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To investigate the symptoms of SARS-CoV-2 infection, their dynamics and their discriminatory power for the disease using longitudinally, prospectively collected information reported at the time of their occurrence. We have analysed data from a large phase 3 clinical UK COVID-19 vaccine trial. The alpha variant was the predominant strain. Participants were assessed for SARS-CoV-2 infection via nasal/throat PCR at recruitment, vaccination appointments, and when symptomatic. Statistical techniques were implemented to infer estimates representative of the UK population, accounting for multiple symptomatic episodes associated with one individual. An optimal diagnostic model for SARS-CoV-2 infection was derived. The 4-month prevalence of SARS-CoV-2 was 2.1%; increasing to 19.4% (16.0%–22.7%) in participants reporting loss of appetite and 31.9% (27.1%–36.8%) in those with anosmia/ageusia. The model identified anosmia and/or ageusia, fever, congestion, and cough to be significantly associated with SARS-CoV-2 infection. Symptoms’ dynamics were vastly different in the two groups; after a slow start peaking later and lasting longer in PCR+ participants, whilst exhibiting a consistent decline in PCR- participants, with, on average, fewer than 3 days of symptoms reported. Anosmia/ageusia peaked late in confirmed SARS-CoV-2 infection (day 12), indicating a low discrimination power for early disease diagnosis.
Increasing litter size has long been a goal of pig breeders and producers, and may have implications for pig (Sus scrofa domesticus) welfare. This paper reviews the scientific evidence on biological factors affecting sow and piglet welfare in relation to large litter size. It is concluded that, in a number of ways, large litter size is a risk factor for decreased animal welfare in pig production. Increased litter size is associated with increased piglet mortality, which is likely to be associated with significant negative animal welfare impacts. In surviving piglets, many of the causes of mortality can also occur in non-lethal forms that cause suffering. Intense teat competition may increase the likelihood that some piglets do not gain adequate access to milk, causing starvation in the short term and possibly long-term detriments to health. Also, increased litter size leads to more piglets with low birth weight which is associated with a variety of negative long-term effects. Finally, increased production pressure placed on sows bearing large litters may produce health and welfare concerns for the sow. However, possible biological approaches to mitigating health and welfare issues associated with large litters are being implemented. An important mitigation strategy is genetic selection encompassing traits that promote piglet survival, vitality and growth. Sow nutrition and the minimisation of stress during gestation could also contribute to improving outcomes in terms of piglet welfare. Awareness of the possible negative welfare consequences of large litter size in pigs should lead to further active measures being taken to mitigate the mentioned effects.
Increasing litter size has long been a goal of pig (Sus scrofa domesticus) breeders and producers in many countries. Whilst this has economic and environmental benefits for the pig industry, there are also implications for pig welfare. Certain management interventions are used when litter size routinely exceeds the ability of individual sows to successfully rear all the piglets (ie viable piglets outnumber functional teats). Such interventions include: tooth reduction; split suckling; cross-fostering; use of nurse sow systems and early weaning, including split weaning; and use of artificial rearing systems. These practices raise welfare questions for both the piglets and sow and are described and discussed in this review. In addition, possible management approaches which might mitigate health and welfare issues associated with large litters are identified. These include early intervention to provide increased care for vulnerable neonates and improvements to farrowing accommodation to mitigate negative effects, particularly for nurse sows. An important concept is that management at all stages of the reproductive cycle, not simply in the farrowing accommodation, can impact on piglet outcomes. For example, poor stockhandling at earlier stages of the reproductive cycle can create fearful animals with increased likelihood of showing poor maternal behaviour. Benefits of good sow and litter management, including positive human-animal relationships, are discussed. Such practices apply to all production situations, not just those involving large litters. However, given that interventions for large litters involve increased handling of piglets and increased interaction with sows, there are likely to be even greater benefits for management of hyper-prolific herds.
Cross-sectional studies indicate that hippocampal function is abnormal across stages of psychosis. Neural theories of psychosis pathophysiology suggest that dysfunction worsens with illness stage. Here, we test the hypothesis that hippocampal function is impaired in the early stage of psychosis and declines further over the next 2 years.
Methods
We measured hippocampal function over 2 years using a scene processing task in 147 participants (76 individuals in the early stage of a non-affective psychotic disorder and 71 demographically similar healthy control individuals). Two-year follow-up was completed in 97 individuals (50 early psychosis, 47 healthy control). Voxelwise longitudinal analysis of activation in response to scenes was carried out within a hippocampal region of interest to test for group differences at baseline and a group by time interaction.
Results
At baseline, we observed lower anterior hippocampal activation in the early psychosis group relative to the healthy control group. Contrary to our hypothesis, hippocampal activation remained consistent and did not show the predicted decline over 2 years in the early psychosis group. Healthy controls showed a modest reduction in hippocampal activation after 2 years.
Conclusions
The results of this study suggest that hippocampal dysfunction in early psychosis does not worsen over 2 years and highlight the need for longer-term longitudinal studies.
Biospecimen repositories play a vital role in enabling investigation of biologic mechanisms, identification of disease-related biomarkers, advances in diagnostic assays, recognition of microbial evolution, and characterization of new therapeutic targets for intervention. They rely on the complex integration of scientific need, regulatory oversight, quality control in collection, processing and tracking, and linkage to robust phenotype information. The COVID-19 pandemic amplified many of these considerations and illuminated new challenges, all while academic health centers were trying to adapt to unprecedented clinical demands and heightened research constraints not witnessed in over 100 years. The outbreak demanded rapid understanding of SARS-CoV-2 to develop diagnostics and therapeutics, prompting the immediate need for access to high quality, well-characterized COVID-19-associated biospecimens. We surveyed 60 Clinical and Translational Science Award (CTSA) hubs to better understand the strategies and barriers encountered in biobanking before and in response to the COVID-19 pandemic. Feedback revealed a major shift in biorepository model, specimen-acquisition and consent process from a combination of investigator-initiated and institutional protocols to an enterprise-serving strategy. CTSA hubs were well equipped to leverage established capacities and expertise to quickly respond to the scientific needs of this crisis through support of institutional approaches in biorepository management.
Coworking spaces – the most prevalent form of collaborative workplaces – are said to offer the ideal solution for a new generation of creative knowledge workers, balancing flexibility and independence with structure and community. Recent studies, however, highlight deficiencies as they relate to the promise of ‘community’ made by most coworking spaces. This work reports 16 barriers that impede the process of human connectivity in coworking spaces that emerged from in-depth interviews with 26 coworkers. Suggestions are made for how these barriers might inform more effective workplace design.
The aim of this presentation is to summarize the results of the published systematic reviews / meta-analyses of the randomized controlled trials that have investigated the effectiveness of medications for the treatment of obsessive compulsive disorder (OCD) in children/adolescents and adults and to present preliminary results from a new review study using network meta-analytical techniques
Methods
Medline, Cochrane database, and the register of controlled trials maintained by the Cochrane Collaboration Depression, Anxiety & Neurosis Group (CCDAN) were searched for relevant trials, systematic reviews and/or meta-analyses.
Results
Regarding the new review study we were able to extract 103 pharmacological arms (preliminary results: 9 for Fluoxetine, 16 for Fluvoxamine, 11 for Paroxetine, 10 for Sertraline, 16 for Clomipramine, 7 for Citalopram / escitalopram, 2 for Venlafaxine, and 32 for Placebo) with a total number of 6572 patients randomized. The previous meta-analyses have confirmed the efficacy for all SSRIs and Clomipramine in all age groups while for other drugs further evidence is required. In the context of this presentation preliminary results of the relative efficacy of each drug, using network meta-analysis techniques will also be reported.
Conclusions
Several antidepressants have established their efficacy and acceptability for the management of non-resistant OCD. The major weakness of the literature so far is that head to head comparisons between antidepressants are few and therefore it is difficult to establish a clear hierarchy of the efficacy and acceptability of the various agents. This gap in the present literature will be filled by the present review.
This article presents the first fruits of a long-term project which aims to identify all the landholders named in Domesday Book, and to build up a picture of English landed society before and after the Norman conquest. The first part describes the project's methods and illustrates them with a selection of short profiles of individuals whose careers add distinctive colour to the emerging picture. The second offers firstly an analysis of the social distribution of landed wealth in England in 1066 and 1086, quantifying the numbers of landholders in different groups defined by the amount of the land assigned to them in Domesday. We then turn to a spatial analysis of landed society, using maps to illustrate the geographical distribution of landholding. In doing so, we offer fresh perspectives on the transformation of English landed society in the aftermath of conquest.
Severe longitudinally extensive transverse myelitis (LETM) can cause quadriplegia, marked sensory dysfunction, and respiratory failure. Some patients are unresponsive to conventional immune therapy. We report two cases of severe immune-mediated LETM requiring intensive care admission that failed to respond to high-dose corticosteroids, plasma exchange, intravenous immunoglobulin, and rituximab. Disease cessation and significant recovery was achieved after cyclophosphamide induction. In patients with severe acute immune-mediated LETM who fail to respond to corticosteroids and plasma exchange, cyclophosphamide induction should be considered. This agent and regimen provides a robust immunosuppressive response and can be induced rapidly. Cyclophosphamide effects and supportive evidence are discussed.
Validation-study data were analysed to investigate retention interval (RI) and prompt effects on the accuracy of fourth-grade children’s reports of school-breakfast and school-lunch (in 24-h recalls), and the accuracy of school-breakfast reports by breakfast location (classroom; cafeteria). Randomly selected fourth-grade children at ten schools in four districts were observed eating school-provided breakfast and lunch, and were interviewed under one of eight conditions created by crossing two RIs (‘short’ – prior-24-hour recall obtained in the afternoon and ‘long’ – previous-day recall obtained in the morning) with four prompts (‘forward’ – distant to recent, ‘meal name’ – breakfast, etc., ‘open’ – no instructions, and ‘reverse’ – recent to distant). Each condition had sixty children (half were girls). Of 480 children, 355 and 409 reported meals satisfying criteria for reports of school-breakfast and school-lunch, respectively. For breakfast and lunch separately, a conventional measure – report rate – and reporting-error-sensitive measures – correspondence rate and inflation ratio – were calculated for energy per meal-reporting child. Correspondence rate and inflation ratio – but not report rate – showed better accuracy for school-breakfast and school-lunch reports with the short RI than with the long RI; this pattern was not found for some prompts for each sex. Correspondence rate and inflation ratio showed better school-breakfast report accuracy for the classroom than for cafeteria location for each prompt, but report rate showed the opposite. For each RI, correspondence rate and inflation ratio showed better accuracy for lunch than for breakfast, but report rate showed the opposite. When choosing RI and prompts for recalls, researchers and practitioners should select a short RI to maximise accuracy. Recommendations for prompt selections are less clear. As report rates distort validation-study accuracy conclusions, reporting-error-sensitive measures are recommended.
We describe trends in incidence rates of methicillin-resistant Staphylococcus aureus (MRSA) in HIV-infected and HIV-uninfected patients enrolled in a large northern California Health Plan, and the ratio of MRSA to methicillin-susceptible S. aureus (MSSA) case counts. Between 1995 and 2010, 1549 MRSA infections were diagnosed in 14060 HIV-infected patients (11·0%) compared to 89546 MRSA infections in 6597396 HIV-uninfected patients (1·4%) (P = 0·00). A steady rise in MRSA infection rates began in 1995 in HIV-uninfected patients, peaking at 396·5 infections/100000 person-years in 2007. A more rapid rise in MRSA infection rates occurred in the HIV-infected group after 2000, peaking at 3592·8 infections/100000 in 2005. A declining trend in MRSA rates may have begun in 2008–2009. Comparing the ratio of MRSA to MSSA case counts, we observed that HIV-infected patients shouldered a greater burden of MRSA infection during most years of study follow-up compared to HIV-uninfected patients.
We investigated the effect of social inequalities on the uptake of human papillomavirus (HPV) vaccination, combining data from a feasibility study conducted in 2007–2008 in 2817 secondary schoolgirls in two UK primary-care trusts, with census and child health records. Uptake was significantly lower in more deprived areas (P<0·001) and in ethnic minority girls (P=0·013). The relatively small proportion of parents who actively refused vaccination by returning a negative consent form were more likely to come from more advantaged areas (P<0·001). Non-responding parents were from more deprived (P<0·001) and ethnic minority (P=0·001) backgrounds. Girls who did not receive HPV vaccination were less likely to have received all their childhood immunizations particularly measles, mumps and rubella (MMR). Different approaches may be needed to maximize HPV vaccine uptake in engaged and non-responding parents, including ethnic-specific approaches for non-responders.