Attrition, physical integrity and insecticidal activity of long-lasting insecticidal nets in sub-Saharan Africa and modelling of their impact on vectorial capacity.

BACKGROUND: Long-lasting insecticidal nets (LLINs) are the primary malaria prevention and control intervention in many parts of sub-Saharan Africa. While LLINs are expected to last at least 3 years under normal use conditions, they can lose effectiveness because they fall out of use, are discarded, repurposed, physically damaged, or lose insecticidal activity. The contributions of these different interrelated factors to durability of nets and their protection against malaria have been unclear. METHODS: Starting in 2009, LLIN durability studies were conducted in seven countries in Africa over 5 years. WHO-recommended measures of attrition, LLIN use, insecticidal activity, and physical integrity were recorded for eight different net brands. These data were combined with analyses of experimental hut data on feeding inhibition and killing effects of LLINs on both susceptible and pyrethroid resistant malaria vectors to estimate the protection against malaria transmission-in terms of vectorial capacity (VC)-provided by each net cohort over time. Impact on VC was then compared in hypothetical scenarios where one durability outcome measure was set at the best possible level while keeping the others at the observed levels. RESULTS: There was more variability in decay of protection over time by country than by net brand for three measures of durability (ratios of variance components 4.6, 4.4, and 1.8 times for LLIN survival, use, and integrity, respectively). In some countries, LLIN attrition was slow, but use declined rapidly. Non-use of LLINs generally had more effect on LLIN impact on VC than did attrition, hole formation, or insecticide loss. CONCLUSIONS: There is much more variation in LLIN durability among countries than among net brands. Low levels of use may have a larger impact on effectiveness than does variation in attrition or LLIN degradation. The estimated entomological effects of chemical decay are relatively small, with physical decay probably more important as a driver of attrition and non-use than as a direct cause of loss of effect. Efforts to maximize LLIN impact in operational settings should focus on increasing LLIN usage, including through improvements in LLIN physical integrity. Further research is needed to understand household decisions related to LLIN use, including the influence of net durability and the presence of other nets in the household.

How much flower-rich habitat is enough for wild pollinators? Answering a key policy question with incomplete knowledge.

In 2013, an opportunity arose in England to develop an agri-environment package for wild pollinators, as part of the new Countryside Stewardship scheme launched in 2015. It can be understood as a 'policy window', a rare and time-limited opportunity to change policy, supported by a narrative about pollinator decline and widely supported mitigating actions. An agri-environment package is a bundle of management options that together supply sufficient resources to support a target group of species. This paper documents information that was available at the time to develop such a package for wild pollinators. Four questions needed answering: (1) Which pollinator species should be targeted? (2) Which resources limit these species in farmland? (3) Which management options provide these resources? (4) What area of each option is needed to support populations of the target species? Focussing on wild bees, we provide tentative answers that were used to inform development of the package. There is strong evidence that floral resources can limit wild bee populations, and several sources of evidence identify a set of agri-environment options that provide flowers and other resources for pollinators. The final question could only be answered for floral resources, with a wide range of uncertainty. We show that the areas of some floral resource options in the basic Wild Pollinator and Farmland Wildlife Package (2% flower-rich habitat and 1 km flowering hedgerow), are sufficient to supply a set of six common pollinator species with enough pollen to feed their larvae at lowest estimates, using minimum values for estimated parameters where a range was available. We identify key sources of uncertainty, and stress the importance of keeping the Package flexible, so it can be revised as new evidence emerges about how to achieve the policy aim of supporting pollinators on farmland.

How do Australian osteopaths manage migraines? Outcomes from a national practice-based research network.

BACKGROUND: Individuals who experience migraines often seek out a variety of treatment options including manual or physical therapy. Evidence suggests that manual therapy, including osteopathy, can play a role in the management of migraines. Whilst there is some literature on the role osteopathy therapy plays in migraine management, none describes the treatment approaches used by practitioners. OBJECTIVES: To explore the demographic, practice and clinical management characteristics of Australian osteopaths who report treating migraine 'often' in clinical practice. METHODS: Secondary analysis of a cross-sectional survey of 988 osteopaths from the Osteopathy Research and Innovation Network (ORION), an Australian practice-based research network. Regression analysis was used to identify demographic, practice and clinical management characteristics of Australian osteopaths who reported 'often' treating migraine patients. RESULTS: Over 40% of respondents (n = 400) indicated treating patients with migraines 'often'. These osteopaths were less likely to be involved in research and be co-located with a dietician compared to osteopaths who do 'not often' treat migraine. Osteopaths who reported 'often' treating migraine were: five times as likely to treat non-English speaking ethnic groups; 2.5 times as likely to treat chronic pain, temporomandibular joint disorders and hand musculoskeletal complaints; compared to those that do not treat migraines 'often'. CONCLUSION: Australian osteopaths who treat migraine are five times more likely to treat non-English speaking ethnic groups; twice as likely to treat chronic pain; temporomandibular joint disorders, and hand musculoskeletal complaints. More research is needed to identify the practices and patient outcomes associated with osteopathy care for those experiencing migraines.

Association of dynamic contrast-enhanced MRI and 18F-Fluorodeoxyglucose PET/CT parameters with neoadjuvant therapy response and survival in esophagogastric cancer.

INTRODUCTION: Better predictive markers are needed to deliver individualized care for patients with primary esophagogastric cancer. This exploratory study aimed to assess whether pre-treatment imaging parameters from dynamic contrast-enhanced MRI and 18F-fluorodeoxyglucose (18F-FDG) PET/CT are associated with response to neoadjuvant therapy or outcome. MATERIALS AND METHODS: Following ethical approval and informed consent, prospective participants underwent dynamic contrast-enhanced MRI and 18F-FDG PET/CT prior to neoadjuvant chemotherapy/chemoradiotherapy ± surgery. Vascular dynamic contrast-enhanced MRI and metabolic 18F-FDG PET parameters were compared by tumor characteristics using Mann Whitney U test and with pathological response (Mandard tumor regression grade), recurrence-free and overall survival using logistic regression modelling, adjusting for predefined clinical variables. RESULTS: 39 of 47 recruited participants (30 males; median age 65 years, IQR: 54, 72 years) were included in the final analysis. The tumor vascular-metabolic ratio was higher in patients remaining node positive following neoadjuvant therapy (median tumor peak enhancement/SUVmax ratio: 0.052 vs. 0.023, p = 0.02). In multivariable analysis adjusted for age, gender, pre-treatment tumor and nodal stage, peak enhancement (highest gadolinium concentration value prior to contrast washout) was associated with pathological tumor regression grade. The odds of response decreased by 5% for each 0.01 unit increase (OR 0.95; 95% CI: 0.90, 1.00, p = 0.04). No 18F-FDG PET/CT parameters were predictive of pathological tumor response. No relationships between pre-treatment imaging and survival were identified. CONCLUSION: Pre-treatment esophagogastric tumor vascular and metabolic parameters may provide additional information in assessing response to neoadjuvant therapy.

Ten-year follow-up of SpA-related oligoarthritis involving the knee: the presence of psoriasis but not HLA-B27 or baseline MRI bone oedema predicts outcome.

OBJECTIVE: Bone marrow oedema (BMO) and HLA-B27 are poor prognostic factors in axial SpA, and psoriasis is a poor prognostic factor in small-joint polyarthropathy. The aim of this study was to investigate the influence of HLA-B27, MRI BMO and psoriasis on long-term outcomes in early SpA-related knee joint oligoarthritis. METHODS: Patients with SpA-related oligoarthritis with knee involvement were recruited. Baseline assessment included ESSG criteria, RF, HLA-B27 and MRI. The degree of MRI BMO was determined on fat-suppression sequences and scored using the whole-organ magnetic resonance imaging score (WORMS) (range 0-45). Patients were treated at the discretion of their rheumatologist and followed up for 10 years. Outcome assessments included joint counts, functional and symptomatic questionnaire, CRP and radiographic assessment for OA. RESULTS: Forty-four patients were recruited [mean age 32 years (range 15-59 years), 70% male] with a mean disease duration at baseline of 9.75 months (1-48 months). Twenty-six (59%) patients (mean age 43 years, 65% male) returned for follow-up after a mean of 10 years (range 8.4-12.6 years). Ten (38%) patients had persistent clinical synovitis and 31% of knees had secondary radiographic OA. Global outcome was poor/very poor in 69% of cases. The only factor predicting outcome at 10 years was psoriasis, but neither HLA-B27 nor BMO. PsA patients had significantly worse global outcome compared with ReA (P = 0.036), and significantly worse symptomatic (P = 0.001) and functional (P = 0.001) outcome compared with other subtypes. CONCLUSION: SpA-related knee joint oligoarthritis has significant long-term clinical and radiological morbidity despite standard treatments. HLA-B27 and MRI BMO were not predictors of poor outcome as they are in axial SpA; however, the presence of psoriasis predicted significantly worse outcome.

A Large Cluster of New Onset Autoimmune Myositis in the Yorkshire Region Following SARS-CoV-2 Vaccination.

BACKGROUND: The novel SARS-CoV-2 vaccines partially exploit intrinsic DNA or RNA adjuvanticity, with dysregulation in the metabolism of both these nucleic acids independently linked to triggering experimental autoimmune diseases, including lupus and myositis. METHODS: Herein, we present 15 new onset autoimmune myositis temporally associated with SARS-CoV-2 RNA or DNA-based vaccines that occurred between February 2021 and April 2022. Musculoskeletal, pulmonary, cutaneous and cardiac manifestations, laboratory and imaging data were collected. RESULTS: In total, 15 cases of new onset myositis (11 polymyositis/necrotizing/overlap myositis; 4 dermatomyositis) were identified in the Yorkshire region of approximately 5.6 million people, between February 2021 and April 2022 (10 females/5 men; mean age was 66.1 years; range 37-83). New onset disease occurred after first vaccination (5 cases), second vaccination (7 cases) or after the third dose (3 cases), which was often a different vaccine. Of the cases, 6 had systemic complications including skin (3 cases), lung (3 cases), heart (2 cases) and 10/15 had myositis associated autoantibodies. All but 1 case had good therapy responses. Adverse event following immunization (AEFI) could not be explained based on the underlying disease/co-morbidities. CONCLUSION: Compared with our usual regional Rheumatology clinical experience, a surprisingly large number of new onset myositis cases presented during the period of observation. Given that antigen release inevitably follows muscle injury and given the role of nucleic acid adjuvanticity in autoimmunity and muscle disease, further longitudinal studies are required to explore potential links between novel coronavirus vaccines and myositis in comparison with more traditional vaccine methods.

Highly regioselective anti-markovnikov palladium-borate-catalyzed methoxycarbonylation reactions: unprecedented results for aryl olefins.

[Structure: see text] A general, highly efficient and regioselective methoxycarbonylation, by means of a palladium-salicylicborate-catalyzed protocol, of terminal alkyl and aryl olefins is described. The substrates include aliphatic alkenes, allylbenzenes, and styrene derivatives. The yields are very good (60-92%) and the regioselectivity, in favor of the linear ester, is up to quantitative--unprecedented in the case of styrenes.

Surgical approaches to vascular access for large-caliber devices in preclinical research models.

Percutaneous vascular access options in preclinical models are often smaller than the relevant structures in humans or undersized for early-prototype research devices. Here we describe the surgical approaches and results for surgical vascular access sites in preclinical swine and sheep models. Fourteen adult miniature swine underwent successful 18-French vascular access by means of thoracotomy to the brachiocephalic artery. In addition, 11 swine and 10 sheep underwent successful 22-French vascular access by means of retroperitoneal laparotomy to the abdominal aorta. The relevancy of approach angles and vessel tortuosity should be considered when selecting appropriate preclinical models and techniques. The techniques described are effective for delivery of large-caliber devices in preclinical testing.

Ileal oxalate absorption and urinary oxalate excretion are enhanced in Slc26a6 null mice.

Intestinal oxalate transport, mediated by anion exchange proteins, is important to oxalate homeostasis and consequently to calcium oxalate stone diseases. To assess the contribution of the putative anion transporter (PAT)1 (Slc26a6) to transepithelial oxalate transport, we compared the unidirectional and net fluxes of oxalate across isolated, short-circuited segments of the distal ileum of wild-type (WT) mice and Slc26a6 null mice [knockout (KO)]. Additionally, urinary oxalate excretion was measured in both groups. In WT mouse ileum, there was a small net secretion of oxalate (J(net)(Ox) = -5.0 +/-5.0 pmol.cm(-2).h(-1)), whereas in KO mice J(net)(Ox) was significantly absorptive (75 +/- 10 pmol.cm(-2)h.h(-1)), which was the result of a smaller serosal-to-mucosal oxalate flux (J(sm)(Ox)) and a larger mucosal-to-serosal oxalate flux (J(ms)(Ox)). Mucosal DIDS (200 microM) reduced J(sm)(Ox) in WT mice, leading to reversal of the direction of net oxalate transport from secretion to absorption (J(net)(Ox) = 15.0 +/- 5.0 pmol.cm(-2).h(-1)) , but DIDS had no significant effect on KO ileum. In WT mice in the absence of mucosal Cl(-), there were small increases in J(ms)(Ox) and decreases in J(sm)(Ox) that led to a small net oxalate absorption. In KO mice, J(net)(Ox) was 1.5-fold greater in the absence of mucosal Cl(-), due solely to an increase in J(ms)(Ox). Urinary oxalate excretion was about fourfold greater in KO mice compared with WT littermates. We conclude that PAT1 is DIDS sensitive and mediates a significant fraction of oxalate efflux across the apical membrane in exchange for Cl(-); as such, PAT1 represents a major apical membrane pathway mediating J(sm)(Ox).

Effects of diet and metamorphosis upon the sterol composition of the butterfly Morpho peleides.

Whole body sterol metabolism in insects has seldom been studied. We were able to design an appropriate study at a butterfly farm in Belize. We collected six larvas of butterfly (Morpho peleides), their food (leaves of Pterocarpus bayessii), and their excretions. In addition, six adult butterflies were collected. The sterols of the diet, the larva, and adult butterfly were analyzed by gas-liquid chromatography. The structures of these sterols were identified by digitonin precipitation, GC-MS, and NMR. Four sterols (cholesterol, campesterol, stigmasterol, and sitosterol) and a sterol mixture were found in the food, the body, and the excreta of the larva. The tissue sterol content of the larva was 326 microg. They consumed 276 microg of sterols per day. Their excretion was 185 microg per day as sterols. The total tissue sterol contents of the larva and butterfly were similar, but they had different sterol compositions, which indicated interconversion of sterols during development. There was a progressive increase in the cholesterol content from larva to butterfly and a decrease in the content of sitosterol and other plant sterols, which were likely converted to cholesterol. Our data indicated an active sterol metabolism in butterfly larva. Diet played an important role in determining its sterol composition. During metamorphosis, there was an interconversion of sterols. This is the first paper documenting the fecal sterol excretion in insects as related to dietary intakes.