4,584 research outputs found
Multimorbidity patterns and risk of hospitalisation in children: A population cohort study of 3.6 million children in England, with illustrative examples from childhood cancer survivors
Background: Population-level estimates of hospitalisation risk in children are currently limited. The study aims to characterise morbidity patterns in all children, focusing on childhood cancer survivors versus children without cancer. Methods: Employing hospital records of children aged <19 years between 1997 to 2018 in England, we characterised morbidity patterns in childhood cancer survivors compared with children without cancer. The follow-up began on the 5th anniversary of the index hospitalisation and the primary outcome was the incidence of comorbidities. Findings: We identified 3,559,439 eligible participants having 12,740,666 hospital admissions, with a mean age at study entry of 11.2 years. We identified 32,221 patients who survived for at least 5 years since their initial cancer diagnosis. During the follow-up period and within the whole population of 3.6 million children, the leading conditions for admission were (i) metabolic, endocrine, digestive renal and genitourinary conditions (84,749, 2.5%), (ii) neurological (35,833, 1.0%) and (iii) musculoskeletal or skin conditions (23,574, 0.7%), fever, acute respiratory and sepsis (22,604, 0.7%). Stratified analyses revealed that females and children from socioeconomically deprived areas had a higher cumulative incidence for morbidities requiring hospitalisation (p < 0.001). At baseline (5 years after the initial cancer diagnosis or initial hospitalisation for survivors and population comparisons, respectively), cancer survivors experienced a higher prevalence of individual conditions and multimorbidity (≥ 2 morbidities) compared with children without cancer. Cox regression analyses showed that survivors had at least a 4-fold increase in the risk of hospitalisation for conditions such as chronic eye conditions (hazard ration (HR):4.0, 95% confidence interval (CI): 3.5-4.7), fever requiring hospitalisation (HR: 4.4, 95% CI: 3.8-5.0), subsequent neoplasms (HR: 5.7, 95% CI:5.0-6.5), immunological disorders (HR: 6.5, 95% CI:4.5-9.3) and metabolic conditions (HR: 7.1, 95% CI:5.9-8.5). Interpretation: The overall morbidity burden among children was low in general; however, childhood cancer survivors experienced a higher prevalence and subsequent risk of hospitalisation for a range of morbidities. Targeted policies may be required to promote awareness on health vulnerabilities and gender disparity and to improve advocacy for healthcare in deprived communities. Funding: Wellcome Trust, National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre, NIHR Great Ormond Street Hospital Biomedical Research Centre and Academy of Medical Sciences. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report
Leg disorders in broiler chickens : prevalence, risk factors and prevention
Broiler (meat) chickens have been subjected to intense genetic selection. In the past 50 years, broiler growth rates have increased
by over 300% (from 25 g per day to 100 g per day). There is growing societal concern that many broiler chickens have impaired
locomotion or are even unable to walk. Here we present the results of a comprehensive survey of commercial flocks which
quantifies the risk factors for poor locomotion in broiler chickens.We assessed the walking ability of 51,000 birds, representing 4.8
million birds within 176 flocks.We also obtained information on approximately 150 different management factors associated with
each flock. At a mean age of 40 days, over 27.6% of birds in our study showed poor locomotion and 3.3% were almost unable to
walk. The high prevalence of poor locomotion occurred despite culling policies designed to remove severely lame birds from
flocks. We show that the primary risk factors associated with impaired locomotion and poor leg health are those specifically
associated with rate of growth. Factors significantly associated with high gait score included the age of the bird (older birds), visit
(second visit to same flock), bird genotype, not feeding whole wheat, a shorter dark period during the day, higher stocking density
at the time of assessment, no use of antibiotic, and the use of intact feed pellets. The welfare implications are profound. Worldwide
approximately 261010 broilers are reared within similar husbandry systems.We identify a range of management factors that could
be altered to reduce leg health problems, but implementation of these changes would be likely to reduce growth rate and
production. A debate on the sustainability of current practice in the production of this important food source is required
An exploratory randomised controlled trial of a premises-level intervention to reduce alcohol-related harm including violence in the United Kingdom
<b>Background</b><p></p>
To assess the feasibility of a randomised controlled trial of a licensed premises intervention to reduce severe intoxication and disorder; to establish effect sizes and identify appropriate approaches to the development and maintenance of a rigorous research design and intervention implementation.<p></p>
<b>Methods</b><p></p>
An exploratory two-armed parallel randomised controlled trial with a nested process evaluation. An audit of risk factors and a tailored action plan for high risk premises, with three month follow up audit and feedback. Thirty-two premises that had experienced at least one assault in the year prior to the intervention were recruited, match paired and randomly allocated to control or intervention group. Police violence data and data from a street survey of study premises’ customers, including measures of breath alcohol concentration and surveyor rated customer intoxication, were used to assess effect sizes for a future definitive trial. A nested process evaluation explored implementation barriers and the fidelity of the intervention with key stakeholders and senior staff in intervention premises using semi-structured interviews.<p></p>
<b>Results</b><p></p>
The process evaluation indicated implementation barriers and low fidelity, with a reluctance to implement the intervention and to submit to a formal risk audit. Power calculations suggest the intervention effect on violence and subjective intoxication would be raised to significance with a study size of 517 premises.<p></p>
<b>Conclusions</b><p></p>
It is methodologically feasible to conduct randomised controlled trials where licensed premises are the unit of allocation. However, lack of enthusiasm in senior premises staff indicates the need for intervention enforcement, rather than voluntary agreements, and on-going strategies to promote sustainability
Counterflow dielectrophoresis for trypanosome enrichment and detection in blood
Human African trypanosomiasis or sleeping sickness is a deadly disease endemic in sub-Saharan Africa, caused by single-celled protozoan parasites. Although it has been targeted for elimination by 2020, this will only be realized if diagnosis can be improved to enable identification and treatment of afflicted patients. Existing techniques of detection are restricted by their limited field-applicability, sensitivity and capacity for automation. Microfluidic-based technologies offer the potential for highly sensitive automated devices that could achieve detection at the lowest levels of parasitemia and consequently help in the elimination programme. In this work we implement an electrokinetic technique for the separation of trypanosomes from both mouse and human blood. This technique utilises differences in polarisability between the blood cells and trypanosomes to achieve separation through opposed bi-directional movement (cell counterflow). We combine this enrichment technique with an automated image analysis detection algorithm, negating the need for a human operator
A sex-influenced flexible foraging strategy in a tropical seabird, the magnificent frigatebird
© The authors and the University of Liverpool 2019. To successfully exploit resources, animals must be adapted to operate under phenotypic and environmental constraints. The strategies that predators use to locate prey are therefore diverse, particularly for breeding central-place foragers that must balance investment in reproduction and self-maintenance. Magnificent frigatebirds Fregata magnificens are tropical seabirds with intriguing morphology and feeding ecology, which display strikingly unequal levels of parental care (males deserting offspring months before females). These unusual traits can better help us understand the links between movement behaviour and breeding strategies in this poorly studied species. Using archival GPS, GPS-GSM loggers, bird-borne cameras and dietary data, we investigated the foraging ecology of chick-rearing magnificent frigatebirds from a breeding population in the Cayman Islands. This population engages in 2 main foraging strategies: (1) coastal trips over the continental shelf, where individuals target reef species and engage in kleptoparasitism, and (2) offshore trips during which birds feed on schooling pelagic prey. Differences in strategy use were partially linked to sex, with males (which invest less in offspring) roaming further from nests, and showing a higher propensity to forage offshore. Video data further indicated differences in social information use between strategies: foraging with conspecifics was more prevalent in coastal environments than pelagic. We suggest that observed variation in at-sea behaviour may partially be mediated by sex-based differences in parental roles, and/or size differences leading to intraspecific competition. Our study provides evidence of bimodal foraging and sheds new light on the importance of both pelagic and coastal feeding in this enigmatic species
Transfer RNA-derived small RNAs in the cancer transcriptome
The cellular lifetime includes stages such as differentiation, proliferation, division, senescence and apoptosis.These stages are driven by a strictly ordered process of transcription dynamics. Molecular disruption to RNA polymerase assembly, chromatin remodelling and transcription factor binding through to RNA editing, splicing, post-transcriptional regulation and ribosome scanning can result in significant costs arising from genome instability. Cancer development is one example of when such disruption takes place. RNA silencing is a term used to describe the effects of post-transcriptional gene silencing mediated by a diverse set of small RNA molecules. Small RNAs are crucial for regulating gene expression and microguarding genome integrity.RNA silencing studies predominantly focus on small RNAs such as microRNAs, short-interfering RNAs and piwi-interacting RNAs. We describe an emerging renewal of inter-est in a‘larger’small RNA, the transfer RNA (tRNA).Precisely generated tRNA-derived small RNAs, named tRNA halves (tiRNAs) and tRNA fragments (tRFs), have been reported to be abundant with dysregulation associated with cancer. Transfection of tiRNAs inhibits protein translation by displacing eukaryotic initiation factors from messenger RNA (mRNA) and inaugurating stress granule formation.Knockdown of an overexpressed tRF inhibits cancer cell proliferation. Recovery of lacking tRFs prevents cancer metastasis. The dual oncogenic and tumour-suppressive role is typical of functional small RNAs. We review recent reports on tiRNA and tRF discovery and biogenesis, identification and analysis from next-generation sequencing data and a mechanistic animal study to demonstrate their physiological role in cancer biology. We propose tRNA-derived small RNA-mediated RNA silencing is an innate defence mechanism to prevent oncogenic translation. We expect that cancer cells are percipient to their ablated control of transcription and attempt to prevent loss of genome control through RNA silencing
Routine testing for IgG antibodies against hepatitis A virus in Israel
BACKGROUND: Viral hepatitis is highly endemic in Israel, with the hepatitis A virus (HAV) responsible for most cases. Improved socioeconomic factors, as well as the universal vaccination of infants (introduced in 1999) has resulted in a decline in infection rates in Israel. This study examines the benefits of routine testing for anti-HAV IgG in high-risk population. METHODS: A retrospective examination of the files of teenage and adult patients (aged 16–99 years; mean 33.9) in two primary care clinics found 1,017 patients who had been tested for anti-HAV IgG antibodies for either general healthcare screening or ongoing follow-up for chronic illness. Seropositive patients were then asked regarding recall of past hepatitis (i.e. jaundice, regardless of viral etiology); post-exposure prophylaxis with immune serum immunoglobulin (ISG); and active immunization with inactivated virus. Seronegative patients were subsequently sent for active immunization. RESULTS: Of the1,017 patient records studied (503 male, 514 female), a total of 692 were seropositive (354 males, 338 females; P = 0.113). Seropositivity rates increased with age (p < 0.005), and were highest among those born in Middle Eastern countries other than Israel (91.3%) and lowest among immigrants from South America (44.1%; P < 0.005). 456 of the seropositive patients were interviewed, of whom only 91 recalled past illness while 103 remembered receiving post-exposure prophylaxis (ISG) and 8 active vaccination. Those who were unaware of past infection were more likely to have been vaccinated with ISG than those who were aware (26.3% vs. 7.7%; p < 0.005). CONCLUSION: The relatively high prevalence rate of anti-HAV seropositivity in our study may me due to the fact that the study was conducted in a primary care clinic or that it took place in Jerusalem, a relatively poor and densely populated Israeli city. Most of the seropostive patients had no recollection of prior infection, which can be explained by the fact that most hepatitis A infections occur during childhood and are asymptomatic. Routine testing for anti-HAV IgG in societies endemic for HAV would help prevent seropositive patients from receiving either post-exposure or preventive immunization and target seronegative patients for preventive vaccination
Cosmic strings from pseudo-anomalous Fayet-Iliopoulos U(1) in D3/D7 brane inflation
We examine the consequences of recent developments on Fayet-Iliopoulos (FI)
terms for D-term inflationary models. There is currently no known way to couple
constant FI terms to supergravity consistently; only field-dependent FI terms
are allowed. These are natural in string theory and we argue that the FI term
in D3/D7 inflation turns out to be of this type, corresponding to a
pseudo-anomalous U(1). T he anomaly is canceled by the Green-Schwarz mechanism
in 4 dimensions. Inflation proceeds as usual, except that the scale is set by
the GS parameter. Cosmic strings resulting from a pseudo-anomalous U(1) have
potentially interesting characteristics. Originally expected to be global, they
turn out to be local in the string theory context and can support currents. We
outline the nature of these strings, discuss bounds on their formation, and
summarize resulting cosmological consequences.Comment: 10 pages; minor changes to match published versio
Effect on survey response rate of hand written versus printed signature on a covering letter: randomised controlled trial [ISRCTN67566265]
BACKGROUND: It is important that response rates to postal surveys are as high as possible to ensure that the results are representative and to maximise statistical power. Previous research has suggested that any personalisation of approach helps to improve the response rate. This experiment tested whether personalising questionnaires by hand signing the covering letter improved the response rate compared with a non-personalised group where the investigator's signature on the covering letter was scanned into the document and printed. METHODS: Randomised controlled trial. Questionnaires about surgical techniques of caesarean section were mailed to 3,799 Members and Fellows of the Royal College of Obstetricians and Gynaecologists resident in the UK. Individuals were randomly allocated to receive a covering letter with either a computer printed signature or a hand written signature. Two reminders were sent to non-respondents. The outcome measures were the proportion of questionnaires returned and their time to return. RESULTS: The response rate was 79.1% (1506/1905) in the hand-signed group and 78.4% (1484/1894) in the scanned and printed signature group. There was no detectable difference between the groups in response rate or time taken to respond. CONCLUSION: No advantage was detected to hand signing the covering letter accompanying a postal questionnaire to health professionals
The role of mentorship in protege performance
The role of mentorship on protege performance is a matter of importance to
academic, business, and governmental organizations. While the benefits of
mentorship for proteges, mentors and their organizations are apparent, the
extent to which proteges mimic their mentors' career choices and acquire their
mentorship skills is unclear. Here, we investigate one aspect of mentor
emulation by studying mentorship fecundity---the number of proteges a mentor
trains---with data from the Mathematics Genealogy Project, which tracks the
mentorship record of thousands of mathematicians over several centuries. We
demonstrate that fecundity among academic mathematicians is correlated with
other measures of academic success. We also find that the average fecundity of
mentors remains stable over 60 years of recorded mentorship. We further uncover
three significant correlations in mentorship fecundity. First, mentors with
small mentorship fecundity train proteges that go on to have a 37% larger than
expected mentorship fecundity. Second, in the first third of their career,
mentors with large fecundity train proteges that go on to have a 29% larger
than expected fecundity. Finally, in the last third of their career, mentors
with large fecundity train proteges that go on to have a 31% smaller than
expected fecundity.Comment: 23 pages double-spaced, 4 figure
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