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The battles over official secrecy have to be fought on many different fronts. In the United Kingdom—whose ministers and public servants allegedly have a “passion for secrecy”—this was more than usually evident during 1967. Two pieces of legislation—namely, the Parliamentary Commissioner Act, 1967 (U.K.) and the Public Records Act, 1967 (Eng.)—represented a modest triumph for those who would wish to see more light shed upon the affairs of the nation. Elsewhere the picture was rather more familiar. The Security Commission recommended a further tightening of documentary security in the Cabinet Office; this followed upon the conviction under the Official Secrets Acts, 1911 to 1939 (U.K.) of a young typist in the Cabinet Office, “the first known occasion on which classified papers have been extracted from” this inner sanctum of government.
Cancer is associated with physical, social, spiritual, and psychological changes in patients and their caregivers. However, in sub-Saharan Africa, there is lack of evidence on the impact of gender, social norms, and relationship dynamics in the face of terminal illness. The aim of this paper is to explore how gender identity, social norms, and power relations are impacted when a person is living in Uganda with advanced cancer.
Methods
Focus groups with adult men and women living with advanced cancer in Uganda were conducted. Interviews explored the social effects of cancer and common challenges, including how both disease and treatment affect the patient and marital relationships within their families. Participants’ recommendations were sought to improve the social well-being of patients and their families. Data were analyzed using inductive thematic analysis.
Results
Men and women experienced negative changes in their roles and identities, often feeling unable to fulfill their marital duties in terms of intimacy, their social roles and responsibilities based on societal expectations. Men expressed loss of a “masculine” identity when unable to provide economically for the household. This led to tension in the familial power dynamics, contributing to relationship breakdown and gender-based violence (GBV) against spouses. Women noted challenges with parenting, relationship breakdowns, and increased GBV.
Significance of results
Gender impacts the patient and the family dynamic throughout the life course, including during advanced cancer. Patients and caregivers experience a change in their roles and identities while coping with existential distress and end-of-life tasks. Given these results, gender considerations and dynamics should be incorporated into overall palliative care provision. In addition, there is a need to integrate GBV screening and support in cancer services to address social health and safety needs in the context of serious illness.
This study evaluated the impact of 2015/2016 prescribing guidance on antidepressant prescribing choices in children.
Methods
A retrospective e-cohort study of whole population routine electronic healthcare records was conducted. Poisson regression was undertaken to explore trends over time for depression, antidepressant prescribing, indications and secondary care contacts. Time trend analysis was conducted to assess the impact of guidance.
Results
A total of 643 322 primary care patients in Wales UK, aged 6–17 years from 2010–2019 contributed 3 215 584 person-years of follow-up. Adjusted incidence of depression more than doubled (IRR for 2019 = 2.8 [2.5–3.2]) with similar trends seen for antidepressants. Fluoxetine was the most frequently prescribed first-line antidepressant. Citalopram comprised less than 5% of first prescriptions in younger children but 22.9% (95% CI 22.0–23.8; 95% CI 2533) in 16–17-year-olds. Approximately half of new antidepressant prescribing was associated with depression. Segmented regression analysis showed that prescriptions of ‘all’ antidepressants, Fluoxetine and Sertraline were increasing before the guidance. This upward trend flattened for both ‘all’ antidepressants and Fluoxetine and steepened for Sertraline. Citalopram prescribing was decreasing significantly pre guidance being issued with no significant change afterward.
Conclusions
Targeted intervention is needed to address rising rates of depression in children. Practitioners are partially adhering to local and national guidance. The decision-making process behind prescribing choices is likely to be multi-factorial. Activities to support implementation of guidance should be adopted in relation to safety in prescribing of antidepressants in children including timely availability of talking therapies and specialist mental health services.
A nonparametric test of dispersion with paired replicates data is described which involves jackknifing logarithmic transformations of the ratio of variance estimates for the pre- and post-treatment populations. Results from a Monte Carlo simulation show that the test performs well under Ho and has good power properties. Examples are given of applying the procedure on psychiatric data.
The use of U-statistics based on rank correlation coefficients in estimating the strength of concordance among a group of rankers is examined for cases where the null hypothesis of random rankings is not tenable. The studentized U-statistics is asymptotically distribution-free, and the Student-t approximation is used for small and moderate sized samples. An approximate confidence interval is constructed for the strength of concordance. Monte Carlo results indicate that the Student-t approximation can be improved by estimating the degrees of freedom.
Indexes of skewness and kurtosis for a test-score distribution are expressed in terms of item parameters. Both are shown to depend, in part, on item means, variances, and covariances. The index of skewness depends also on trivariances. A trivariance is a product moment involving first powers of deviation scores for three items. The index of kurtosis depends on quadrivariances, as well as trivariances. A quadrivariance is a product moment involving first powers of deviation scores for four items. Empirical data are presented for responses of groups of subjects to 25 triads and 25 tetrads of items from five tests.
We present a re-discovery of G278.94+1.35a as possibly one of the largest known Galactic supernova remnants (SNRs) – that we name Diprotodon. While previously established as a Galactic SNR, Diprotodon is visible in our new Evolutionary Map of the Universe (EMU) and GaLactic and Extragalactic All-sky MWA (GLEAM) radio continuum images at an angular size of $3{{{{.\!^\circ}}}}33\times3{{{{.\!^\circ}}}}23$, much larger than previously measured. At the previously suggested distance of 2.7 kpc, this implies a diameter of 157$\times$152 pc. This size would qualify Diprotodon as the largest known SNR and pushes our estimates of SNR sizes to the upper limits. We investigate the environment in which the SNR is located and examine various scenarios that might explain such a large and relatively bright SNR appearance. We find that Diprotodon is most likely at a much closer distance of $\sim$1 kpc, implying its diameter is 58$\times$56 pc and it is in the radiative evolutionary phase. We also present a new Fermi-LAT data analysis that confirms the angular extent of the SNR in gamma rays. The origin of the high-energy emission remains somewhat puzzling, and the scenarios we explore reveal new puzzles, given this unexpected and unique observation of a seemingly evolved SNR having a hard GeV spectrum with no breaks. We explore both leptonic and hadronic scenarios, as well as the possibility that the high-energy emission arises from the leftover particle population of a historic pulsar wind nebula.
Clostridioides difficile (C. difficile) is one of the most common causes of healthcare-associated infections (HAIs). Elimination of C. difficile spores is difficult as they are resistant to common hospital-grade disinfectants. Copper-impregnated surfaces provide continuous reduction of multiple pathogens, potentially lowering the risk of infections. This manuscript aims to evaluate the efficacy of copper-impregnated surfaces on C. difficile spores.
Methods:
Control (no copper) coupons and copper coupons containing 20% copper-oxide were inoculated with C. difficile spore loads ranging from 105 to 107 spores, with or without 5% fetal bovine serum soil load. After 4 hours of contact time, the C. difficile spores were recovered, plated on C. difficile growth media, and colony forming units were counted. The efficacy of copper (log10 kill) was estimated using a Bayesian latent variables model.
Results:
After 4 hours, unsoiled copper bedrail and copper table coupons at mean spore inoculation resulted in a 97.3% and 96.8% reduction in spore count (1.57 and 1.50 log10 kill, respectively). That of soiled bedrail and table coupons showed a 91.8% and 91.7% reduction (1.10 and 1.10 log10 kill, respectively).
Conclusions:
Copper coupons can substantially reduce C. difficile spores after 4 hours, but results vary depending on the initial spore concentration and presence or absence of organic material. Higher initial spore loads or excess organic material may prevent spores from contact with copper surfaces, thus decreasing kill efficacy. Continuous sporicidal effect of copper-impregnated surfaces may decrease spore burden and help prevent transmission of spores.
The validity of conclusions drawn from specific research studies must be evaluated in light of the purposes for which the research was undertaken. We distinguish four general types of research: description and point estimation, correlation and prediction, causal inference, and explanation. For causal and explanatory research, internal validity is critical – the extent to which a causal relationship can be inferred from the results of variation in the independent and dependent variables of an experiment. Random assignment is discussed as the key to avoiding threats to internal validity. Internal validity is distinguished from construct validity (the relationship between a theoretical construct and the methods used to operationalize that concept) and external validity (the extent to which the results of a research study can be generalized to other contexts). Construct validity is discussed in terms of multiple operations and discriminant and convergent validity assessment. External validity is discussed in terms of replicability, robustness, and relevance of specific research findings.
Motor neuron disease (MND) is a progressive, fatal, neurodegenerative condition that affects motor neurons in the brain and spinal cord, resulting in loss of the ability to move, speak, swallow and breathe. Acceptance and commitment therapy (ACT) is an acceptance-based behavioural therapy that may be particularly beneficial for people living with MND (plwMND). This qualitative study aimed to explore plwMND’s experiences of receiving adapted ACT, tailored to their specific needs, and therapists’ experiences of delivering it.
Method:
Semi-structured qualitative interviews were conducted with plwMND who had received up to eight 1:1 sessions of adapted ACT and therapists who had delivered it within an uncontrolled feasibility study. Interviews explored experiences of ACT and how it could be optimised for plwMND. Interviews were audio recorded, transcribed and analysed using framework analysis.
Results:
Participants were 14 plwMND and 11 therapists. Data were coded into four over-arching themes: (i) an appropriate tool to navigate the disease course; (ii) the value of therapy outweighing the challenges; (iii) relevance to the individual; and (iv) involving others. These themes highlighted that ACT was perceived to be acceptable by plwMND and therapists, and many participants reported or anticipated beneficial outcomes in the future, despite some therapeutic challenges. They also highlighted how individual factors can influence experiences of ACT, and the potential benefit of involving others in therapy.
Conclusions:
Qualitative data supported the acceptability of ACT for plwMND. Future research and clinical practice should address expectations and personal relevance of ACT to optimise its delivery to plwMND.
Key learning aims
(1) To understand the views of people living with motor neuron disease (plwMND) and therapists on acceptance and commitment therapy (ACT) for people living with this condition.
(2) To understand the facilitators of and barriers to ACT for plwMND.
(3) To learn whether ACT that has been tailored to meet the specific needs of plwMND needs to be further adapted to potentially increase its acceptability to this population.
Scholarly activity is a key component of most residency programmes. To establish fundamental research skills and fill gaps within training curricula, we developed an online, asynchronous set of modules called Research 101 to introduce trainees to various topics that are germane to the conduct of research and evaluated its effectiveness in resident research education. Research 101 was utilised by residents at One Brooklyn Health in Brooklyn, NY. Resident knowledge, confidence, and satisfaction were assessed using pre- and post-module surveys with 5-point Likert scaled questions, open-ended text responses, and a multiple-choice quiz. Pre-module survey results indicated that residents were most confident with the Aligning expectations, Introduction to research, and Study design and data analysis basics modules and least confident with the Submitting an Institutional Review Board protocol and Presenting your summer research modules. Post-module survey responses demonstrated increased learning compared to pre-module results for all modules and learning objectives (p < 0.0001). “This module met my needs” was endorsed 91.4% of the time. The median score for the final quiz that consisted of 25 multiple-choice questions was 23. Thematic analysis of open-ended post-module survey responses identified multiple strengths and opportunities for improvement in course content and instructional methods. These data demonstrate that residents benefit from completion of Research 101, as post-module survey scores were significantly higher than pre-module survey scores for all modules and questions, final quiz scores were high, and open-ended responses highlighted opportunities for additional resident learning.
Organic sweetpotato growers have limited effective weed management options, and most rely on in-season between-row cultivation and hand weeding, which are time consuming, are costly, and deteriorate soil quality. Studies were conducted at the Samuel G. Meigs Horticulture Research Farm, Lafayette, IN, and at the Southwest Purdue Agricultural Center, Vincennes, IN, in 2022 and 2023 to determine the effects of in-row plant spacing and cultivar selection on weed suppression and organic sweetpotato yield. The experiment was a split-split plot design, with in-row spacings of 20, 30, and 40 cm as the main plot factor, weeding frequency (critical weed-free period and weed-free) as the subplot factor, and sweetpotato cultivar (‘Covington’ and ‘Monaco’) as the sub-subplot factor. However, in 2022, we evaluated only in-row spacing and weeding frequency because of the poor establishment of ‘Monaco’. In 2023, sweetpotato canopy at 5 wk after transplanting (WAP) decreased as in-row spacing increased from 20 to 40 cm, and sweetpotato canopy cover of ‘Monaco’ (62%) was greater than that of ‘Covington’ (44%). In-row spacing did not affect weed density at 4, 5, and 6 WAP. As in-row spacing increased from 20 to 40 cm, total sweetpotato yield pooled across both locations in 2023 decreased from 30,223 to 21,209 kg ha−1 for ‘Covington’ and from 24,370 to 20,848 kg ha−1 for ‘Monaco’; however, jumbo yield increased for both cultivars. Findings from this study suggest that an in-row spacing of 20 cm may provide greater yield than the standard spacing of 30 cm for both ‘Monaco’ and ‘Covington’.
Accelerating COVID-19 Treatment Interventions and Vaccines (ACTIV) was initiated by the US government to rapidly develop and test vaccines and therapeutics against COVID-19 in 2020. The ACTIV Therapeutics-Clinical Working Group selected ACTIV trial teams and clinical networks to expeditiously develop and launch master protocols based on therapeutic targets and patient populations. The suite of clinical trials was designed to collectively inform therapeutic care for COVID-19 outpatient, inpatient, and intensive care populations globally. In this report, we highlight challenges, strategies, and solutions around clinical protocol development and regulatory approval to document our experience and propose plans for future similar healthcare emergencies.
We consider the debut of a new monetary instrument, central bank digital currencies (CBDCs). Drawing on examples from monetary history, we argue that a successful monetary transformation must combine microeconomic efficiency with macroeconomic credibility. A paradoxical feature of these transformations is that success in the micro dimension can encourage macro failure. Overcoming this paradox may require politically uncomfortable compromises. We propose that such compromises will be necessary for the success of CBDCs.
Major depressive disorder (MDD) is the leading cause of disability globally, with moderate heritability and well-established socio-environmental risk factors. Genetic studies have been mostly restricted to European settings, with polygenic scores (PGS) demonstrating low portability across diverse global populations.
Methods
This study examines genetic architecture, polygenic prediction, and socio-environmental correlates of MDD in a family-based sample of 10 032 individuals from Nepal with array genotyping data. We used genome-based restricted maximum likelihood to estimate heritability, applied S-LDXR to estimate the cross-ancestry genetic correlation between Nepalese and European samples, and modeled PGS trained on a GWAS meta-analysis of European and East Asian ancestry samples.
Results
We estimated the narrow-sense heritability of lifetime MDD in Nepal to be 0.26 (95% CI 0.18–0.34, p = 8.5 × 10−6). Our analysis was underpowered to estimate the cross-ancestry genetic correlation (rg = 0.26, 95% CI −0.29 to 0.81). MDD risk was associated with higher age (beta = 0.071, 95% CI 0.06–0.08), female sex (beta = 0.160, 95% CI 0.15–0.17), and childhood exposure to potentially traumatic events (beta = 0.050, 95% CI 0.03–0.07), while neither the depression PGS (beta = 0.004, 95% CI −0.004 to 0.01) or its interaction with childhood trauma (beta = 0.007, 95% CI −0.01 to 0.03) were strongly associated with MDD.
Conclusions
Estimates of lifetime MDD heritability in this Nepalese sample were similar to previous European ancestry samples, but PGS trained on European data did not predict MDD in this sample. This may be due to differences in ancestry-linked causal variants, differences in depression phenotyping between the training and target data, or setting-specific environmental factors that modulate genetic effects. Additional research among under-represented global populations will ensure equitable translation of genomic findings.
Depression is an independent risk factor for cardiovascular disease (CVD), but it is unknown if successful depression treatment reduces CVD risk.
Methods
Using eIMPACT trial data, we examined the effect of modernized collaborative care for depression on indicators of CVD risk. A total of 216 primary care patients with depression and elevated CVD risk were randomized to 12 months of the eIMPACT intervention (internet cognitive-behavioral therapy [CBT], telephonic CBT, and select antidepressant medications) or usual primary care. CVD-relevant health behaviors (self-reported CVD prevention medication adherence, sedentary behavior, and sleep quality) and traditional CVD risk factors (blood pressure and lipid fractions) were assessed over 12 months. Incident CVD events were tracked over four years using a statewide health information exchange.
Results
The intervention group exhibited greater improvement in depressive symptoms (p < 0.01) and sleep quality (p < 0.01) than the usual care group, but there was no intervention effect on systolic blood pressure (p = 0.36), low-density lipoprotein cholesterol (p = 0.38), high-density lipoprotein cholesterol (p = 0.79), triglycerides (p = 0.76), CVD prevention medication adherence (p = 0.64), or sedentary behavior (p = 0.57). There was an intervention effect on diastolic blood pressure that favored the usual care group (p = 0.02). The likelihood of an incident CVD event did not differ between the intervention (13/107, 12.1%) and usual care (9/109, 8.3%) groups (p = 0.39).
Conclusions
Successful depression treatment alone is not sufficient to lower the heightened CVD risk of people with depression. Alternative approaches are needed.
The authors report on ancient DNA data from two human skeletons buried within the chancel of the 1608–1616 church at the North American colonial settlement of Jamestown, Virginia. Available archaeological, osteological and documentary evidence suggest that these individuals are Sir Ferdinando Wenman and Captain William West, kinsmen of the colony's first Governor, Thomas West, Third Baron De La Warr. Genomic analyses of the skeletons identify unexpected maternal relatedness as both carried the mitochondrial haplogroup H10e. In this unusual case, aDNA prompted further historical research that led to the discovery of illegitimacy in the West family, an aspect of identity omitted, likely intentionally, from genealogical records.
The oxidative power of a smectite can be measured quantitatively by oxidation of hydro-quinone to p-benzoquinone in a clay slurry. Oxidation takes place in the presence of O2 (air) but not N2 unless Fe3+ or Cu2+ are the exchangeable cations. This study examined 26 smectite samples with varying compositions and processing. The oxidative power increases with decreasing Li-fixation and increasing cation exchange capacity. Li-fixation does not depend upon the tetrahedral Al. The cation exchange capacity can decrease markedly by mere storage in water.
The oxidation proceeds principally on the surface by adsorbed oxygen molecules or radicals. A mechanism is proposed. With Fe3+ or Cu2+ present, even under N2, oxidation occurs via electron transfer. With smectites containing Fe2+, both the Fe and the hydroquinone are oxidized in the same reaction.