Curbing the Illicit Market: Enhancing Firearm Regulations to Reduce Gun Violence

Almost all of the firearms that end up on the streets are first sold through legally appointed federally licensed firearm dealers (FFLs) following manufacture or import. Given the unique ease of access to firearms in the US, there is a growing sense of urgency to better understand how crime guns are acquired and from where they originate to support much stronger supply-side efforts to address gun violence. Prior research has focused extensively on the large "secondary market" for firearms, where guns are transferred between unlicensed persons or to those legally prohibited from buying a firearm. In contrast, the focus of this policy brief is on the "primary market," which includes the legal retail sale of firearms from federally licensed firearm dealers (FFLs) to private consumers

Agreement of two physical behaviour monitors for characterising posture and stepping in children aged 6-12 years

All new physical behaviour measurement devices should be assessed for compatibility with previous devices. Agreement was assessed between the activPAL4TM and activPAL3TM physical behavior monitors within a laboratory and a multi-day free-living context. Healthy children aged 6-12 years performed standardised (sitting, standing, stepping) (12 min) and non-standardised (6 min) activities in a laboratory and a multi-day (median 3 days) free-living assessment whilst wearing both monitors. Agreement was assessed using Bland-Altman plots, sensitivity, and the positive predictive value (PPV). There were 15 children (7M/8F, 8.4 ± 1.8 years old) recruited. For the laboratory-based standardised activities, sitting time, stepping time, and fast walking/jogging step count were all within ±5% agreement. However, the activPAL4TM standing time was lower (-6.4%) and normal speed walking step count higher (+7.8%) than those of the activPAL3TM. For non-standardised activities, a higher step count was recorded by the activPAL4TM (+4.9%). The standardised activity sensitivity and PPV were all &gt;90%, but the non-standardised activity values were lower. For free-living agreement, the standing time was lower (-7.6%) and step count higher (all steps + 2.2%, steps with cadence &gt;100 step/min + 6.6%) for the activPAL4TM than the activPAL3TM. This study highlights differences in outcomes as determined by the activPAL4TM and activPAL3TM, which should be considered when comparing outcomes between studies.</p

The global burden of hospitalisation due to pneumonia caused by Staphylococcus aureus in the under-5 years children:A systematic review and meta-analysis

BACKGROUND: Pneumonia is a leading cause of childhood morbidity and mortality. This study aimed to estimate the global hospitalisation due to Staphylococcus aureus pneumonia in under-5 children. METHODS: We conducted a systematic review and meta-analysis of primary studies following the PRISMA-P guidelines. We searched Medline, Embase, Global Health, CINAHL, Global Index Medicus, Scopus, China National Knowledge Infrastructure, Wanfang, and CQvip. We included studies reporting data on Staphylococcus aureus pneumonia, confirmed by detection of the pathogen in sterile-site samples in under-5 hospitalised children, published in English or Chinese language and conducted between 1st January 1990 and 4th November 2021 and between 1st January 1990 and 30th September 2020, respectively. We excluded those testing upper respiratory tract samples and not reporting data on samples with other bacteria or absence of bacteria. We screened papers against pre-specified criteria, extracted data and assessed the bacteriological quality, and combined epidemiological and microbiological quality of studies using two self-designed checklists. Pooled proportions of hospitalisation episodes for Staphylococcus aureus pneumonia amongst all-cause pneumonia and the 95% confidence intervals were calculated using the random-effects model. The review protocol was registered on PROSPERO (CRD42021236606). FINDINGS: Of 26,218 studies identified, thirty-five studies enroling 20,708 hospitalised pneumonia episodes were included. Out of the total hospitalised pneumonia cases in this population, the pooled proportion of Staphylococcal pneumonia cases was 3% (95% CI 2% to 4%; I(2)=96%). amongst 12 studies with higher microbiological quality, the pooled estimate was 6% (95% CI 2% to 10%; I(2)= 98%). Based on the recent global estimates of hospitalised pneumonia in this age group, the 3% and 6% estimates represent 738 thousand and 1.48 million hospitalisations in 2019, respectively. Based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE), the overall quality of evidence was considered to be moderate. INTERPRETATION: Our findings are probably an underestimate because of the unknown and the likely limited sensitivity of current testing methods for Staphylococcal pneumonia diagnosis and widespread reported use of antibiotics before recruitment (in 46% of cases). Staphylococcus aureus is an important cause of hospitalisation for pneumonia in young children globally. FUNDING: Bill and Melinda Gates Foundation (OPP 1,172,551) through a prime award to John Hopkins University

Lamb Wave Propagation in Thermally Damaged Composites

The use of composites in primary and secondary structures of aerospace vehicles is important for increased performance with little weight penalty. Determining the response to thermal damage is necessary for a complete understanding of the total use environment of these materials. The objective of the research presented here is to provide a method of quantifying the amount of thermal damage in composite materials. Components which have non-visible damage, but have degraded performance on the order of several percent, are of interest. At this level of damage the safety margin designed into the structure may be compromised

Neurofibromin Deficient Myeloid Cells are Critical Mediators of Aneurysm Formation In Vivo

Background Neurofibromatosis Type 1 (NF1) is a genetic disorder resulting from mutations in the NF1 tumor suppressor gene. Neurofibromin, the protein product of NF1, functions as a negative regulator of Ras activity in circulating hematopoietic and vascular wall cells, which are critical for maintaining vessel wall homeostasis. NF1 patients have evidence of chronic inflammation resulting in development of premature cardiovascular disease, including arterial aneurysms, which may manifest as sudden death. However, the molecular pathogenesis of NF1 aneurysm formation is unknown. Method and Results Utilizing an angiotensin II-induced aneurysm model, we demonstrate that heterozygous inactivation of Nf1 (Nf1+/−) enhanced aneurysm formation with myeloid cell infiltration and increased oxidative stress in the vessel wall. Using lineage-restricted transgenic mice, we show loss of a single Nf1 allele in myeloid cells is sufficient to recapitulate the Nf1+/− aneurysm phenotype in vivo. Finally, oral administration of simvastatin or the antioxidant apocynin, reduced aneurysm formation in Nf1+/− mice. Conclusion These data provide genetic and pharmacologic evidence that Nf1+/− myeloid cells are the cellular triggers for aneurysm formation in a novel model of NF1 vasculopathy and provide a potential therapeutic target

British Society of Gastroenterology guidance for management of inflammatory bowel disease during the COVID-19 pandemic.

The COVID-19 pandemic is putting unprecedented pressures on healthcare systems globally. Early insights have been made possible by rapid sharing of data from China and Italy. In the UK, we have rapidly mobilised inflammatory bowel disease (IBD) centres in order that preparations can be made to protect our patients and the clinical services they rely on. This is a novel coronavirus; much is unknown as to how it will affect people with IBD. We also lack information about the impact of different immunosuppressive medications. To address this uncertainty, the British Society of Gastroenterology (BSG) COVID-19 IBD Working Group has used the best available data and expert opinion to generate a risk grid that groups patients into highest, moderate and lowest risk categories. This grid allows patients to be instructed to follow the UK government's advice for shielding, stringent and standard advice regarding social distancing, respectively. Further considerations are given to service provision, medical and surgical therapy, endoscopy, imaging and clinical trials

Interactive Computer Technology for Planning and Policy Modeling

This paper speculates on the potential impacts of our increasing access to and use of computer technology and communication, especially with respect to planning and policy making. The focus of the discussion is on the interaction between the users of this expanding technology and the technology itself. Those involved in its development, whether it be the hardware or software of this technology, are in a position to make substantial contributions toward a more effective use of the models and their data bases by planners and policy analysts. Specific features of the technology and of environmental planning and policy-making processes are examined to identify where and how interactive computer-based models and associated hardware can best serve individuals, their organizations or institutions. Finally, the necessary conditions for the successful implementation of such tools and methods are identified

A propensity score-matched, real-world comparison of ustekinumab vs vedolizumab as a second-line treatment for Crohn's disease. The Cross Pennine study II

BackgroundThe optimal choice of biological agents after failure of anti-tumour-necrosis-factor-(TNF)α agent in Crohn's disease (CD) is yet to be defined.AimsTo assess the effectiveness and safety of ustekinumab compared to vedolizumab as second-line treatment in CD patients who failed anti-TNFα therapy.MethodsRetrospective analysis of clinical response and remission at 14 and 52 weeks to ustekinumab by physician global assessment (PGA). A propensity score-matched analysis with a cohort treated with vedolizumab was performed.ResultsOf 282 patients (mean age 40 ± 15, F:M ratio 1.7:1) treated with ustekinumab, clinical response or remission was reached by 200/282 patients (70.9%) at 14 weeks, and 162/259 patients (62.5%) at 52 weeks. Overall, 74 adverse events occurred, of which 26 were labelled as serious (8.3 per 100 person-year). After exclusion of patients without prior anti-TNFα exposure and patients previously exposed to vedolizumab or ustekinumab, we analysed 275/282 patients (97.5%) on ustekinumab and 118/135 patients (87.4%) on vedolizumab. Propensity score analysis revealed that at 14 weeks, patients treated with ustekinumab were 38% (95% CI 25%-50%; P ConclusionsUstekinumab was effective and well tolerated in this real-world cohort. While ustekinumab proved more effective at 14-weeks, we found no statistically significant differences at 52 weeks compared to vedolizumab

Predicted effects of the introduction of long-acting injectable cabotegravir pre-exposure prophylaxis in sub-Saharan Africa: a modelling study.

BACKGROUND: Long-acting injectable cabotegravir pre-exposure prophylaxis (PrEP) is recommended by WHO as an additional option for HIV prevention in sub-Saharan Africa, but there is concern that its introduction could lead to an increase in integrase-inhibitor resistance undermining treatment programmes that rely on dolutegravir. We aimed to project the health benefits and risks of cabotegravir-PrEP introduction in settings in sub-Saharan Africa. METHODS: With HIV Synthesis, an individual-based HIV model, we simulated 1000 setting-scenarios reflecting both variability and uncertainty about HIV epidemics in sub-Saharan Africa and compared outcomes for each with and without cabotegravir-PrEP introduction. PrEP use is assumed to be risk-informed and to be used only in 3-month periods (the time step for the model) when having condomless sex. We consider three groups at risk of integrase-inhibitor resistance emergence: people who start cabotegravir-PrEP after (unknowingly) being infected with HIV, those who seroconvert while on PrEP, and those with HIV who have residual cabotegravir drugs concentrations during the early tail period after recently stopping PrEP. We projected the outcomes of policies of cabotegravir-PrEP introduction and of no introduction in 2022 across 50 years. In 50% of setting-scenarios we considered that more sensitive nucleic-acid-based HIV diagnostic testing (NAT), rather than regular antibody-based HIV rapid testing, might be used to reduce resistance risk. For cost-effectiveness analysis we assumed in our base case a cost of cabotegravir-PrEP drug to be similar to oral PrEP, resulting in a total annual cost of USD$144 per year ($114 per year and $264 per year considered in sensitivity analyses), a cost-effectiveness threshold of$500 per disability-adjusted life years averted, and a discount rate of 3% per year. FINDINGS: Reflecting our assumptions on the appeal of cabotegravir-PrEP, its introduction is predicted to lead to a substantial increase in PrEP use with approximately 2·6% of the adult population (and 46% of those with a current indication for PrEP) receiving PrEP compared with 1·5% (28%) without cabotegravir-PrEP introduction across 20 years. As a result, HIV incidence is expected to be lower by 29% (90% range across setting-scenarios 6-52%) across the same period compared with no introduction of cabotegravir-PrEP. In people initiating antiretroviral therapy, the proportion with integrase-inhibitor resistance after 20 years is projected to be 1·7% (0-6·4%) without cabotegravir-PrEP introduction but 13·1% (4·1-30·9%) with. Cabotegravir-PrEP introduction is predicted to lower the proportion of all people on antiretroviral therapy with viral loads less than 1000 copies per mL by 0·9% (-2·5% to 0·3%) at 20 years. For an adult population of 10 million an overall decrease in number of AIDS deaths of about 4540 per year (-13 000 to -300) across 50 years is predicted, with little discernible benefit with NAT when compared with standard antibody-based rapid testing. AIDS deaths are predicted to be averted with cabotegravir-PrEP introduction in 99% of setting-scenarios. Across the 50-year time horizon, overall HIV programme costs are predicted to be similar regardless of whether cabotegravir-PrEP is introduced (total mean discounted annual HIV programme costs per year across 50 years is $151·3 million vs$150·7 million), assuming the use of standard antibody testing. With antibody-based rapid HIV testing, the introduction of cabotegravir-PrEP is predicted to be cost-effective under an assumed threshold of $500 per disability-adjusted life year averted in 82$144 per year, in 52% at $264, and in 87$114. INTERPRETATION: Despite leading to increases in integrase-inhibitor drug resistance, cabotegravir-PrEP introduction is likely to reduce AIDS deaths in addition to HIV incidence. Long-acting cabotegravir-PrEP is predicted to be cost-effective if delivered at similar cost to oral PrEP with antibody-based rapid HIV testing. FUNDING: Bill & Melinda Gates Foundation, National Institute of Allergy and Infectious Diseases of the National Institutes of Health