Achirality in the low temperature structure and lattice modes of tris(acetylacetonate)iron(iii)

Tris(acetylacteonate) iron(III) is a relatively ubiquitous mononuclear inorganic coordination complex. The bidentate nature of the three acetylacteonate ligands coordinating around a single centre inevitably leads to structural isomeric forms, however whether or not this relates to chirality in the solid state has been questioned in the literature. Variable temperature neutron diffraction data down to T = 3 K, highlights the dynamic nature of the ligand environment, including the motions of the hydrogen atoms. The Fourier transform of the molecular dynamics simulation based on the experimentally determined structure was shown to closely reproduce the low temperature vibrational density of states obtained using inelastic neutron scattering

Limited Antigenic Diversity in Contemporary H7 Avian-Origin Influenza A Viruses from North America

Subtype H7 avian–origin influenza A viruses (AIVs) have caused at least 500 confirmed human infections since 2003 and culling of \u3e75 million birds in recent years. Here we antigenically and genetically characterized 93 AIV isolates from North America (85 from migratory waterfowl [1976–2010], 7 from domestic poultry [1971–2012], and 1 from a seal [1980]). The hemagglutinin gene of these H7 viruses are separated from those from Eurasia. Gradual accumulation of nucleotide and amino acid substitutions was observed in the hemagglutinin of H7 AIVs from waterfowl and domestic poultry. Genotype characterization suggested that H7 AIVs in wild birds form diverse and transient internal gene constellations. Serologic analyses showed that the 93 isolates cross-reacted with each other to different extents. Antigenic cartography showed that the average antigenic distance among them was 1.14 units (standard deviation [SD], 0.57 unit) and that antigenic diversity among the H7 isolates we tested was limited. Our results suggest that the continuous genetic evolution has not led to significant antigenic diversity for H7 AIVs from North America. These findings add to our understanding of the natural history of IAVs and will inform public health decision-making regarding the threat these viruses pose to humans and poultry

Daily living skills scale: Development and preliminary validation of a new, open-source assessment of daily living skills

Autistic individuals and individuals with a range of other neurodevelopmental conditions (NDD) often present with lower levels of daily living skills (DLS) when compared to their neurotypical peers. Importantly, lower levels of DLS have been linked to a range of negative outcomes, including lower rates of post-secondary education, lower employment rates, and higher daily support needs across autism and NDD. However, there are currently no open-source informant-reported instruments for capturing key aspects of DLS. This study describes the development, refinement, and initial psychometric evaluation of a new, relatively brief (53-item). Daily Living Skills Scale (DLSS) in a sample of 1,361 children aged 2–17 years, Confirmatory Factor Analysis demonstrated an excellent fit of unidimensional model to the data (CFI = 0.953, TLI = 0.951, RMSEA = 0.073 [95% CI: 0.071–0.074]). The single-factor CFA model showed evidence of measurement invariance of factor loadings, thresholds, and residual variance (strict invariance) across sex, age, race, and ethnicity. Model reliability and internal consistency were excellent (ω = 0.98; α = 0.97). Conditional reliability estimates indicated very good reliability (= 0.80) for the total DLS scale from very low (θ = −4.2) to high (θ = +2.4) scores. Conceptually derived self-care, homecare, and community participation subscales also showed strong reliability and internal consistency. With further replication, the EFS has excellent potential for wide adoption across research and clinical contexts

Widespread detection of highly pathogenic H5 influenza viruses in wild birds from the Pacific Flyway of the United States

A novel highly pathogenic avian influenza virus belonging to the H5 clade 2.3.4.4 variant viruses was detected in North America in late 2014. Motivated by the identification of these viruses in domestic poultry in Canada, an intensive study was initiated to conduct highly pathogenic avian influenza surveillance in wild birds in the Pacific Flyway of the United States. A total of 4,729 hunter-harvested wild birds were sampled and highly pathogenic avian influenza virus was detected in 1.3% (n = 63). Three H5 clade 2.3.4.4 subtypes were isolated from wild birds, H5N2, H5N8, and H5N1, representing the wholly Eurasian lineage H5N8 and two novel reassortant viruses. Testing of 150 additional wild birds during avian morbidity and mortality investigations in Washington yielded 10 (6.7%) additional highly pathogenic avian influenza isolates (H5N8 = 3 and H5N2 = 7). The geographically widespread detection of these viruses in apparently healthy wild waterfowl suggest that the H5 clade 2.3.4.4 variant viruses may behave similarly in this taxonomic group whereby many waterfowl species are susceptible to infection but do not demonstrate obvious clinical disease. Despite these findings in wild waterfowl, mortality has been documented for some wild bird species and losses in US domestic poultry during the first half of 2015 were unprecedented

Acupuncture, Counseling, and Usual care for Depression (ACUDep): study protocol for a randomized controlled trial

Background: The evidence on the effect of acupuncture or counseling for depression is not conclusive yet is sufficient to warrant further research. Our aim is to conduct a full-scale RCT to determine the clinical and cost effectiveness of acupuncture and counseling compared to usual care alone. We will explore the experiences and perspectives of patients and practitioners. Methods/Design: Randomized controlled trial with three parallel arms: acupuncture plus usual care, counseling plus usual care, and usual care alone, in conjunction with a nested qualitative study using in-depth interviews with purposive samples of trial participants. Participants: Patients aged over 18 years diagnosed with depression or mood disorder by their GP and with a score of 20 or above on the Beck Depression Inventory (BDI-II). Randomization: Computer randomization by York Trials Unit to acupuncture, counseling, and usual care alone in proportions of 2:2:1, respectively, with secure allocation concealment. Interventions: Patients allocated to acupuncture and counseling groups receive the offer of up to 12 weekly sessions. Both interventions allow flexibility to address patient variation, yet are constrained within defined protocols. Acupuncture is based on traditional Chinese medicine and counseling is non-directive within the humanistic tradition. Outcome: The PHQ-9 is the primary outcome measure, collected at baseline, 3, 6, 9, and 12 months. Also measured is BDI-II, SF-36 Bodily pain subscale, and EQ-5D. Texted mood scores are collected weekly over the first 15 weeks. Health-related resource use is collected over 12 months. Analysis: The sample size target was for 640 participants, calculated for an effect size of 0.32 on the PHQ-9 when comparing acupuncture with counseling given 90% power, 5% significance, and 20% loss to follow-up. Analysis of covariance will be used on an intention-to-treat basis. Thematic analysis will be used for qualitative data. We will compare incremental cost-effectiveness of the three treatment options at 12 months. Discussion: Ethical approval was obtained in October 2009. There were six subsequent protocol amendments, the last of which was approved in January 2012. Recruitment of 755 participants took place over 18 months. Data collection will be completed by June 2012. No interim analyses have been conducted

Efficiency and safety of varying the frequency of whole blood donation (INTERVAL): a randomised trial of 45 000 donors

Background: Limits on the frequency of whole blood donation exist primarily to safeguard donor health. However, there is substantial variation across blood services in the maximum frequency of donations allowed. We compared standard practice in the UK with shorter inter-donation intervals used in other countries. Methods: In this parallel group, pragmatic, randomised trial, we recruited whole blood donors aged 18 years or older from 25 centres across England, UK. By use of a computer-based algorithm, men were randomly assigned (1:1:1) to 12-week (standard) versus 10-week versus 8-week inter-donation intervals, and women were randomly assigned (1:1:1) to 16-week (standard) versus 14-week versus 12-week intervals. Participants were not masked to their allocated intervention group. The primary outcome was the number of donations over 2 years. Secondary outcomes related to safety were quality of life, symptoms potentially related to donation, physical activity, cognitive function, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin. This trial is registered with ISRCTN, number ISRCTN24760606, and is ongoing but no longer recruiting participants. Findings: 45 263 whole blood donors (22 466 men, 22 797 women) were recruited between June 11, 2012, and June 15, 2014. Data were analysed for 45 042 (99·5%) participants. Men were randomly assigned to the 12-week (n=7452) versus 10-week (n=7449) versus 8-week (n=7456) groups; and women to the 16-week (n=7550) versus 14-week (n=7567) versus 12-week (n=7568) groups. In men, compared with the 12-week group, the mean amount of blood collected per donor over 2 years increased by 1·69 units (95% CI 1·59–1·80; approximately 795 mL) in the 8-week group and by 0·79 units (0·69–0·88; approximately 370 mL) in the 10-week group (p<0·0001 for both). In women, compared with the 16-week group, it increased by 0·84 units (95% CI 0·76–0·91; approximately 395 mL) in the 12-week group and by 0·46 units (0·39–0·53; approximately 215 mL) in the 14-week group (p<0·0001 for both). No significant differences were observed in quality of life, physical activity, or cognitive function across randomised groups. However, more frequent donation resulted in more donation-related symptoms (eg, tiredness, breathlessness, feeling faint, dizziness, and restless legs, especially among men [for all listed symptoms]), lower mean haemoglobin and ferritin concentrations, and more deferrals for low haemoglobin (p<0·0001 for each) than those observed in the standard frequency groups. Interpretation: Over 2 years, more frequent donation than is standard practice in the UK collected substantially more blood without having a major effect on donors' quality of life, physical activity, or cognitive function, but resulted in more donation-related symptoms, deferrals, and iron deficiency. Funding: NHS Blood and Transplant, National Institute for Health Research, UK Medical Research Council, and British Heart Foundation

Association between depressive symptoms and incident cardiovascular diseases

Importance: It is uncertain whether depressive symptoms are independently associated with subsequent risk of cardiovascular diseases (CVD). Objective: To characterize the association between depressive symptoms and CVD incidence across the spectrum of lower mood. Design, setting and participants: A pooled analysis of individual-participant-data from the Emerging Risk Factors Collaboration (ERFC; 162,036 participants; 21 cohorts; baseline surveys, 1960-2008; latest follow-up, March 2020) and UK Biobank (UKB; 401,219 participants; baseline surveys, 2006-2010; latest follow-up, March 2020). Eligible participants had information about self-reported depressive symptoms and no CVD history at baseline. Exposure: Depressive symptoms were recorded using validated instruments. ERFC scores were harmonized across studies to a scale representative of the Centre for Epidemiological Studies Depression scale (CES-D; range 0-60; ≥16 indicates possible depressive disorder). UKB recorded the Patient Health Questionnaire-2 (PHQ-2; range 0-6; ≥3 indicates possible depressive disorder). Main Outcomes and Measures: Primary outcomes were incident fatal/nonfatal coronary heart disease (CHD), stroke and CVD (composite of CHD and stroke). Hazard ratios (HRs) per 1-SD higher log-CES-D or PHQ-2 adjusted for age, sex, smoking and diabetes were reported. Results: Among 162,036 participants from the ERFC, 73% were female, mean (SD) age at baseline was 63 (9) years, and 5,078 CHD and 3,932 stroke events were recorded (median follow-up, 9.5-years). Associations with CHD, stroke and CVD were log-linear. HRs (95%CI) per 1SD higher depression score for CHD, stroke and CVD respectively were 1.07 (1.03-1.11), 1.05 (1.01-1.10), and 1.06 (1.04-1.08). This reflects, 36 versus 29 CHD events, 28 versus 25 stroke events, and 63 versus 54 CVD events per 1000 individuals over 10 years in the highest versus lowest quintile of CES-D (geometric mean CES-D score, 19 versus 1). Among 401,219 participants from the UKB, 55% were female, mean baseline age was 56 (8) years, and 4607 CHD and 3253 stroke events were recorded (median follow-up, 8.1-years). HRs per 1SD higher depression score for CHD, stroke and CVD respectively were 1.11 (1.08-1.14), 1.10 (1.06-1.14) and 1.10 (1.08-1.13). This reflects, 21 versus 14 CHD events, 15 versus 10 stroke events, and 36 versus 25 CVD events per 1000 individuals over 10 years in those with PHQ2 ≥4 versus 0. The magnitude and statistical significance of the HRs were not materially changed after adjustment for additional risk factors. Conclusions and Relevance: In a pooled analysis of 563,255 participants in 22 cohorts, baseline depressive symptoms were associated with CVD incidence, including at symptom levels below the threshold indicative of a depressive disorder. However, the magnitude of associations was modest.Lisa Pennells, Stephen Kaptoge and Sarah Spackman are funded by a British Heart Foundation Programme Grant (RG/18/13/33946). Steven Bell was funded by the National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics (NIHR BTRU-2014-10024). Tom Bolton is funded by the National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics (NIHR BTRU-2014-10024). Angela Wood is supported by a BHF-Turing Cardiovascular Data Science Award and by the EC-Innovative Medicines Initiative (BigData@Heart). John Danesh holds a British Heart Foundation Professorship and a National Institute for Health Research Senior Investigator Award.* *The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care

Formation and physicochemical properties of crystalline and amorphous salts with different stoichiometries formed between ciprofloxacin and succinic acid

YesMulti-ionizable compounds, such as dicarboxylic acids, offer the possibility of forming salts of drugs with multiple stoichiometries. Attempts to crystallize ciprofloxacin, a poorly water-soluble, amphoteric molecule with succinic acid (S) resulted in isolation of ciprofloxacin hemisuccinate (1:1) trihydrate (CHS-I) and ciprofloxacin succinate (2:1) tetrahydrate (CS-I). Anhydrous ciprofloxacin hemisuccinate (CHS-II) and anhydrous ciprofloxacin succinate (CS-II) were also obtained. It was also possible to obtain stoichiometrically equivalent amorphous salt forms, CHS-III and CS-III, by spray drying and milling, respectively, of the drug and acid. Anhydrous CHS and CS had melting points at ∼215 and ∼228 °C, while the glass transition temperatures of CHS-III and CS-III were ∼101 and ∼79 °C, respectively. Dynamic solubility studies revealed the metastable nature of CS-I in aqueous media, resulting in a transformation of CS-I to a mix of CHS-I and ciprofloxacin 1:3.7 hydrate, consistent with the phase diagram. CS-III was observed to dissolve noncongruently leading to high and sustainable drug solution concentrations in water at 25 and 37 °C, with the ciprofloxacin concentration of 58.8 ± 1.18 mg/mL after 1 h of the experiment at 37 °C. This work shows that crystalline salts with multiple stoichiometries and amorphous salts have diverse pharmaceutically relevant properties, including molecular, solid state, and solubility characteristics.Solid State Pharmaceutical Cluster (SSPC), supported by Science Foundation Ireland under grant number 07/SRC/ B1158

Prevalence of Influenza A viruses in wild migratory birds in Alaska: Patterns of variation in detection at a crossroads of intercontinental flyways

<p>Abstract</p> <p>Background</p> <p>The global spread of the highly pathogenic avian influenza H5N1 virus has stimulated interest in a better understanding of the mechanisms of H5N1 dispersal, including the potential role of migratory birds as carriers. Although wild birds have been found dead during H5N1 outbreaks, evidence suggests that others have survived natural infections, and recent studies have shown several species of ducks capable of surviving experimental inoculations of H5N1 and shedding virus. To investigate the possibility of migratory birds as a means of H5N1 dispersal into North America, we monitored for the virus in a surveillance program based on the risk that wild birds may carry the virus from Asia.</p> <p>Results</p> <p>Of 16,797 birds sampled in Alaska between May 2006 and March 2007, low pathogenic avian influenza viruses were detected in 1.7% by rRT-PCR but no highly pathogenic viruses were found. Our data suggest that prevalence varied among sampling locations, species (highest in waterfowl, lowest in passerines), ages (juveniles higher than adults), sexes (males higher than females), date (highest in autumn), and analytical technique (rRT-PCR prevalence = 1.7%; virus isolation prevalence = 1.5%).</p> <p>Conclusion</p> <p>The prevalence of low pathogenic avian influenza viruses isolated from wild birds depends on biological, temporal, and geographical factors, as well as testing methods. Future studies should control for, or sample across, these sources of variation to allow direct comparison of prevalence rates.</p