ANTIGENIC PROPERTIES OF THE TYPE-SPECIFIC SUBSTANCE DERIVED FROM GROUP A HEMOLYTIC STREPTOCOCCI

1. A substance extracted from group A hemolytic streptococcus is described, which induces active immunity in mice, and in rabbits gives rise to precipitins and to protective antibodies passively transferable to mice. 2. The active immunity in mice is principally type-specific, but some degree of non-type-specific immunity is also developed. The passively transferable protective antibodies are type-specific with only a slight suggestion of non-type specificity. In the precipitin test, the rabbit immune sera give both type-specific and non-type-specific reactions which have not been fully analyzed serologically. 3. Substances contained in the extract absorb the protective antibodies from the serum of rabbits immunized with whole hemolytic streptococci. 4. The most satisfactory method of extraction so far developed is fully described. Chemical tests on the material are consistent with the presence of protein and nucleic acid. 5. The type-specific M substance, prepared as previously described, was compared in some of its antigenic properties with the above mentioned substance. It was found capable of inducing active immunity in mice and of absorbing protective antibody from anti-bacterial immune serum in a manner qualitatively similar to that obtained with the preparations made by the newer methods.     

Factors associated with 5-year risk of hip fracture in postmenopausal women

Context  The 329 000 hip fractures that annually occur in the United States are associated with high morbidity, mortality, and cost. Identification of those at high risk is a step toward prevention. Objective  To develop an algorithm to predict the 5-year risk of hip fracture in postmenopausal women. Design, Setting, and Participants  A total of 93 676 women who participated in the observational component of the Women's Health Initiative (WHI), a multiethnic longitudinal study, were used to develop a predictive algorithm based on commonly available clinical features. Selected factors that predicted hip fracture were then validated by 68 132 women who participated in the clinical trial. The model was tested in a subset of 10 750 women who had undergone dual-energy x-ray absorptiometry (DXA) scans for bone mass density assessment. Main Outcome Measure  The prediction of centrally adjudicated hip fracture, measured by the area under the receiver operator characteristic (ROC) curves. Results  During a mean (SD) follow-up of 7.6 (1.7) years, 1132 hip fractures were identified among women participating in the observational study (annualized rate, 0.16%), whereas during a mean follow-up of 8.0 (1.7) years, 791 hip fractures occurred among women participating in the clinical trial (annualized rate, 0.14%). Eleven factors predicted hip fracture within 5 years: age, self-reported health, weight, height, race/ethnicity, self-reported physical activity, history of fracture after age 54 years, parental hip fracture, current smoking, current corticosteroid use, and treated diabetes. Receiver operating characteristic curves showed that the algorithm had an area under the curve of 80% (95% confidence interval [CI], 0.77%-0.82%) when tested in the cohort of different women who were in the clinical trial. A simplified point score was developed for the probability of hip fracture. Receiver operating characteristic curves comparing DXA-scan prediction based on a 10% subset of the cohort and the algorithm among those who participated the clinical trial were similar, with an area under the curve of 79% (95% CI, 73%-85%) vs 71% (95% CI, 66%-76%). Conclusion  This algorithm, based on 11 clinical factors, may be useful to predict the 5-year risk of hip fracture among postmenopausal women of various ethnic backgrounds. Further studies are needed to assess the clinical implication of the algorithm in general and specifically to identify treatment benefits.      

Availability of Safe Childbirth Supplies in 284 Facilities in Uttar Pradesh,India

Maternal and Child Health Journal - Objectives Vital to implementation of the World Health Organization (WHO) Safe Childbirth Checklist (SCC), designed to improve delivery of 28 essential birth...     

The impact of rapport on intelligence yield: police source handler telephone interactions with covert human intelligence sources

Covert Human Intelligence Sources (CHIS) provide unique access to criminals and organised crime groups, and their collection of intelligence is vital to understanding England and Wales’ threat picture. Rapport is essential to the establishment and maintenance of effective professional relationships between source handlers and their CHIS. Thus, rapport-based interviewing is a fundamental factor to maximising intelligence yield. The present research gained unprecedented access to 105 real-life audio recorded telephone interactions between England and Wales police source handlers and CHIS. This research quantified both the rapport component behaviours (e.g., attention, positivity, and coordination) displayed by the source handler and the intelligence yielded from the CHIS, in order to investigate the frequencies of these rapport components and their relationship to intelligence yield. Overall rapport, attention and coordination significantly correlated with intelligence yield, while positivity did not. Attention was the most frequently used component of rapport, followed by positivity, and then coordination.Key words: Covert Human Intelligence Source, human intelligence, HUMINT, intelligence, interviewing, rapport, source handler     

Increased amygdala and decreased frontolimbic r esting- s tate functional connectivity in children with aggressive behavior

Childhood maladaptive aggression is associated with disrupted functional connectivity within amygdala-prefrontal circuitry. In this study, neural correlates of childhood aggression were probed using the intrinsic connectivity distribution, a voxel-wise metric of global resting-state brain connectivity. This sample included 38 children with aggressive behavior (26 boys, 12 girls) ages 8–16 years and 21 healthy controls (14 boys, 6 girls) matched for age and IQ. Functional MRI data were acquired during resting state, and differential patterns of intrinsic functional connectivity were tested in a priori regions of interest implicated in the pathophysiology of aggressive behavior. Next, correlational analyses tested for associations between functional connectivity and severity of aggression measured by the Reactive-Proactive Aggression Questionnaire in children with aggression. Children with aggressive behavior showed increased global connectivity in the bilateral amygdala relative to controls. Greater severity of aggressive behavior was associated with decreasing global connectivity in the dorsal anterior cingulate and ventromedial prefrontal cortex. Follow-up seed analysis revealed that aggression was also positively correlated with left amygdala connectivity with the dorsal anterior cingulate, ventromedial and dorsolateral prefrontal cortical regions. These results highlight the potential role of connectivity of the amygdala and medial prefrontal and anterior cingulate cortices in modulating the severity of aggressive behavior in treatment-seeking children.     

Exploring the Utility of Recombinant Snake Venom Serine Protease Toxins as Immunogens for Generating Experimental Snakebite Antivenoms

Snakebite is a neglected tropical disease that causes high rates of global mortality and morbidity. Although snakebite can cause a variety of pathologies in victims, haemotoxic effects are particularly common and are typically characterised by haemorrhage and/or venom-induced consumption coagulopathy. Despite polyclonal antibody-based antivenoms being the mainstay life-saving therapy for snakebite, they are associated with limited cross-snake species efficacy, as there is often extensive toxin variation between snake venoms, including those used as immunogens for antivenom production. This restricts the therapeutic utility of any antivenom to certain geographical regions. In this study, we explored the feasibility of using recombinantly expressed toxins as immunogens to stimulate focused, pathology-specific, antibodies in order to broadly counteract specific toxins associated with snakebite envenoming. Three snake venom serine proteases (SVSP) toxins, sourced from geographically diverse and medically important viper snake venoms, were successfully expressed in HEK293F mammalian cells and used for murine immunisation. Analyses of the resulting antibody responses revealed that ancrod and RVV-V stimulated the strongest immune responses, and that experimental antivenoms directed against these recombinant SVSP toxins, and a mixture of the three different immunogens, extensively recognised and exhibited immunological binding towards a variety of native snake venoms. While the experimental antivenoms showed some reduction in abnormal clotting parameters stimulated by the toxin immunogens and crude venom, specifically reducing the depletion of fibrinogen levels and prolongation of prothrombin times, fibrinogen degradation experiments revealed that they broadly protected against venom- and toxin-induced fibrinogenolytic functional activities. Overall, our findings further strengthen the case for the use of recombinant venom toxins as supplemental immunogens to stimulate focused and desirable antibody responses capable of neutralising venom-induced pathological effects, and therefore potentially circumventing some of the limitations associated with current snakebite therapies.     

Insights into Genetic Characteristics and Virological Features of Endemic Avian Influenza A (H9N2) Viruses in Egypt from 2017–2021

From 2010 to 2013, genotype I avian influenza A(H9N2) viruses of the G1-lineage were isolated from several poultry species in Egypt. In 2014, novel reassortant H9N2 viruses were detected in pigeons designated as genotype II. To monitor the subsequent genetic evolution of Egyptian A(H9N2) viruses, we characterized the full genomes of 173 viruses isolated through active surveillance from 2017 to 2022. In addition, we compared the virological characteristics and pathogenicity of representative viruses. Phylogenetic analysis of the HA indicated that all studied sequences from 2017–2021 were grouped into G1-like H9N2 viruses previously detected in Egypt. Phylogenetic analysis indicated that the Egyptian A(H9N2) viruses had undergone further reassortment, inheriting four genes (PB2, PB1, PA, NS) from genotype II, with their remaining segments deriving from genotype I viruses (these viruses designated as genotype III). Studying the virological features of the two most dominant genotypes (I and III) of Egyptian H9N2 viruses in vitro and in vivo indicated that both replicated well in mammalian cells, but did not show any clinical signs in chickens, ducks, and mice. Monitoring avian influenza viruses through surveillance programs and understanding the genetic and antigenic characteristics of circulating H9N2 viruses are essential for risk assessment and influenza pandemic preparedness.     

Evolution of a Systematic Approach to Smoking Cessation in Ontario’s Regional Cancer Centres

Smoking cessation after a cancer diagnosis can significantly improve a person’s prognosis, treatment efficacy and safety, and quality of life. In 2012, Cancer Care Ontario (now part of Ontario Health) introduced a Framework for Smoking Cessation, to be implemented for new ambulatory cancer patients at the province’s 14 Regional Cancer Centres (RCCs). Over time, the program has evolved to become more efficient, use data for robust performance management, and broaden its focus to include new patient populations and additional data collection. In 2017, the framework was revised from a 5As to a 3As brief intervention model, along with an opt-out approach to referrals. The revised model was based on emerging evidence, feedback from stakeholders, and an interim program evaluation. Results showed an initial increase in referrals to cessation services. Two indicators (tobacco use screening and acceptance of a referral) are routinely monitored as part of Ontario Health’s system-wide performance management approach, which has been identified as a key driver of change among RCCs. Due to the COVID-19 pandemic, many RCCs reported a decrease in these indicators. RCCs that were able to maintain a high level of smoking cessation activities during the pandemic offer valuable lessons, including the opportunity to swiftly leverage virtual care. Future directions for the program include capturing data on cessation outcomes and expanding the intervention to new populations. A focus on system recovery from COVID-19 will be paramount. Smoking cessation must remain a core element of high-quality cancer care, so that patients achieve the best possible health benefits from their treatments.