Choosing Organic Pesticides over Synthetic Pesticides May Not Effectively Mitigate Environmental Risk in Soybeans

Background: Selection of pesticides with small ecological footprints is a key factor in developing sustainable agricultural systems. Policy guiding the selection of pesticides often emphasizes natural products and organic-certified pesticides to increase sustainability, because of the prevailing public opinion that natural products are uniformly safer, and thus more environmentally friendly, than synthetic chemicals. Methodology/Principal Findings: We report the results of a study examining the environmental impact of several new synthetic and certified organic insecticides under consideration as reduced-risk insecticides for soybean aphid (Aphis glycines) control, using established and novel methodologies to directly quantify pesticide impact in terms of biocontrol services. We found that in addition to reduced efficacy against aphids compared to novel synthetic insecticides, organic approved insecticides had a similar or even greater negative impact on several natural enemy species in lab studies, were more detrimental to biological control organisms in field experiments, and had higher Environmental Impact Quotients at field use rates. Conclusions/Significance: These data bring into caution the widely held assumption that organic pesticides are more environmentally benign than synthetic ones. All pesticides must be evaluated using an empirically-based risk assessment

The socio-technical organisation of community pharmacies as a factor in the Electronic Prescription Service Release Two implementation: a qualitative study

Background The introduction of a new method of transmitting prescriptions from general practices to community pharmacies in England (Electronic Prescription Service Release 2 (EPS2)) has generated debate on how it will change work practice. As EPS2 will be a key technical element in dispensing, we reviewed the literature to find that there were no studies on how social and technical elements come together to form work practice in community pharmacies. This means the debate has little point of reference. Our aim therefore was to study the ways social and technical elements of a community pharmacy are used to achieve dispensing through the development of a conceptual model on pharmacy work practice, and to consider how a core technical element such the EPS2 could change work practice. Method We used ethnographic methods inclusive of case-study observations and interviews to collect qualitative data from 15 community pharmacies that were in the process of adopting or were soon to adopt EPS2. We analysed the case studies thematically and used rigorous multi-dimensional and multi-disciplinary interpretive validation techniques to cross analyse findings. Results In practice, dispensing procedures were not designed to take into account variations in human and technical integration, and assumed that repetitive and collective use of socio-technical elements were at a constant. Variables such as availability of social and technical resources, and technical know-how of staff were not taken into account in formalised procedures. Yet community pharmacies were found to adapt their dispensing in relation to the balance of social and technical elements available, and how much of the social and technical elements they were willing to integrate into dispensing. While some integrated as few technical elements as possible, some depended entirely on technical artefacts. This pattern also applied to the social elements of dispensing. Through the conceptual model development process, we identified three approaches community pharmacies used to appropriate procedures in practice. These were ‘technically oriented’, ‘improvising’ or ‘socially oriented’. Conclusion We offer a model of different work approaches community pharmacies use to dispense, which suggests that when adopting a core technical element such as the EPS2 system of dispensing there could be variations in its successful adoption. Technically oriented pharmacies might find it easiest to integrate a similar artefact into work practice although needs EPS2 to synchronise effectively with existing technologies. Pharmacies adopting an improvising-approach have the potential to improve how they organise dispensing through EPS2 although they will need to improve how they apply their operating procedures. Socially oriented pharmacies will need to dramatically adapt their approach to dispensing since they usually rely on few technical tools

An integrated model of care to counter high incidence of HIV and sexually transmitted diseases in men who have sex with men – initial analysis of service utilizers in Zurich

BACKGROUND: As other countries, Switzerland experiences a high or even rising incidence of HIV and sexually transmitted infections (STI) among men who have sex with men (MSM). An outpatient clinic for gay men ("Checkpoint") was opened in 2006 in Zurich (Switzerland) in order to provide sexual health services. The clinic provides counselling, testing, medical treatment and follow-up at one location under an "open-door-policy" and with a high level of personal continuity. We describe first experiences with the new service and report the characteristics of the population that utilized it. METHODS: During the 6-month evaluation period, individuals who requested counselling, testing or treatment were asked to participate in a survey at their first visit prior to the consultation. The instrument includes questions regarding personal data, reasons for presenting, sexual behaviour, and risk situations. Number and results of HIV/STI tests and treatments for STI were also recorded. RESULTS: During the evaluation period, 632 consultations were conducted and 247 patients were seen by the physician. 406 HIV tests were performed (3.4% positive). 402 men completed the entry survey (64% of all consultations). The majority of respondents had 4 and more partners during the last 12 months and engaged in either receptive, insertive or both forms of anal intercourse. More than half of the responders used drugs or alcohol to get to know other men or in conjunction with sexual activity (42% infrequently, 10% frequently and 0.5% used drugs always). The main reasons for requesting testing were a prior risk situation (46.3%), followed by routine screening without a prior risk situation (24.1%) and clarification of HIV/STI status due to a new relationship (29.6%). A fifth of men that consulted the service had no history of prior tests for HIV or other STIs. CONCLUSION: Since its first months of activity, the service achieved high levels of recognition, acceptance and demand in the MSM community. Contrary to common concepts of "testing clinics", the Checkpoint service provides post-exposure prophylaxis, HIV and STI treatment, psychological support and counselling and general medical care. It thus follows a holistic approach to health in the MSM community with the particular aim to serve as a "door opener" between the established system of care and those men that have no access to, or for any reason hesitate to utilize traditional health care

The mutational impact of culturing human pluripotent and adult stem cells

Genetic changes acquired during in vitro culture pose a risk for the successful application of stem cells in regenerative medicine. To assess the genetic risks induced by culturing, we determined all mutations in individual human stem cells by whole genome sequencing. Individual pluripotent, intestinal, and liver stem cells accumulate 3.5 ± 0.5, 7.2 ± 1.1 and 8.3 ± 3.6 base substitutions per population doubling, respectively. The annual in vitro mutation accumulation rate of adult stem cells is nearly 40-fold higher than the in vivo mutation accumulation rate. Mutational signature analysis reveals that in vitro induced mutations are caused by oxidative stress. Reducing oxygen tension in culture lowers the mutational load. We use the mutation rates, spectra, and genomic distribution to model the accumulation of oncogenic mutations during typical in vitro expansion, manipulation or screening experiments using human stem cells. Our study provides empirically defined parameters to assess the mutational risk of stem cell based therapies

Anti-Human Tissue Factor Antibody Ameliorated Intestinal Ischemia Reperfusion-Induced Acute Lung Injury in Human Tissue Factor Knock-In Mice

BACKGROUND: Interaction between the coagulation and inflammation systems plays an important role in the development of acute respiratory distress syndrome (ARDS). Anti-coagulation is an attractive option for ARDS treatment, and this has promoted development of new antibodies. However, preclinical trials for these antibodies are often limited by the high cost and availability of non-human primates. In the present study, we developed a novel alternative method to test the role of a humanized anti-tissue factor mAb in acute lung injury with transgenic mice. METHODOLOGY/PRINCIPAL FINDINGS: Human tissue factor knock-in (hTF-KI) transgenic mice and a novel humanized anti-human tissue factor mAb (anti-hTF mAb, CNTO859) were developed. The hTF-KI mice showed a normal and functional expression of hTF. The anti-hTF mAb specifically blocked the pro-coagulation activity of brain extracts from the hTF-KI mice and human, but not from wild type mice. An extrapulmonary ARDS model was used by intestinal ischemia-reperfusion. Significant lung tissue damage in hTF-KI mice was observed after 2 h reperfusion. Administration of CNTO859 (5 mg/kg, i.v.) attenuated the severity of lung tissue injury, decreased the total cell counts and protein concentration in bronchoalveolar lavage fluid, and reduced Evans blue leakage. In addition, the treatment significantly reduced alveolar fibrin deposition, and decreased tissue factor and plasminogen activator inhibitor-1 activity in the serum. This treatment also down-regulated cytokine expression and reduced cell death in the lung. CONCLUSIONS: This novel anti-hTF antibody showed beneficial effects on intestinal ischemia-reperfusion induced acute lung injury, which merits further investigation for clinical usage. In addition, the use of knock-in transgenic mice to test the efficacy of antibodies against human-specific proteins is a novel strategy for preclinical studies

Core Outcomes for Colorectal Cancer Surgery: A Consensus Study

Background: Colorectal cancer (CRC) is a major cause of worldwide morbidity and mortality. Surgical treatment is common, and there is a great need to improve the delivery of such care. The gold standard for evaluating surgery is within well-designed randomized controlled trials (RCTs); however, the impact of RCTs is diminished by a lack of coordinated outcome measurement and reporting. A solution to these issues is to develop an agreed standard “core” set of outcomes to be measured in all trials to facilitate cross-study comparisons, meta-analysis, and minimize outcome reporting bias. This study defines a core outcome set for CRC surgery. Methods and Findings: The scope of this COS includes clinical effectiveness trials of surgical interventions for colorectal cancer. Excluded were nonsurgical oncological interventions. Potential outcomes of importance to patients and professionals were identified through systematic literature reviews and patient interviews. All outcomes were transcribed verbatim and categorized into domains by two independent researchers. This informed a questionnaire survey that asked stakeholders (patients and professionals) from United Kingdom CRC centers to rate the importance of each domain. Respondents were resurveyed following group feedback (Delphi methods). Outcomes rated as less important were discarded after each survey round according to predefined criteria, and remaining outcomes were considered at three consensus meetings; two involving international professionals and a separate one with patients. A modified nominal group technique was used to gain the final consensus. Data sources identified 1,216 outcomes of CRC surgery that informed a 91 domain questionnaire. First round questionnaires were returned from 63 out of 81 (78%) centers, including 90 professionals, and 97 out of 267 (35%) patients. Second round response rates were high for all stakeholders (>80%). Analysis of responses lead to 45 and 23 outcome domains being retained after the first and second surveys, respectively. Consensus meetings generated agreement on a 12 domain COS. This constituted five perioperative outcome domains (including anastomotic leak), four quality of life outcome domains (including fecal urgency and incontinence), and three oncological outcome domains (including long-term survival). Conclusion: This study used robust consensus methodology to develop a core outcome set for use in colorectal cancer surgical trials. It is now necessary to validate the use of this set in research practice

Pneumococcal polysaccharide vaccination in adults undergoing immunosuppressive treatment for inflammatory diseases - a longitudinal study.

INTRODUCTION: Patients undergoing immunosuppressive therapy are at increased risk of infection. Community-acquired pneumonia and invasive pneumococcal disease account for substantial morbidity and mortality in this population and may be prevented by vaccination. Ideally, immunization to pneumococcal antigens should take place before the start of immunosuppressive treatment. Often, however, the treatment cannot be delayed. Little is known about the efficacy of pneumococcal vaccines during immunosuppressive treatment. The objectives of this study were to determine the percentage of vaccine-naïve, immunosuppressed adults with inflammatory diseases seroprotected against Streptococcus pneumoniae and to assess factors associated with the immunogenicity, clinical impact and safety of 23-valent pneumococcal polysaccharide vaccine (PPV) in seronegative subjects. METHODS: This observational study included patients 18 years of age and older who were receiving prednisone ≥20 mg/day or other immunosuppressive drugs. Exclusion criteria were PPV administration in the previous 5 years, intravenous immunoglobulins and pregnancy. Serum immunoglobulin G (IgG) antibody levels against six pneumococcal serotypes were measured. Seropositivity was defined as IgG of 0.5 μg/ml or greater for at least four of six serotypes. Seronegative patients received PPV, and seropositive patients were included as a comparison group. Vaccine response and tolerance were assessed after 4-8 weeks. Disease activity was evaluated on the basis of the Physician Global Assessment scores. Serology was repeated after 1 year, and information on any kind of infection needing medical attention was collected. Outcomes were the proportion of seropositivity and infections between vaccinated and unvaccinated patients. RESULTS: Of 201 included patients, 35 received high-dose corticosteroids and 181 were given immunosuppressive drugs. Baseline seronegativity in 60 (30 %) patients was associated with corticotherapy and lower total IgG. After PPV, disease activity remained unchanged or decreased in 81 % of patients, and 87 % became seropositive. After 1 year, 67 % of vaccinated compared with 90 % of observed patients were seropositive (p < 0.001), whereas the rate of infections did not differ between groups. Those still taking prednisone ≥10 mg/day tended to have poorer serological responses and had significantly more infections. CONCLUSIONS: PPV was safe and moderately effective based on serological response. Seropositivity to pneumococcal antigens significantly reduced the risk of infections. Sustained high-dose corticosteroids were associated with poor vaccine response and more infections

A systematic review of mental disorder, suicide, and deliberate self harm in lesbian, gay and bisexual people

Background: Lesbian, gay and bisexual (LGB) people may be at higher risk of mental disorders than heterosexual people.Method: We conducted a systematic review and meta-analysis of the prevalence of mental disorder, substance misuse, suicide, suicidal ideation and deliberate self harm in LGB people. We searched Medline, Embase, PsycInfo, Cinahl, the Cochrane Library Database, the Web of Knowledge, the Applied Social Sciences Index and Abstracts, the International Bibliography of the Social Sciences, Sociological Abstracts, the Campbell Collaboration and grey literature databases for articles published January 1966 to April 2005. We also used Google and Google Scholar and contacted authors where necessary. We searched all terms related to homosexual, lesbian and bisexual people and all terms related to mental disorders, suicide, and deliberate self harm. We included papers on population based studies which contained concurrent heterosexual comparison groups and valid definition of sexual orientation and mental health outcomes.Results: Of 13706 papers identified, 476 were initially selected and 28 (25 studies) met inclusion criteria. Only one study met all our four quality criteria and seven met three of these criteria. Data was extracted on 214,344 heterosexual and 11,971 non heterosexual people. Meta-analyses revealed a two fold excess in suicide attempts in lesbian, gay and bisexual people [ pooled risk ratio for lifetime risk 2.47 (CI 1.87, 3.28)]. The risk for depression and anxiety disorders (over a period of 12 months or a lifetime) on meta-analyses were at least 1.5 times higher in lesbian, gay and bisexual people (RR range 1.54-2.58) and alcohol and other substance dependence over 12 months was also 1.5 times higher (RR range 1.51-4.00). Results were similar in both sexes but meta analyses revealed that lesbian and bisexual women were particularly at risk of substance dependence (alcohol 12 months: RR 4.00, CI 2.85, 5.61; drug dependence: RR 3.50, CI 1.87, 6.53; any substance use disorder RR 3.42, CI 1.97-5.92), while lifetime prevalence of suicide attempt was especially high in gay and bisexual men (RR 4.28, CI 2.32, 7.88).Conclusion: LGB people are at higher risk of mental disorder, suicidal ideation, substance misuse, and deliberate self harm than heterosexual people

Light regulation of metabolic pathways in fungi

Light represents a major carrier of information in nature. The molecular machineries translating its electromagnetic energy (photons) into the chemical language of cells transmit vital signals for adjustment of virtually every living organism to its habitat. Fungi react to illumination in various ways, and we found that they initiate considerable adaptations in their metabolic pathways upon growth in light or after perception of a light pulse. Alterations in response to light have predominantly been observed in carotenoid metabolism, polysaccharide and carbohydrate metabolism, fatty acid metabolism, nucleotide and nucleoside metabolism, and in regulation of production of secondary metabolites. Transcription of genes is initiated within minutes, abundance and activity of metabolic enzymes are adjusted, and subsequently, levels of metabolites are altered to cope with the harmful effects of light or to prepare for reproduction, which is dependent on light in many cases. This review aims to give an overview on metabolic pathways impacted by light and to illustrate the physiological significance of light for fungi. We provide a basis for assessment whether a given metabolic pathway might be subject to regulation by light and how these properties can be exploited for improvement of biotechnological processes