Strengthening healthcare through family medicine training in The Gambia: The journey so far.

According to the World Health Organizations (WHO) family medicine forms the bedrock upon for accessible, affordable and equitable healthcare for any country. The need for family doctors is more acute for low income countries like The Gambia. More so that The Gambian health infrastructure is suboptimal and appropriate health personnel is low. This is worsened by brain drain leading to poor health indices. Despite these challenges and more, the department of Family Medicine was accredited for training in the Gambia with improved infrastructure (at the training centre), with 7 residents. Though there are still challenges there are also opportunities and strengths. There is therefore hope that the right personnel will be produced for an improved Gambian health system.

Thrombosis with thrombocytopenia syndrome (TTS) following adenovirus vector COVID-19 vaccination in Canada.

INTRODUCTION: Identifying and monitoring adverse events following vaccination contributed to the safety and effectiveness of COVID-19 mass vaccination campaigns. In March 2021, international reports emerged of an adverse event following vaccination with adenovirus vector COVID-19 vaccines (ChAdOx1-S [recombinant] and Ad26.COV2.S) of thrombosis with low platelet counts, referred to as thrombosis with thrombocytopenia syndrome (TTS). We described TTS reports in Canada following adenovirus vector COVID-19 vaccines and investigated whether the observed number of events were higher than expected. METHODS: Reports of TTS following receipt of ChAdOx1-S [recombinant] or Ad26.COV2.S meeting the Canadian case definition for TTS and diagnostic certainty levels 1-3 of the Brighton Collaboration case definition, submitted to the Canadian Adverse Events Following Immunization Surveillance System and Canada Vigilance Database between February 26, 2021 and October 31, 2022 were included. Demographics and characteristics of the TTS reports are described along with an analysis comparing the observed number of reports to the expected number. RESULTS: As of October 31, 2022, 56 reports of TTS following administration of ChAdOx1-S [recombinant] and no reports following Ad26.COV2.S vaccines were reported in Canada, of which 37 had functionally positive anti-PF4 antibodies. The median age was 56 years; males accounted for 54 % of reports. Five deaths were reported. The observed number of reports exceeded the expected for all ages and sexes combined, as well as for males aged 30-49 and 60-69 years, and females aged 40-59 years. CONCLUSION: Based on international surveillance data, Canada evaluated a statistical signal of TTS following adenovirus vector vaccines. The investigation of this signal demonstrated how post-market vaccine safety surveillance systems were successful in investigating rare adverse events during the rollout of COVID-19 vaccines in Canada. As adenovirus vector vaccines continue to be administered, characterization of the association between the vaccine and TTS informs immunization programs and policies.

Residual risk associations between initial hyperglycemia and adverse pregnancy outcomes in a large cohort including 6709 women with gestational diabetes.

AIMS: To estimate the residual risk associations between hyperglycemia and adverse pregnancy outcomes after glycemia-controlling intervention. METHODS: Among 41,067 Chinese women, those with gestational diabetes mellitus (GDM), according to the IADPSG criteria, received standard interventions to control glycemia. Risk associations of plasma glucose (PG) levels with excess newborn birth weight, primary cesarean section, and preterm delivery were estimated and compared with those in the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study, where hyperglycemia was left untreated. RESULTS: A total of 6,709 (16.3%) women developed GDM and thus received predominantly lifestyle interventions. The incidence of excess newborn birth weight, primary cesarean section, and preterm delivery was 6.1%, 19.1%, and 4.0%, respectively. Higher fasting and higher post-load PG levels during 75-g oral glucose tolerance test (OGTT) were statistically significantly associated with increased risks of excess newborn birth weight and pre-term delivery. Compared with the HAPO study, the association of fasting PG level with excess newborn birth weight showed similar strength and dose-response pattern, contrasting with considerably weakened associations for post-load PG levels that involved glycemic control. Contrary risk associations were seen across GDM subtypes compared with non-GDM, isolated fasting GDM was associated with increased, whereas isolated post-load GDM was associated with decreased, risks of excess newborn birth weight and primary cesarean section. Limiting the analysis to non-GDM women and GDM women with low HbA1c (<6.0%) ≥30 days after interventions overall attenuated the risk associations. CONCLUSIONS: Residual risk associations exist between hyperglycemia and adverse pregnancy outcomes despite seemingly appropriate glycemic control.

Low genetic confirmation rate in South Indian subjects with a clinical diagnosis of maturity-onset diabetes of the young (MODY) who underwent targeted next-generation sequencing for 13 genes.

PURPOSE: To screen for maturity-onset diabetes of the young (MODY) variants in subjects with an early age of onset and positive family history of diabetes mellitus. METHODS: 60 subjects with onset of diabetes between 3 and 30 years of age and parental history (onset < 35 years) of diabetes were recruited after excluding autoimmune, pancreatic and syndromic forms of diabetes. Detailed pedigree chart and clinical data were recorded. MODY genetic testing (MODY 1-13) was performed and variant classification was done adhering to the ACMG guidelines. RESULTS: Baseline characteristics of subjects were as follows: mean age of onset of diabetes 19.9 ± 7 years, mean duration of diabetes 6.3 ± 6.8 years, BMI 23.3 ± 3 kg/m2 and C-peptide 1.56 ± 1.06 nmol/l. Four out of sixty (6.6%) were positive for variants classifiable as pathogenic/likely pathogenic: one patient with HNF4Ac.691C > T, (p.Arg231Trp), two with HNF 1A c.746C > A(p.Ser249Ter) and c.1340C > T(p.Pro447Leu), and one with ABCC8 c.4544C > T (p.Thr1515Met). MODY 1 and MODY 3 variants were documented in the paediatric age group (< 18 years). CONCLUSION: A genetic diagnosis of MODY could be confirmed in only 6.6% (4/60) of patients clinically classifiable as MODY. This is less than that reported in clinically diagnosed MODY subjects of European descent. Newly published population data and more stringent criteria for assessment of pathogenicity and younger age of onset of type 2 diabetes in Indians could have contributed to the lower genetic confirmation rate. Apart from variants in the classical genes (HNF1A, HNF4A), a likely pathogenic variant in a non-classical gene (ABCC8) was noted in this study.

Historical Origins for the Overestimation of Mammographic Sensitivity.

The sensitivity of screening mammography for the early detection of breast cancer has improved over the years due to advances in technology. However, guidelines for screening mammography are often based on the mortality reductions demonstrated in the historic trials, where sensitivity with the first-generation mammography was relatively low. With attempts to establish risk:benefit ratios for population screening, it is important to understand the wide range of sensitivities that have been reported for mammography.  Original calculations for mammographic sensitivity were often based on studies that included palpable tumors, thus generating inflated numbers not fully applicable to non-palpable tumors. If restricted to asymptomatic screening, sensitivity calculations were often based on the inverse of interval cancers, a relatively inaccurate method since breast cancers missed on mammography can remain undetected clinically for several years. It was not until multi-modality imaging was developed, primarily ultrasound and MRI, where sensitivity determinations could be made in real time by cross-checking outcomes with each modality. From this, it became apparent that there was a strong correlation between breast density levels and sensitivity levels, such that a single number to denote mammographic sensitivity was disingenuous. The increasing awareness that mortality reductions in the historic trials were achieved with a low sensitivity tool has prompted great interest in additional technologic improvements in mammography, as well as multi-modality imaging approaches for women with high density and/or high risk. In order to appreciate the potential benefit of these new approaches, it is helpful to understand the historical basis behind overestimating the sensitivity of screening mammography.

Search for Displaced Leptons in sqrt[s]=13 TeV pp Collisions with the ATLAS Detector.

A search for charged leptons with large impact parameters using 139 fb^{-1} of sqrt[s]=13 TeV pp collision data from the ATLAS detector at the LHC is presented, addressing a long-standing gap in coverage of possible new physics signatures. Results are consistent with the background prediction. This search provides unique sensitivity to long-lived scalar supersymmetric lepton partners (sleptons). For lifetimes of 0.1 ns, selectron, smuon, and stau masses up to 720, 680, and 340 GeV, respectively, are excluded at 95% confidence level, drastically improving on the previous best limits from LEP.

Feasibility of Breast MRI as the Primary Imaging Modality in a Large Asian Cohort.

Purpose Contrast-enhanced MRI has repeatedly demonstrated significantly enhanced sensitivity compared to mammography and ultrasound in breast cancer detection. The purpose of this study was to evaluate the feasibility and outcomes of using breast MRI as the initial imaging study for screening and diagnosis.  Materials and methods In this retrospective review of a cohort of 10,374 breast MRI scans in 7967 patients in Taitung County, Taiwan, a total of 5619 participants met inclusion criteria and were included in our analysis. We reviewed all biopsies that were performed subsequent to MRI studies in women (screening vs. diagnostic). The primary outcomes were false-positive (FP) biopsy rates and positive predictive value (PPV) of MRI - parameters that have historically been associated with performance that restricts more widespread use of MRI. False-positive rate based on benign biopsies (FPR-3) and the positive predictive value (PPV-3) were calculated. Results Without complementary imaging or follow-up to identify false negatives, the study of performance characteristics was limited to false positives and PPV. There were 351 benign biopsies generated by MRI out of the cohort of 5555 participants (5619 minus the malignant biopsies), generating a false-positive rate of 6.3%. Sixty-four patients out of 415 biopsies were malignant, generating a PPV-3 of 15.4%. Conclusion In this Asian cohort, utilizing breast MRI as the initial study for screening and/or diagnosis appears to be limited more by practical considerations such as cost and patient flow efficiency than by feasibility based on performance characteristics. With well-established superior sensitivity, coupled with improved interpretive skills and techniques that allow for low false-positive rates, MRI should be further studied for its role as the primary imaging modality in breast screening and diagnosis.

Knowledge, Attitude and Practice on Covid-19 among Clinical Healthcare Workers in Bingham University Teaching Hospital (BHUTH) Jos, Plateau State, Nigeria.

BACKGROUND: The ongoing Covid-19 pandemic is now a global health emergency with significant morbidity and mortality among different populations of the world. Healthcare professionals are the people in the front line of situations like this. Their perspectives on the pandemic is critical to their safety and the outcomes in patients they manage. The aim of this study is to assess the knowledge, attitude and practice regarding COVID-19 among clinical healthcare professionals in Bingham University Teaching Hospital (BHUTH) Jos. MATERIALS AND METHODS: A total of 138 clinical health workers from BHUTH completed a questionnaire- based study on the knowledge, attitude and practice on COVID-19 from the April 1st to 30th May 2020. Consecutive sampling method was used for data collection and the distribution of responses was presented as frequencies and percentages. Analysis of Variance (ANOVA) test was used to investigate the level of association among variables at the significance level of p<0.05. RESULTS: The highest mean of correct responses for knowledge were from doctors, pharmacists and nurses with 19.1±2.35, 19.4±1.52 and 18.9±1.73 respectively. The lowest mean was from pharmacist assistant and nurse aids with 17.1±1.81. The difference was statistically significant with Anaysis of Variance (F) of 5.75 and p value of 0.001. The attitude and practice mean were good between the different clinical cadre; however, the difference was not significant. CONCLUSION: There is good knowledge, attitude and practice among the doctors and pharmacists, nurses, nurse assistants and pharmacist assistants. The doctors and pharmacist had better scores. There is the need for regular training and update.

CONTEXTE: La pandémie de Covid-19 en cours est maintenant une urgence sanitaire mondiale avec une morbidité et une mortalité importantes parmi les différentes populations du monde. Les professionnels de la santé sont les personnes en première ligne dans des situations comme celle-ci. Leurs points de vue sur la pandémie sont essentiels à leur sécurité et aux résultats chez les patients qu'ils gèrent. Le but de cette étude est d'évaluer les connaissances, l'attitude et la pratique concernant le COVID-19 parmi les professionnels de la santé cliniques du Bingham University Teaching Hospital (BHUTH) Jos. MATÉRIAUX ET MÉTHODES: Un total de 138 agents de santé cliniques du BHUTH ont terminé une étude basée sur un questionnaire sur les connaissances, l'attitude et la pratique du COVID-19 du 1er avril au 30 mai 2020. La méthode d'échantillonnage consécutif a été utilisée pour la collecte des données et la distribution des réponses a été présentée sous forme de fréquences et de pourcentages. Le test d'analyse de variance (ANOVA) a été utilisé pour étudier le niveau d'association entre les variables au niveau de signification de p <0,05. RÉSULTATS: La moyenne la plus élevée de réponses correctes pour les connaissances était celle des médecins, des pharmaciens et des infirmières avec respectivement 19,1 ± 2,35, 19,4 ± 1,52 et 18,9 ± 1,73. La moyenne la plus faible était celle des assistants pharmaciens et des infirmières auxiliaires avec 17,1 ± 1,81. La différence était statistiquement significative avec F de 5,75 et p de 0,001. L'attitude et la pratique moyenne étaient bonnes entre les différents cadres cliniques; cependant, la différence n'était pas significative. CONCLUSION: Il existe de bonnes connaissances, une bonne attitude et une bonne pratique parmi les médecins et pharmaciens, infirmières, infirmières auxiliaires et pharmaciens assistants. Les médecins et le pharmacien avaient de meilleurs scores. Une formation et une mise à jour régulières sont nécessaires. MOTS CLÉS: COVID-19, connaissances, attitude, pratique, travailleurs de la santé, Nigéria.

Longitudinal Flow Decorrelations in Xe+Xe Collisions at sqrt[s_{NN}]=5.44 TeV with the ATLAS Detector.

The first measurement of longitudinal decorrelations of harmonic flow amplitudes v_{n} for n=2-4 in Xe+Xe collisions at sqrt[s_{NN}]=5.44 TeV is obtained using 3 µb^{-1} of data with the ATLAS detector at the LHC. The decorrelation signal for v_{3} and v_{4} is found to be nearly independent of collision centrality and transverse momentum (p_{T}) requirements on final-state particles, but for v_{2} a strong centrality and p_{T} dependence is seen. When compared with the results from Pb+Pb collisions at sqrt[s_{NN}]=5.02 TeV, the longitudinal decorrelation signal in midcentral Xe+Xe collisions is found to be larger for v_{2}, but smaller for v_{3}. Current hydrodynamic models reproduce the ratios of the v_{n} measured in Xe+Xe collisions to those in Pb+Pb collisions but fail to describe the magnitudes and trends of the ratios of longitudinal flow decorrelations between Xe+Xe and Pb+Pb. The results on the system-size dependence provide new insights and an important lever arm to separate effects of the longitudinal structure of the initial state from other early and late time effects in heavy-ion collisions.

Search for Dark Matter Produced in Association with a Dark Higgs Boson Decaying into W

Several extensions of the Standard Model predict the production of dark matter particles at the LHC. An uncharted signature of dark matter particles produced in association with VV=W^{±}W^{∓} or ZZ pairs from a decay of a dark Higgs boson s is searched for using 139 fb^{-1} of pp collisions recorded by the ATLAS detector at a center-of-mass energy of 13 TeV. The s→V(qq[over ¯])V(qq[over ¯]) decays are reconstructed with a novel technique aimed at resolving the dense topology from boosted VV pairs using jets in the calorimeter and tracking information. Dark Higgs scenarios with m_{s}>160 GeV are excluded.

Medium-Induced Modification of Z-Tagged Charged Particle Yields in Pb+Pb Collisions at 5.02 TeV with the ATLAS Detector.

The yield of charged particles opposite to a Z boson with large transverse momentum (p_{T}) is measured in 260 pb^{-1} of pp and 1.7 nb^{-1} of Pb+Pb collision data at 5.02 TeV per nucleon pair recorded with the ATLAS detector at the Large Hadron Collider. The Z boson tag is used to select hard-scattered partons with specific kinematics, and to observe how their showers are modified as they propagate through the quark-gluon plasma created in Pb+Pb collisions. Compared with pp collisions, charged-particle yields in Pb+Pb collisions show significant modifications as a function of charged-particle p_{T} in a way that depends on event centrality and Z boson p_{T}. The data are compared with a variety of theoretical calculations and provide new information about the medium-induced energy loss of partons in a p_{T} regime difficult to measure through other channels.

Search for Higgs Boson Decays into a Z Boson and a Light Hadronically Decaying Resonance Using 13 TeV pp Collision Data from the ATLAS Detector.

A search for Higgs boson decays into a Z boson and a light resonance in two-lepton plus jet events is performed, using a pp collision dataset with an integrated luminosity of 139 fb^{-1} collected at sqrt[s]=13 TeV by the ATLAS experiment at the CERN LHC. The resonance considered is a light boson with a mass below 4 GeV from a possible extended scalar sector or a charmonium state. Multivariate discriminants are used for the event selection and for evaluating the mass of the light resonance. No excess of events above the expected background is found. Observed (expected) 95% confidence-level upper limits are set on the Higgs boson production cross section times branching fraction to a Z boson and the signal resonance, with values in the range 17-340 pb (16_{-5}^{+6}-320_{-90}^{+130} pb) for the different light spin-0 boson mass and branching fraction hypotheses, and with values of 110 and 100 pb (100_{-30}^{+40} and 100_{-30}^{+40} pb) for the η_{c} and J/ψ hypotheses, respectively.

Methane Emissions in a Chemistry-Climate Model: Feedbacks and Climate Response.

Understanding the past, present, and future evolution of methane remains a grand challenge. Here we have used a hierarchy of models, ranging from simple box models to a chemistry-climate model (CCM), UM-UKCA, to assess the contemporary and possible future atmospheric methane burden. We assess two emission data sets for the year 2000 deployed in UM-UKCA against key observational constraints. We explore the impact of the treatment of model boundary conditions for methane and show that, depending on other factors, such as CO emissions, satisfactory agreement may be obtained with either of the CH4 emission data sets, highlighting the difficulty in unambiguous choice of model emissions in a coupled chemistry model with strong feedbacks. The feedbacks in the CH4-CO-OH system, and their uncertainties, play a critical role in the projection of possible futures. In a future driven by large increases in greenhouse gas forcing, increases in tropospheric temperature drive, an increase in water vapor, and, hence, [OH]. In the absence of methane emission changes this leads to a significant decrease in methane compared to the year 2000. However, adding a projected increase in methane emissions from the RCP8.5 scenario leads to a large increase in methane abundance. This is modified by changes to CO and NOx emissions. Clearly, future levels of methane are uncertain and depend critically on climate change and on the future emission pathways of methane and ozone precursors. We highlight that further work is needed to understand the coupled CH4-CO-OH system in order to understand better future methane evolution.

Minimal Climate Impacts From Short-Lived Climate Forcers Following Emission Reductions Related to the COVID-19 Pandemic.

We present an assessment of the impacts on atmospheric composition and radiative forcing of short-lived pollutants following a worldwide decrease in anthropogenic activity and emissions comparable to what has occurred in response to the COVID-19 pandemic, using the global composition-climate model United Kingdom Chemistry and Aerosols Model (UKCA). Emission changes reduce tropospheric hydroxyl radical and ozone burdens, increasing methane lifetime. Reduced SO2 emissions and oxidizing capacity lead to a decrease in sulfate aerosol and increase in aerosol size, with accompanying reductions to cloud droplet concentration. However, large reductions in black carbon emissions increase aerosol albedo. Overall, the changes in ozone and aerosol direct effects (neglecting aerosol-cloud interactions which were statistically insignificant but whose response warrants future investigation) yield a radiative forcing of -33 to -78 mWm-2. Upon cessation of emission reductions, the short-lived climate forcers rapidly return to pre-COVID levels; meaning, these changes are unlikely to have lasting impacts on climate assuming emissions return to pre-intervention levels.

Dijet Resonance Search with Weak Supervision Using sqrt[s]=13 TeV pp Collisions in the ATLAS Detector.

This Letter describes a search for narrowly resonant new physics using a machine-learning anomaly detection procedure that does not rely on signal simulations for developing the analysis selection. Weakly supervised learning is used to train classifiers directly on data to enhance potential signals. The targeted topology is dijet events and the features used for machine learning are the masses of the two jets. The resulting analysis is essentially a three-dimensional search A→BC, for m_{A}∼O(TeV), m_{B},m_{C}∼O(100 GeV) and B, C are reconstructed as large-radius jets, without paying a penalty associated with a large trials factor in the scan of the masses of the two jets. The full run 2 sqrt[s]=13 TeV pp collision dataset of 139 fb^{-1} recorded by the ATLAS detector at the Large Hadron Collider is used for the search. There is no significant evidence of a localized excess in the dijet invariant mass spectrum between 1.8 and 8.2 TeV. Cross-section limits for narrow-width A, B, and C particles vary with m_{A}, m_{B}, and m_{C}. For example, when m_{A}=3 TeV and m_{B}≳200 GeV, a production cross section between 1 and 5 fb is excluded at 95% confidence level, depending on m_{C}. For certain masses, these limits are up to 10 times more sensitive than those obtained by the inclusive dijet search. These results are complementary to the dedicated searches for the case that B and C are standard model bosons.

Reconciling the climate and ozone response to the 1257 CE Mount Samalas eruption.

The 1257 CE eruption of Mount Samalas (Indonesia) is the source of the largest stratospheric injection of volcanic gases in the Common Era. Sulfur dioxide emissions produced sulfate aerosols that cooled Earth's climate with a range of impacts on society. The coemission of halogenated species has also been speculated to have led to wide-scale ozone depletion. Here we present simulations from HadGEM3-ES, a fully coupled Earth system model, with interactive atmospheric chemistry and a microphysical treatment of sulfate aerosol, used to assess the chemical and climate impacts from the injection of sulfur and halogen species into the stratosphere as a result of the Mt. Samalas eruption. While our model simulations support a surface air temperature response to the eruption of the order of -1°C, performing well against multiple reconstructions of surface temperature from tree-ring records, we find little evidence to support significant injections of halogens into the stratosphere. Including modest fractions of the halogen emissions reported from Mt. Samalas leads to significant impacts on the composition of the atmosphere and on surface temperature. As little as 20% of the halogen inventory from Mt. Samalas reaching the stratosphere would result in catastrophic ozone depletion, extending the surface cooling caused by the eruption. However, based on available proxy records of surface temperature changes, our model results support only very minor fractions (1%) of the halogen inventory reaching the stratosphere and suggest that further constraints are needed to fully resolve the issue.

CP Properties of Higgs Boson Interactions with Top Quarks in the tt[over ¯]H and tH Processes Using H→γγ with the ATLAS Detector.

A study of the charge conjugation and parity (CP) properties of the interaction between the Higgs boson and top quarks is presented. Higgs bosons are identified via the diphoton decay channel (H→γγ), and their production in association with a top quark pair (tt[over ¯]H) or single top quark (tH) is studied. The analysis uses 139 fb^{-1} of proton-proton collision data recorded at a center-of-mass energy of sqrt[s]=13 TeV with the ATLAS detector at the Large Hadron Collider. Assuming a CP-even coupling, the tt[over ¯]H process is observed with a significance of 5.2 standard deviations. The measured cross section times H→γγ branching ratio is 1.64_{-0.36}^{+0.38}(stat)_{-0.14}^{+0.17}(sys) fb, and the measured rate for tt[over ¯]H is 1.43_{-0.31}^{+0.33}(stat)_{-0.15}^{+0.21}(sys) times the Standard Model expectation. The tH production process is not observed and an upper limit on its rate of 12 times the Standard Model expectation is set. A CP-mixing angle greater (less) than 43 (-43)° is excluded at 95% confidence level.