your life, your career and how you are viewed.
When is it right? To look, to change, to know if this is the one.
How do you get there? Choosing the right company, assessing/selling to what they need, closing the deal.
Don't be left in the dark. Don't make blind decisions. Be informed, be guided, then be sure. Listen to these respected resources to help yourself to, "…find me the perfect match."
Gina Bianchini
Gina Bianchini is passionate about how people use social software to organize and experience their interests and passions online and in the real world.
Bianchini was an early pioneer in social software, beginning work in this area in 2004 when she and Marc Andreessen co-founded Ning (www.ning.com), the first and largest social platform for interests and passions online. She served as CEO of Ning from its inception to March of 2010, at which time Ning had 90 million monthly unique visitors, 46 million registered users, and 300,000 monthly active social networks across entertainment, politics, education, and interests. In December 2011, Ning merged with Glam Media, a premier brand advertising company.
Today Bianchini is the CEO and founder of Mightybell (www.mightybell.com), a new social platform seeking to revolutionize how online groups form, organize, and grow around interests, passions and goals in 2012 and beyond. The company is coming out of its beta this spring.
Gina has been featured on Fortune Magazine's "40 under 40," Huffington Post's 10 technology "Ultimate Game Changers," and 7x7 magazine's "Hot 20" list. Gina and Ning have been featured in Fast Company, Wired, The New York Times, Fortune, Forbes, and The Wall Street Journal. She has also appeared on Charlie Rose, CNBC, and CNN.
Prior to founding Ning, Gina was Co-Founder and President of Harmonic Communications, an early advertising tracking, measurement, and optimization software company backed by Sequoia Capital and acquired by Dentsu. She started her career at Goldman Sachs & Co.
Bianchini serves on the board of directors of Scripps Networks Interactive (NYSE: SNI), which owns HGTV, The Food Network, The Travel Channel, The Cooking Channel, The DIY Network, and Great American Country.
She graduated with honors from Stanford University and received her M.B.A from Stanford Business School. She is an advisor to The Clayman Institute for Gender Research at Stanford University; and She Writes, the largest social network for women writers globally.
Jason is Votizen's founding product designer and leads on product vision, visual design, and brand voice. Jason was the first designer hired at Mint.com in 2007 and held the leading role until Mint's acquisition, when he became a Designer-in-Residence for Bessemer Venture Partners. He's an advisor and mentor for 500 Startups, SV Angel, SSE Labs, and to many startups in Silicon Valley. In January 2012 he was named to Forbes 30 Under 30 for social media and mobile. He holds a Computer Science degree from the University of Pittsburgh, and was the youngest ever MFA candidate at Parsons School of Design.


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The FINANCIAL — By early last year, Apple's cash balance had built to a point beyond what we needed to run our business and maintain flexibility to take advantage of strategic opportunities, so we announced a plan to return $45 billion to shareholders over three years. As of next week we will have executed $10 billion of that plan.
We find ourselves in the fortunate position of continuing to generate large amounts of cash, including $23 billion in cash flow from operations in the last quarter alone.
Apple's management team and Board of Directors have been in active discussions about returning additional cash to shareholders. As part of our review, we will thoroughly evaluate Greenlight Capital's current proposal to issue some form of preferred stock. We welcome Greenlight's views and the views of all of our shareholders.
As a part of our efforts to further enhance corporate governance and serve our shareholders' best interests, Proposal 2 in our proxy includes some recommended changes to our articles of incorporation. These changes were recommended independently of Greenlight's proposal and would not preclude Apple from adopting their concept. Contrary to Greenlight's statements, adoption of Proposal 2 would not prevent the issuance of preferred stock.As Appl said, currently, Apple's articles of incorporation provide for the issuance of "blank check" preferred stock by the Board of Directors without shareholder approval. If Proposal 2 is adopted, our shareholders would have the right to approve the issuance of preferred stock. As such, Proposal 2 has the support of many of our shareholders.


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Future Drug Therapy For Inherited Kidney Disease
Scientists at UC Santa Barbara have discovered that patients with an inherited kidney disease may be helped by a drug that is currently available for other uses. The findings are published in this week's issue of the Proceedings of the National Academy of Sciences.
Over 600,000 people in the U.S., and 12 million worldwide, are affected by the inherited kidney disease known as autosomal-dominant polycystic kidney disease (ADPKD). The disease is characterized by the proliferation of thousands of cysts that eventually debilitate the kidneys, causing kidney failure in half of all patients by the time they reach age 50. ADPKD is one of the leading causes of renal failure in the U.S.
"Currently, no treatment exists to prevent or slow cyst formation, and most ADPKD patients require kidney transplants or lifelong dialysis for survival," said Thomas Weimbs, director of the laboratory at UCSB where the discovery was made. Weimbs is an associate professor in the Department of Molecular, Cellular and Developmental Biology, and in the Neuroscience Research Institute at UCSB.
Recent work in the Weimbs laboratory has revealed a key difference between kidney cysts and normal kidney tissue. They found that the STAT6 signaling pathway – previously thought to be mainly important in immune cells – is activated in kidney cysts, while it is dormant in normal kidneys. Cystic kidney cells are locked in a state of continuous activation of this pathway, which leads to the excessive proliferation and cyst growth in ADPKD.
The drug Leflunomide, which is clinically approved for use in rheumatoid arthritis, has previously been shown to inhibit the STAT6 pathway in cells. Weimbs and his team found that Leflunomide is also highly effective in reducing kidney cyst growth in a mouse model of ADPKD.
"These results suggest that the STAT6 pathway is a promising drug target for possible future therapy of ADPKD," said Weimbs. "This possibility is particularly exciting because drugs that inhibit the STAT6 pathway already exist, or are in active development."


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