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Principles of Medicine in Africa combines clinical medicine with a rich understanding of the major environmental and cultural influences on health and disease, providing comprehensive guidance for anyone intending to practise medicine in Africa. Presenting disease in the context of family and culture, the effects of inequality and problems of limited resources are addressed. The authors have a wealth of experience in front line healthcare in Africa and provide practical, evidence-based management guidelines for all the common and less common conditions likely to be encountered. This fifth edition has been thoroughly updated to incorporate the latest research findings and management guidelines and there has been much greater involvement of African physicians in the writing and editorial process. The chapters on cancer and non-communicable diseases have been expanded and new chapters have been added on digital health, critical care in a resource-limited setting, antimicrobial resistance, COVID-19 and other emerging infectious diseases.
We present the first nonlinear results on the problem of non-rotating thermal convection in an internally heated full sphere. A nonlinear stability analysis by the energy method yields that, at least for no-slip boundary conditions, the critical Rayleigh numbers for linear stability and nonlinear stability coincide. We then explore different ranges of the parameter regime using direct numerical simulations. We first report on the system behaviour for a fixed Prandtl number of unity and both stress-free and no-slip boundary conditions up to very high forcing, reaching Rayleigh number $Ra=2\times 10^{12}$, approximately 250 million times the critical value ($Ra_c$) for the onset of convection under no-slip conditions. For both boundary conditions, we observe a scaling for the advective heat transfer measured by the Nusselt number $Nu$ close to $Nu \sim Ra^{1/4}$. This is consistent with a scaling prediction that we formulate analogously to the classical scaling in Rayleigh–Bénard convection. We then investigate the Prandtl number dependence at low to intermediate forcing for stress-free boundary conditions in the ranges $0.1 \leq Pr \leq 30$ and $Ra_c=3091\leq Ra \leq 3\times 10^5 \approx 100Ra_c$. We find five distinct dynamical regimes depending on the Prandtl number, describe each regime individually and issue heuristic interpretations of the system behaviour where possible.
In 2003, Ozsváth, Szabó and Rasmussen introduced the $\tau $ invariant for knots, and in 2011, Sarkar [‘Grid diagrams and the Ozsváth–Szabó tau-invariant’, Math. Res. Lett.18(6) (2011), 1239–1257] published a computational shortcut for the $\tau $ invariant of knots that can be represented by diagonal grid diagrams. Previously, the only knots known to have diagonal grid diagram representations were torus knots. We prove that all such knots are positive knots and we produce an example of a knot with a diagonal grid diagram representation which is not a torus knot.
To describe the real-world clinical impact of a commercially available plasma cell-free DNA metagenomic next-generation sequencing assay, the Karius test (KT).
Methods:
We retrospectively evaluated the clinical impact of KT by clinical panel adjudication. Descriptive statistics were used to study associations of diagnostic indications, host characteristics, and KT-generated microbiologic patterns with the clinical impact of KT. Multivariable logistic regression modeling was used to further characterize predictors of higher positive clinical impact.
Results:
We evaluated 1000 unique clinical cases of KT from 941 patients between January 1, 2017–August 31, 2023. The cohort included adult (70%) and pediatric (30%) patients. The overall clinical impact of KT was positive in 16%, negative in 2%, and no clinical impact in 82% of the cases. Among adult patients, multivariable logistic regression modeling showed that culture-negative endocarditis (OR 2.3; 95% CI, 1.11–4.53; P .022) and concern for fastidious/zoonotic/vector-borne pathogens (OR 2.1; 95% CI, 1.11–3.76; P .019) were associated with positive clinical impact of KT. Host immunocompromised status was not reliably associated with a positive clinical impact of KT (OR 1.03; 95% CI, 0.83–1.29; P .7806). No significant predictors of KT clinical impact were found in pediatric patients. Microbiologic result pattern was also a significant predictor of impact.
Conclusions:
Our study highlights that despite the positive clinical impact of KT in select situations, most testing results had no clinical impact. We also confirm diagnostic indications where KT may have the highest yield, thereby generating tools for diagnostic stewardship.
The interaction between national constitutions and transnational sources of law (foreign and international) has generated quite an active disagreement in the United States about what these bodies of law have to do with each other. This paper will explore these debates and the postures towards transnational law and its role in domestic constitutional adjudication which they express. It will identify three postures — of convergence, of resistance, and of engagement — that are manifest in the opinions of different justices of important high courts around the world, and will argue for a posture of ‘engagement’ at least in established constitutional systems like that of the United States.
Today is a time of retrogression in sustaining rights-protecting democracies, and of high levels of distrust in institutions. Of particular concern are threats to the institutions, including universities and the press, that help provide the information base for successful democracies. Attacks on universities, and university faculties, are rising. In Poland over the last four years, a world-renowned constitutional law theorist, Wojciech Sadurski, has been subject to civil and criminal prosecutions for defamation of the governing party. In Hungary, the Central European University (CEU) was ejected by the government, and had to partly relocate to Vienna, and other attacks on academic freedom followed. Faculty members in a number of countries have needed to relocate to other countries for their own safety. Governments attack what subjects can be taught – in Hungary bans on gender studies; in Poland, a government minister issued a call to ban gender studies and ‘LGBT ideology’. Attacks on academics and universities, through government restrictions and public or private violence, are not limited to Poland and Hungary, but are of concern in Brazil, India, Turkey and a range of other countries. Attacks on journalists are similarly rising. These developments are deeply concerning. The proliferation of ‘fake news’, doctored photos and false claims on social media has been widely documented. Constitutional democracy cannot long be sustained in an ‘age of lies’, where truth and knowledge no longer matter.
We show that if $\Gamma $ is a point group of $\mathbb {R}^{k+1}$ of order two for some $k\geq 2$ and $\mathcal {S}$ is a k-pseudomanifold which has a free automorphism of order two, then either $\mathcal {S}$ has a $\Gamma $-symmetric infinitesimally rigid realisation in ${\mathbb R}^{k+1}$ or $k=2$ and $\Gamma $ is a half-turn rotation group. This verifies a conjecture made by Klee, Nevo, Novik and Zheng for the case when $\Gamma $ is a point-inversion group. Our result implies that Stanley’s lower bound theorem for centrally symmetric polytopes extends to pseudomanifolds with a free simplicial automorphism of order 2, thus verifying (the inequality part of) another conjecture of Klee, Nevo, Novik and Zheng. Both results actually apply to a much larger class of simplicial complexes – namely, the circuits of the simplicial matroid. The proof of our rigidity result adapts earlier ideas of Fogelsanger to the setting of symmetric simplicial complexes.
Understanding the processes that allow phylogenetically related plant species coexist is important to understand the ecological and evolutionary processes that structure biological communities. In this study, we investigated how the species Erythroxylum simonis, Erythroxylum pauferrense and Erythroxylum citrifolium share ecological niche dimensions according to the abiotic characteristics of their environments of occurrence. To this end, in ten pre-established plots in an Atlantic Forest remnant in northeastern Brazil, we carried out a population survey of the three species and characterised their abiotic niche by measuring light availability, humidity and the physical–chemical properties of the soil. We used generalised linear models to test whether abiotic variables influence species abundance. Our results indicate that the three species coexist along the different environmental gradients, with some level of niche overlap. The species E. simonis is the best competitor, showing generalist behaviour and the highest abundance in all environmental gradients. We emphasise that the adult populations of the species have adapted to various environmental and ecological challenges. Thus, the results reported are influenced by their ability to perform well in terms of physiology, growth and survival in their early-life stages.
In June of 2024, Becton Dickinson experienced a blood culture bottle shortage for their BACTEC system, forcing health systems to reduce usage or risk exhausting their supply. Virginia Commonwealth University Health System (VCUHS) in Richmond, VA decided that it was necessary to implement austerity measures to preserve the blood culture bottle supply.
Setting:
VCUHS includes a main campus in Richmond, VA as well as two affiliate hospitals in South Hill, VA (Community Memorial Hospital (CMH)) and Tappahannock Hospital in Tappahannock, VA. It also includes a free-standing Emergency Department in New Kent, VA.
Patients:
Blood cultures from both pediatric and adult patients were included in this study.
Interventions:
VCUHS intervened to decrease blood culture utilization across the entire health system. Interventions included communication of blood culture guidance as well as an electronic health record order designed to guide providers and discourage wasteful ordering.
Results:
Post-implementation analyses showed that interventions reduced overall usage by 35.6% (P < .0001) and by greater than 40% in the Emergency Departments. The impact of these changes in utilization on positivity were analyzed, and it was found that the overall positivity rate increased post-intervention from 8.8% to 12.1% (P = .0115) and in the ED specifically from 10.2% to 19.5% (P < .0001).
Conclusions:
These findings strongly suggest that some basic stewardship interventions can significantly change blood culture practice in a manner that minimizes the impact on patient care.
Written by key names in the field, this book explores the impact of digitization and COVID-19 on justice in housing and special needs education. It analyses access to justice, offers recommendations for improvement and provides valuable insights into administrative justice from user perspectives.
Celiac disease (CD), an autoimmune disorder triggered by gluten, impacts about one percent of the population. Only one-third receive a diagnosis, leaving the majority unaware of their condition. Untreated CD can lead to gut lining damage, resulting in malnutrition, anemia, and osteoporosis. Our primary goal was to identify at-risk groups and assess the cost-effectiveness of active case finding in primary care.
Methods
Our methodology involved systematic reviews and meta-analyses focusing on the accuracy of CD risk factors (chronic conditions and symptoms) and diagnostic tests (serological and genetic). Prediction models, based on identified risk factors, were developed for identifying individuals who would benefit from CD testing in routine primary care. Additionally, an online survey gauged individuals’ preferences regarding diagnostic certainty before initiating a gluten-free diet. This information informed the development of economic models evaluating the cost-effectiveness of various active case finding strategies.
Results
Individuals with dermatitis herpetiformis, a family history of CD, migraine, anemia, type 1 diabetes, osteoporosis, or chronic liver disease showed one and a half to two times higher risk of having CD. IgA tTG, and EMA demonstrated good diagnostic accuracy. Genetic tests showed high sensitivity but low specificity. Survey results indicated substantial variation in preference for certainty from a blood test before initiating a gluten-free diet. Cost-effectiveness analyses showed that, in adults, IgA tTG at a one percent pre-test probability (equivalent to population screening) was the most cost effective. For non-population screening strategies, IgA EMA plus HLA was most cost effective. There was substantial uncertainty in economic model results.
Conclusions
While population-based screening with IgA tTG appears the most cost effective in adults, decisions for implementation should not solely rely on economic analyses. Future research should explore whether population-based CD screening aligns with UK National Screening Committee criteria and requires a long-term randomized controlled trial of screening strategies.
Emergency department (ED) visits for epilepsy are common, costly, and often clinically unnecessary. Configuration of care pathways (CPs) that could divert people away from ED offer an alternative. The aim was to measure patient and carer preferences for alternative CPs and to explore the feasibility of implementing the preferred CPs in the National Health Service (NHS) England with a wider group of stakeholders.
Methods
Formative work (provider survey, service-user interviews, knowledge exchange, and think-aloud piloting) informed a discrete choice experiment (DCE) with six attributes: access to care plan, conveyance, time, epilepsy specialist today, general practitioner (GP) notification, and epilepsy specialist follow-up. This was hosted online with random assignment to two of three scenarios (home, public, or atypical). Logistic regression generated preference weights that were used to calculate the utility of CPs. The highest ranked CPs plus a status quo were discussed at three online knowledge exchange workshops. The nominal group technique was used to ascertain stakeholder views on preference evidence and to seek group consensus on optimal feasible alternatives.
Results
A sample of 427 people with epilepsy and 167 friends or family completed the survey. People with epilepsy preferred paramedics to have access to care plan, non-conveyance, one to three hours, epilepsy specialists today, GP notification, and specialist follow-up within two to three weeks. Family and friends differed when considering atypical seizures, favoring conveyance to urgent treatment centers and shorter time. Optimal configuration of services from service users’ perspectives outranked current practice. Knowledge exchange (n=27 participants) identified the optimal CP as feasible but identified two scenarios for resource reallocation: care plan substitutes specialist advice today and times of strain on NHS resources.
Conclusions
Preferences differed to current practice but had minimal variation by seizure type or stakeholder. This study clearly identified optimal and feasible alternative CPs. The mixed-methods approach allowed for robust measurement of preferences, whilst knowledge exchange examined feasibility to enhance implementation of optimal alternative CPs in the future.
Economic evaluation using decision analytical models (DAMs) plays a limited role in shaping healthcare resource optimization and reimbursement decisions in the Middle East. This review aimed to systematically examine economic evaluation studies focusing on DAMs of medicines in the Middle East, defining methodological characteristics and appraising the quality of the identified models.
Methods
Six databases were searched (MEDLINE, Embase, EconLit, Web of Science, the Global Health Cost-Effectiveness Analysis Registry, and the Global Index Medicus) from 1998 to September 2023 to identify published DAMs of medicines in the Middle East. Studies meeting the inclusion criteria—full economic evaluations of medicines using a model-based method in the Middle East—were included. Data were extracted and tabulated to include study characteristics and methodological specifications. The results were analyzed narratively. The Philips checklist was used to assess the quality of the studies.
Results
Sixty-two DAM studies of medicines were identified from nine Middle Eastern countries, the majority of which (76%) were conducted in Iran, Turkey, and Saudi Arabia. The cost effectiveness of medications for non-communicable diseases was explored in 70 percent of the models. Cost-effectiveness thresholds based on gross domestic product were commonly used. International sources provided data on intervention effectiveness and health outcomes, while national sources were mainly used for the costs of resource use. Most models incorporated an assessment of parameter uncertainty, whereas other types of uncertainty were not explored. Studies from high-income countries were generally of higher quality than those from middle-income countries.
Conclusions
The number of published DAMs was low considering the available medicines and disease burden. Key aspects of high quality DAMs regarding model structure, input sources, and uncertainty assessment were not consistently fulfilled. Recommendations for future studies and policies included strengthening existing health economic capacities, establishing country-specific health technology assessment systems, and initiating collaborations to generate national cost and outcome data.
Technology is central in supporting older people with their daily tasks and independence at home. This project aimed to identify technologies that can be built into residential environments (e.g., appliances, fixtures, or fittings) to support older people in activities of daily living (ADL) through a horizon scan (HS) informed by public insights on unmet needs and priorities.
Methods
A survey of members of the public was conducted to prioritize outcomes included within an evidence and gap map (EGM) framework. The EGM aimed to illustrate the current landscape of technologies supporting ADL in residential settings (e.g., care homes) and innovation gaps. The EGM results were shared with end users in a workshop discussion on the current range of technologies aimed at supporting ADL in residential settings. This was facilitated using vignettes to elicit views on unmet needs and priorities for technology development. The workshop informed the scope of the HS to identify and prioritize emerging technologies that could address unmet needs.
Results
This project successfully embedded public involvement throughout to identify innovation gaps in technologies supporting ADL, unmet needs among end users, and potential solutions to these needs. The HS identified 190 technologies that were ready to market. All the technologies had potential to address identified unmet needs and could be built into the residential environment to support older people with ADL and to improve their quality of life, independence, and safety at home. Horizon scanning research can meaningfully involve stakeholders and take direction from their insights to enable voices less often heard to drive innovation in areas where it is needed.
Conclusions
Involving stakeholders in research using evidence synthesis and qualitative methods helps to gain a better understanding of gaps in innovation, the related unmet needs, and the technologies that might address these needs. Public involvement in the survey and workshop influenced the conduct and interpretation of the EGM, the scope of the HS, and the interpretation of the findings.
A general one-way analysis of variance components with unequal replication numbers is used to provide unbiased estimates of the true and error score variance of classical test theory. The inadequacy of the ANOVA theory is noted and the foundations for a Bayesian approach are detailed. The choice of prior distribution is discussed and a justification for the Tiao-Tan prior is found in the particular context of the “n-split” technique. The posterior distributions of reliability, error score variance, observed score variance and true score variance are presented with some extensions of the original work of Tiao and Tan. Special attention is given to simple approximations that are available in important cases and also to the problems that arise when the ANOVA estimate of true score variance is negative. Bayesian methods derived by Box and Tiao and by Lindley are studied numerically in relation to the problem of estimating true score. Each is found to be useful and the advantages and disadvantages of each are discussed and related to the classical test-theoretic methods. Finally, some general relationships between Bayesian inference and classical test theory are discussed.
Let ∑x be the (population) dispersion matrix, assumed well-estimated, of a set of non-homogeneous item scores. Finding the greatest lower bound for the reliability of the total of these scores is shown to be equivalent to minimizing the trace of ∑x by reducing the diagonal elements while keeping the matrix non-negative definite. Using this approach, Guttman's bounds are reviewed, a method is established to determine whether his λ4 (maximum split-half coefficient alpha) is the greatest lower bound in any instance, and three new bounds are discussed. A geometric representation, which sheds light on many of the bounds, is described.
In many applications, it is desirable to estimate binomial proportions in m groups where it is anticipated that these proportions are similar but not identical. Following a general approach due to Lindley, a Bayesian Model II aposteriori modal estimate is derived that estimates the inverse sine transform of each proportion by a weighted average of the inverse sine transform of the observed proportion in the individual group and the average of the estimated values. Comparison with a classical method due to Jackson spotlights some desirable features of Model II analyses. The simplicity of the present formulation makes it possible to study the behavior of the Bayesian Model II approach more closely than in more complex formulations. Also, it is possible to estimate the amount of gain afforded by the Model II analyses.
It is demonstrated that the squared multiple correlation of a variable with the remaining variables in a set of variables is a function of the communalities and the squared canonical correlations between the observed variables and common factors. This equation is shown to imply a strict inequality between the squared multiple correlation and communality.
Aspects of an entrenched constitution that were essential parts of founding compromises, and justified as necessary when a constitution was first adopted, may become less justifiable over time. Is this the case with respect to the structure of the United States Senate? The US Senate is hardwired in the Constitution to consist of an equal number of Senators from each state—the smallest of which currently has about 585,000 residents, and the largest of which has about 39.29 million. As this essay explains, over time, as population inequalities among states have grown larger, so too has the disproportionate voting power of smaller-population states in the national Senate. As a result of the ‘one-person, one-vote’ decisions of the 1960s that applied to both houses of state legislatures, each state legislature now is arguably more representative of its state population than the US Congress is of the US population. The ‘democratic deficit’ of the Senate, compared to state legislative bodies, also affects presidential (as compared to gubernatorial) elections. When founding compromises deeply entrenched in a constitution develop harder-to-justify consequences, should constitutional interpretation change responsively? Possible implications of the ‘democratic’ difference between the national and the state legislatures for US federalism doctrine are explored, especially with respect to the ‘pre-emption’ doctrine. Finally, the essay briefly considers the possibilities of federalism for addressing longer term issues of representation, polarisation and sustaining a single nation.