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Now in its fourth edition, this best-selling, highly praised text has been fully revised and updated with expanded sections on propensity analysis, sensitivity analysis, and emulation trials. As before, it focuses on easy-to follow explanations of complicated multivariable techniques including logistic regression, proportional hazards analysis, and Poisson regression. The perfect introduction for medical researchers, epidemiologists, public health practitioners, and health service researchers, this book describes how to preform and interpret multivariable analysis, using plain language rather than mathematical formulae. It takes advantage of the availability of user-friendly software that allow novices to conduct complex analysis without programming experience; ensuring that these analyses are set up and interpreted correctly. Numerous tables, graphs, and tips help to demystify the process of performing multivariable analysis. The text is illustrated with many up-to-date examples from the published literature that enable readers to model their analyses after well conducted research, increasing chances of top-tier publication.
Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.
Methods
T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).
Results
PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).
Conclusions
PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.
We determine the geometric monodromy groups attached to various families, both one-parameter and multi-parameter, of exponential sums over finite fields, or, more precisely, the geometric monodromy groups of the $\ell $-adic local systems on affine spaces in characteristic $p> 0$ whose trace functions are these exponential sums. The exponential sums here are much more general than we previously were able to consider. As a byproduct, we determine the number of irreducible components of maximal dimension in certain intersections of Fermat surfaces. We also show that in any family of such local systems, say parameterized by an affine space S, there is a dense open set of S over which the geometric monodromy group of the corresponding local system is a fixed known group.
The studies of Bonaventura Cavalieri’s indivisibles by Giusti, Andersen, Mancosu and others provide a comprehensive picture of Cavalieri’s mathematics, as well as of the mathematical objections to it as formulated by Paul Guldin and other critics. Issues that have been studied in less detail concern the theological underpinnings of the contemporary debate over indivisibles, its historical roots, the geopolitical situation at the time, and its relation to the ultimate suppression of Cavalieri’s religious order. We analyze sources from the seventeenth through twenty-first centuries to investigate this relationship.
Global challenges such as climate change demand transnational responses, including from legal clinics. Building on earlier community legal clinic and international human rights clinic models, transnational legal clinics combine the objectives of legal clinics with the framework of transnational law to work across domestic and international planes. This article focuses on a Canadian–Peruvian legal clinic collaboration to research and draft an amicus curiae brief for landmark climate litigation in Peru. While the global north–south axis of collaboration raises structural challenges, adopting a transnational approach unites participants around the principle of solidarity and decentres assumptions about expertise. A transnational approach also contributes to the progressive development of law, in this case by offering insights into remedies in climate litigation. Overall, we argue that transnational legal clinic collaboration can spur participants’ reflective learning and make substantive contributions to the growing number of climate cases.
Respiratory virus testing is routinely performed and ways to obtain specimens aside from a nasopharyngeal swab are needed for pandemic preparedness. The main objective is to validate a self-collected oral-nasal swab for the detection of Influenza and respiratory syncytial virus (RSV).
Design:
Diagnostic test validation of a self-collected oral nasal swab as compared to a provider-collected nasopharyngeal swab.
Setting:
Emergency Department at Michael Garron Hospital.
Participants:
Consecutive individuals who presented to the Emergency Department with a suspected viral upper respiratory tract infection were included if they self-collected an oral-nasal swab. Individuals testing positive for Influenza or RSV along with randomly selected participants who tested negative were eligible for inclusion.
Interventions:
All participants had the paired oral-nasal swab tested using a multiplex respiratory virus polymerase chain reaction for the three respiratory pathogens and compared to the nasopharyngeal swab.
Results:
48 individuals tested positive for Influenza, severe acute respiratory coronavirus virus 2 (SARS-CoV-2) or RSV along with 80 who tested negative. 110 were symptomatic with the median time from symptom onset to testing of 1 day (interquartile range 2–5 days). Using the clinical nasopharyngeal swab as the reference standard, the sensitivity was 0.75 (95% CI, 0.43–0.95) and specificity was 0.99 (95% CI, 0.93–1.00) for RSV, sensitivity is 0.67 (95% CI, 0.49–0.81) and specificity is 0.96 (95% CI, 0.89–0.99) for Influenza.
Conclusions:
Multiplex testing with a self-collected oral-nasal swab for Influenza and RSV is not an acceptable substitute for a healthcare provider collected nasopharyngeal swab primarily due to suboptimal Influenza test characteristics.
Machine learning has exhibited substantial success in the field of natural language processing (NLP). For example, large language models have empirically proven to be capable of producing text of high complexity and cohesion. However, at the same time, they are prone to inaccuracies and hallucinations. As these systems are increasingly integrated into real-world applications, ensuring their safety and reliability becomes a primary concern. There are safety critical contexts where such models must be robust to variability or attack and give guarantees over their output. Computer vision had pioneered the use of formal verification of neural networks for such scenarios and developed common verification standards and pipelines, leveraging precise formal reasoning about geometric properties of data manifolds. In contrast, NLP verification methods have only recently appeared in the literature. While presenting sophisticated algorithms in their own right, these papers have not yet crystallised into a common methodology. They are often light on the pragmatical issues of NLP verification, and the area remains fragmented. In this paper, we attempt to distil and evaluate general components of an NLP verification pipeline that emerges from the progress in the field to date. Our contributions are twofold. First, we propose a general methodology to analyse the effect of the embedding gap – a problem that refers to the discrepancy between verification of geometric subspaces, and the semantic meaning of sentences which the geometric subspaces are supposed to represent. We propose a number of practical NLP methods that can help to quantify the effects of the embedding gap. Second, we give a general method for training and verification of neural networks that leverages a more precise geometric estimation of semantic similarity of sentences in the embedding space and helps to overcome the effects of the embedding gap in practice.
Increasing numbers of Americans are affected by serious mental illness and severe substance use disorders. While funding has increased for the treatment of these conditions in recent years, increases in service needs have outstripped resources. Further, too often those living with these conditions are incarcerated, held for inordinate periods without treatment in emergency departments, and/or relegated to the streets as part of the burgeoning numbers of homeless in the United States. These conditions require innovative approaches to care that should include integrated medical care and community resources to decrease isolation and to improve the response to crises as they occur. There are numerous opportunities already in place that, used appropriately, can improve outcomes for some of our most vulnerable people and will improve community living for all. This perspective describes available resources that can better address the mental health and substance use crisis facing the American people.
Edited by
Dharti Patel, Mount Sinai West and Morningside Hospitals, New York,Sang J. Kim, Hospital for Special Surgery, New York,Himani V. Bhatt, Mount Sinai West and Morningside Hospitals, New York,Alopi M. Patel, Rutgers Robert Wood Johnson Medical School, New Jersey
This chapter covers respiratory physiology, including lung volumes and mechanics, ventilation and perfusion, compliance, diffusion, oxygen transport, carbon dioxide transport, effects of hypercarbia and hypoxemia, arterial blood gas interpretation, work of breathing, control of ventilation, non-respiratory functions of the lung, and the effects of perioperative smoking. The material is presented in a concise review format, with an emphasis on key words and concepts.
Edited by
Dharti Patel, Mount Sinai West and Morningside Hospitals, New York,Sang J. Kim, Hospital for Special Surgery, New York,Himani V. Bhatt, Mount Sinai West and Morningside Hospitals, New York,Alopi M. Patel, Rutgers Robert Wood Johnson Medical School, New Jersey
Lower respiratory tract disorders, which include pulmonary disorders like asthma and chronic obstructive pulmonary disease (COPD), are prevalent. This chapter discusses the pharmacology of some of the important classes of drugs used to treat these conditions. Bronchodilators relax smooth muscles and expand airways. Beta-2 agonists and anticholinergics are the two most commonly used bronchodilators used for this purpose. They are available in both short-acting and long-acting formulations. Short-acting (e.g. albuterol) are used as required for sudden episodes of breathlessness, while long-acting may be added if symptoms are not controlled or progress. Bronchodilators help to improve a patient’s overall quality of life through improved lung function, a decrease in symptoms, and improved exercise capacity. Corticosteroids, leukotriene modifiers, mast cell stabilizers, and Immunoglobulin E (IgE) blockers are classes of anti-inflammatory medications that have been shown to be effective treatments in controlling asthma symptoms and attacks. Research and experience have shown that a combination of these medications may be required. This can particularly be true for patients with intermediate and severe symptoms where a single medication has been inadequate in controlling/preventing recurrent symptoms.
The international order that the United States has for decades led and maintained is undergoing dramatic change. In this Essay, we explain that international law during this period was constituted with, and dependent on, U.S. power; that the two became (in odd-couple fashion) entwined together; and that, as the international order changes, the international legal system, its content and its architecture, will also inevitably change.
The impact of required durations of therapy for antibiotic orders at the time of order entry has not been reported. Requiring ordering clinicians to enter stop dates at the time of antibiotic order entry decreased DOT/1000 patient days for orders with empiric indication from 154 to 119 (–34.9 (–55.7 to –14)).
Poor diets and food insecurity during adolescence can have long-lasting effects, and Métis youth may be at higher risk. This study, as part of the Food and Nutrition Security for Manitoba Youth study, examines dietary intakes, food behaviours and health indicators of Métis compared with non-Métis youth.
Design:
This observational cross-sectional study involved a cohort of adolescents who completed a self-administered web-based survey on demographics, dietary intake (24-h recall), food behaviours, food security and select health indicators.
Setting:
Manitoba, Canada
Participants:
Participants included 1587 Manitoba grade nine students, with 135 (8·5 %) self-identifying as Métis, a distinct Indigenous nation living in Canada.
Results:
Median intake of sugar was significantly higher in Métis (89·2 g) compared with non-Métis (76·3 g) participants. Percent energy intake of saturated fat was also significantly higher in Métis (12·4 %) than non-Métis (11·6 %) participants. Median intakes of grain products and meat and alternatives servings were significantly lower among Métis than non-Métis (6·0 v. 7·0 and 1·8 v. 2·0, respectively) participants. Intake of other foods was significantly higher in Métis (4·0) than non-Métis (3·0). Significantly more Métis participants were food insecure (33·1 %) compared with non-Métis participants (19·1 %). Significantly more Métis participants ate family dinners and breakfast less often than non-Métis participants and had lower self-reported health. Significantly more Métis participants had a BMI classified as obese compared with non-Métis participants (12·6 % v. 7·1 %).
Conclusions:
The dietary intakes observed in this study, both among Métis and non-Métis youth, are concerning. Many have dietary patterns that put them at risk for developing health issues in the future.
For the purpose of reaching a decision about potentially defective administrative action into which he is conducting an investigation, the Ombudsman may wish to compel people to engage in various sorts of testimonial activity—the furnishing of information in writing, the production of documents, the answering of questions orally. This article examines the Ombudsman’s powers in that regard, pointing to matters which may give rise to difficulties in the exercise of such powers and suggesting a number of changes to the relevant provisions. Some of the matters discussed are relevant to the information-gathering powers of other Commonwealth agencies, for example, the Taxation Commissioner and the Trade Practices Commission. Not discussed in the article is the question of excuses which can be made to avoid complying with a valid request once made, a subject which deserves its own treatment separately.
This qualitative study aimed to understand facilitators and barriers to implementation of interventions to improve guideline-concordant antibiotic duration prescribing for pediatric acute otitis media (AOM).
Design:
Clinicians and clinic administrators participated in semi-structured qualitative interviews, and parents of children 2 years of age or older with a recent diagnosis of AOM participated in focus groups. The Practical Robust Implementation and Sustainability Model (PRISM) guided the study. Interviews were analyzed using the Rapid Assessment Process.
Setting:
Denver Health and Hospital Authority (Denver, CO) led the study. Recruitment occurred at Vanderbilt University Medical Center (Nashville, TN) and Washington University in St. Louis Medical Center (St. Louis, MO).
Participants:
Purposeful sampling was used to recruit clinicians and administrators for qualitative interviews. Convenience sampling was used to recruit parents for focus groups.
Results:
Thirty-one participants (15 clinicians, 4 administrators, and 12 parents) engaged in interviews and focus groups. Factors influencing antibiotic prescribing included patient history, years of practice, familiarity with the patient, concerns with patient medication adherence, and practice type. Clinicians endorsed electronic health record modifications and clinician prescribing feedback as methods to improve patient care and reduce the durations of prescribed antibiotics. Suggestions for intervention optimization and education needs were also obtained.
Conclusions:
Findings suggest that clinicians and administrators support reducing prescribed antibiotic durations for AOM and are receptive to the proposed interventions. More education is needed to increase parent awareness about antibiotic stewardship and AOM treatment options.
Clinical trials identifier:
RELAX: Reducing Length of Antibiotics for Children with Ear Infections (RELAX), NCT05608993, https://clinicaltrials.gov/study/NCT05608993.
An index is proposed to measure the extent of agreement of the data of a sociometric test with another test made at an earlier time or on another test criterion. The index is used to define an index of concordance between the two tests. It is shown how the index may be used for either individuals or groups. Tests of the hypothesis that agreement is random are given for all cases and applied to an example.
The variance of the number of mutual dyads in a sociometric situation where each member of a group chooses independently and at random is derived for unrestricted numbers of choices per group member, as well as for a fixed number of choices. The distribution of the number of mutuals is considered.
A new criterion for rotation to an oblique simple structure is proposed. The results obtained are similar to that obtained by Cattell and Muerle's maxplane criterion. Since the proposed criterion is smooth it is possible to locate the local maxima using simple gradient techniques. The results of the application of the Functionplane criterion to three sets of data are given. In each case a better fit to the subjective solution was obtained using the functionplane criterion than was reported for by Hakstian for the oblimax, promax, maxplane, or the Harris-Kaiser methods.
To explain changes in the sociometric configuration of a group through time, a problem arises of the extent to which such changes may be viewed as the aggregation of part-processes occurring at the level of two-person choice structures. A possible model is a Markov chain in which three possible states are mutual choice, one-way choice, and indifference, one realization for each pair of choosing individuals in the group. Choice data for an eighth-grade classroom are fitted to this model and are used to answer questions of constancy of transition probabilities, order of the chain, and sex differences.