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We report key learning from the public health management of the first two confirmed cases of COVID-19 identified in the UK. The first case imported, and the second associated with probable person-to-person transmission within the UK. Contact tracing was complex and fast-moving. Potential exposures for both cases were reviewed, and 52 contacts were identified. No further confirmed COVID-19 cases have been linked epidemiologically to these two cases. As steps are made to enhance contact tracing across the UK, the lessons learned from earlier contact tracing during the country's containment phase are particularly important and timely.
Exposure to prenatal hypoxia in rats leads to intrauterine growth restriction (IUGR), decreases fetal cardiomyocyte proliferation and increases the risk to develop cardiovascular diseases (CVD) later in life. The tumor necrosis factor-related weak inducer of apoptosis (TWEAK) induces cardiomyocyte proliferation through activation of the fibroblast growth factor-inducible molecule 14 (Fn-14) receptor. The TWEAK/Fn-14 pathway becomes quiescent shortly after birth, however, it becomes upregulated with CVD; suggesting that it could be a link between the increased susceptibility to CVD in pregnancies complicated by hypoxia/IUGR. We hypothesized that offspring exposed to prenatal hypoxia will exhibit reduced cardiomyocyte proliferation due to reduced Fn-14 expression and that the TWEAK/Fn-14 pathway will be expressed in those adult offspring. We exposed pregnant Sprague Dawley rats to control (21% oxygen) or hypoxic (11% oxygen) conditions from gestational days 15 to 21. Ventricular cardiomyocytes were isolated from male and female, control and hypoxic offspring at postnatal day 1. Proliferation was assessed in the presence or absence of r-TWEAK (72 h, 100 ng/ml). Prenatal hypoxia was not associated with differences in Fn-14 protein expression in either male or female offspring. Cardiomyocytes from prenatal hypoxic male, but not female, offspring had decreased proliferation compared with controls. Addition of r-TWEAK increased cardiomyocyte proliferation in all offspring. In adult offspring of all groups, the TWEAK/Fn-14 pathway was not detectable. Cardiomyocyte proliferation was reduced in only male offspring exposed to prenatal hypoxia but this was not due to changes in the Fn-14 pathway. Studies addressing other pathways associated with CVD and prenatal hypoxia are needed.
Ridgway’s Hawk Buteo ridgwayi is a Critically Endangered forest raptor endemic to the island of Hispaniola in the Caribbean. The species is currently limited to a small area on the north-east coast of the island, with fewer than 110 pairs remaining. From 2005 to 2009 we studied its breeding ecology, finding that Ridgway’s Hawks have a clutch size (2.0 ± 0.4 eggs) similar to other tropical raptors and island Buteo species. Fledging rate of 0.64 fledglings per active nest (fledgling nest-1) with pairs raising a single brood per year was also similar to that of other tropical Buteo species. Nest success was 40% (n = 151), with the majority of nest failures caused by human disturbance. The two significant predictors of nest success and fledging rate were related to human persecution: nest height and territory disturbance index. Pairs were able to tolerate human activity in their territory if there was no direct disturbance to the immediate nest area. Conservation planning for Ridgway’s Hawk must focus on community awareness programmes targeting local user groups within Los Haitises National Park regarding the uniqueness and endangered status of the hawk, and effective protection of the remaining karst forest in Los Haitises.
There has been a long history of herd health and production management programmes in many dairy industries around the world, but evidence for the efficacy of such programmes is limited. In response to a perceived decline in fertility of dairy cows, a herd reproductive management programme (InCalf) was introduced in New Zealand in 2007. This programme uses a management cycle approach that includes an assessment of the current herd status, identification of areas for improvement, development of a plan, implementation of this plan and finally a review process. The programme uses facilitators who work with farmers either in a one-to-one manner or in a formalised group setting that involves a series of meetings over a 12-month period (the farmer action group). The hypothesis that involvement in a reproductive management programme would improve herd reproductive performance was tested using a herd-level controlled randomised study (the National Herd Fertility Study) involving herds in four geographic regions of New Zealand over 2 years. Within each region, herds were ranked on the basis of the 6-week in-calf rate (i.e. the proportion of the herd pregnant in the first 6 weeks of the seasonal breeding programme) in the year preceding commencement of the study and then randomly assigned to be involved in a farmer action group or left as untreated controls. The key outcome variable of the study was the 6-week in-calf rate. Pregnancy diagnosis was undertaken at 12 weeks after the start of the seasonal breeding programme, which allowed determination of conception dates and hence calculation of the 6-week in-calf rate. Additional measurements including heifer live weight and body condition score (pre-calving and pre-mating) were undertaken to test whether treatment resulted in measurable changes in some of the key determinants of herd reproductive performance. Involvement in the farmer action group of InCalf resulted in a 2 percentage point increase in the 6-week in-calf rate (P=0.05). The following additional observations were made in herds involved in the farmer action group relative to control herds: heifers had live weight closer to target; the pre-mating body condition score of cows was higher; and oestrous detection rates were higher. It was concluded that involvement in this herd reproductive management programme improved reproductive outcomes in this New Zealand study. However, to achieve substantial improvements in herd reproductive performance at the regional or national level a greater response to the programme and a high uptake of such programmes is required, as well as use of other industry-level tools such as genetic management programmes.
Patterns of social organization and mating systems have been shown to be functions of ecological factors such as resource allocation and breeding density. In some species, particularly birds, social organization and genetic mating systems differ with molecular studies providing evidence of extra-pair young frequently occurring within broods of socially monogamous species. Here we examine the social and genetic mating system of an ecologically little-known forest raptor endemic to the island of Hispaniola in the Caribbean. From 2005–2009, our field observations of over 60 breeding pairs verified a social mating system of monogamy for the species. During the same time period, we collected blood samples (n = 146 birds, 48 nests) and used microsatellite profiles from 10 loci to estimate genetic relatedness among nestlings in a brood and assign putative fathers. We found no evidence of extra-pair paternity in 41 broods. We had one instance where a social male was not assigned as the putative father, however, the confidence level of this assignment was not significant since the genotypes of the social and assigned males were very similar. Our results support our hypothesis that genetic monogamy would be exhibited by Ridgway's hawk, an island-endemic tropical raptor.
A life-course approach to reduction of risk of non-communicable diseases (NCD) suggests that early-life interventions may be more effective than lifestyle modifications in middle age. Knowledge translation to develop understanding of the Developmental Origins of Health and Disease (DOHaD) within the community offers the potential to encourage informed diet and lifestyle choices supporting reduction of NCD risk in current and future generations. Many women do not make sustained dietary change before or during pregnancy, therefore appropriate nutritional behaviours need to be established prior to adulthood. This makes adolescence an appropriate stage for interventions to establish suitable dietary and lifestyle behaviours. Therefore, we engaged adolescents in a school-based educational intervention, and assessed the value of this in development of understanding of DOHaD concepts to support behaviour change that could lead to NCD risk reduction in the next generation. Modules of course work were written for 11–14 year olds and trialled in nine schools. Matched pre- and post-intervention questionnaire responses from 238 students and 99 parents, and post-intervention interviews evaluated the intervention. Understanding of a link between maternal diet during pregnancy and the health of the foetus in adulthood increased from 46% to 76% following intervention. Post-intervention evidence suggests the programme facilitated discussion of diet, lifestyle and DOHaD concepts in most families. The intervention was effective in improving understanding of DOHaD concepts and in some cases led to appropriate behaviour change. However, the sustainability of these changes remains to be determined through on-going evaluation of attitudes and behaviour within this cohort.
The risk of developing cardiovascular diseases is known to begin before birth and the impact of the intrauterine environment on subsequent adult health is currently being investigated from many quarters. Following our studies demonstrating the impact of hypoxia in utero and consequent intrauterine growth restriction (IUGR) on the rat cardiovascular system, we hypothesized that changes extend throughout the vasculature and alter function of the renal artery. In addition, we hypothesized that hypoxia induces renal senescence as a potential mediator of altered vascular function. We demonstrated that IUGR females had decreased responses to the adrenergic agonist phenylephrine (PE; pEC50 6.50 ± 0.05 control v. 6.17 ± 0.09 IUGR, P < 0.05) and the endothelium-dependent vasodilator methylcholine (MCh; Emax 89.8 ± 7.0% control v. 41.0 ± 6.5% IUGR, P < 0.001). In IUGR females, this was characterised by increased basal nitric oxide (NO) modulation of vasoconstriction (PE pEC50 6.17 ± 0.09 IUGR v. 6.42 ± 0.08 in the presence of the NO synthase inhibitor N-nitro-l-arginine methyl ester hydrochloride (l-NAME; P < 0.01) but decreased activated NO modulation (no change in MCh responses in the presence of l-NAME), respectively. In contrast, IUGR males had no changes in PE or MCh responses but demonstrated increased basal NO (PE pEC50 6.29 ± 0.06 IUGR v. 6.42 ± 0.12 plus l-NAME, P < 0.01) and activated NO (Emax 37.8 ± 9.4% control v. −0.8 ± 13.0% plus l-NAME, P < 0.05) modulation. No significant changes were found in gross kidney morphology, proteinuria or markers of cellular senescence in either sex. In summary, renal vascular function was altered by hypoxia in utero in a sex-dependent manner but was unlikely to be mediated by premature renal senescence.
We have previously shown that adult rat offspring born intrauterine growth restricted (IUGR) as a result of a prenatal hypoxic insult exhibit several cardiovascular characteristics that are compatible with common manifestations of chronic iron toxicity. As hypoxia is one of the major regulators of iron absorption and metabolism, we hypothesized that hypoxia-induced IUGR offspring will have long-term changes in their ability to regulate iron metabolism leading to myocardial iron deposition and induction of myocardial oxidative stress. Pregnant Sprague Dawley rats were randomized to control (n = 8) or maternal hypoxia (11.5% oxygen; n = 8) during the last 6 days of pregnancy. At birth, litters were reduced to eight pups (four male and four female). At 4 or 12 months of age, offspring were euthanatized and samples (blood and myocardium) were collected. In only the male offspring, IUGR and aging were associated with an increase in myocardial markers of oxidative stress such as oxidized/reduced glutathione ratio and malondialdehyde. Aged male IUGR offspring also exhibited interstitial myocardial remodeling characterized by myocyte loss and disrupted extracellular matrix.Contrary to our hypothesis, however, neither IUGR nor aging were associated with changes in any systemic or local markers of iron metabolism. Our results suggest that hypoxic insults leading to IUGR produce long-term effects on the levels of oxidative stress and connective tissue distribution in the myocardium of male but not female offspring.
A low-carbohydrate, high-protein (LCHP) diet is often recommended for the prevention and management of diabetes in cats; however, the effect of macronutrient composition on insulin sensitivity and energetic efficiency for weight gain is not known. The present study compared the effect in adult cats (n 32) of feeding a LCHP (23 and 47 % metabolisable energy (ME)) and a high-carbohydrate, low-protein (HCLP) diet (51 and 21 % ME) on fasting and postprandial glucose and insulin concentrations, and on insulin sensitivity. Tests were done in the 4th week of maintenance feeding and after 8 weeks of ad libitum feeding, when weight gain and energetic efficiency of each diet were also measured. When fed at maintenance energy, the HCLP diet resulted in higher postprandial glucose and insulin concentrations. When fed ad libitum, the LCHP diet resulted in greater weight gain (P < 0·01), and was associated with higher energetic efficiency. Overweight cats eating the LCHP diet had similar postprandial glucose concentrations to lean cats eating the HCLP diet. Insulin sensitivity was not different between the diets when cats were lean or overweight, but glucose effectiveness was higher after weight gain in cats fed the HCLP diet. According to the present results, LCHP diets fed at maintenance requirements might benefit cats with multiple risk factors for developing diabetes. However, ad libitum feeding of LCHP diets is not recommended as they have higher energetic efficiency and result in greater weight gain.
This study aimed to identify risk factors for dogs becoming rectal carriers of multidrug-resistant (MDR) Escherichia coli while hospitalized in a veterinary teaching hospital. Exposures to potential risk factors, including treatments, hospitalization, and interventions during a 42-day pre-admission period and hospitalization variables, were assessed for 90 cases and 93 controls in a retrospective, risk-based, case-control study. On multivariable analyses, hospitalization for >6 days [odds ratio (OR) 2·91–8·00], treatment with cephalosporins prior to admission (OR 5·04, 95% CI 1·25–20·27), treatment with cephalosporins for >1 day (OR 5·18, 95% CI 1·86–14·41), and treatment with metronidazole (OR 7·17, 95% CI 1·01–50·79) while hospitalized were associated with increased risk of rectal carriage of MDR E. coli during hospitalization. The majority of rectal isolates obtained during the study period conformed to MDR E. coli clonal groups previously obtained from extraintestinal infections. These results can assist the development of improved infection control guidelines for the management of dogs in veterinary hospitals to prevent the occurrence of nosocomial clinical infections.
Proton radiography using laser-driven sources has been developed as a diagnostic since the beginning of the decade, and applied successfully to a range of experimental situations. Multi-MeV protons driven from thin foils via the Target Normal Sheath Acceleration mechanism, offer, under optimal conditions, the possibility of probing laser-plasma interactions, and detecting electric and magnetic fields as well as plasma density gradients with ~ps temporal resolution and ~ 5–10 µm spatial resolution. In view of these advantages, the use of proton radiography as a diagnostic in experiments of relevance to Inertial Confinement Fusion is currently considered in the main fusion laboratories. This paper will discuss recent advances in the application of laser-driven radiography to experiments of relevance to Inertial Confinement Fusion. In particular we will discuss radiography of hohlraum and gasbag targets following the interaction of intense ns pulses. These experiments were carried out at the HELEN laser facility at AWE (UK), and proved the suitability of this diagnostic for studying, with unprecedented detail, laser-plasma interaction mechanisms of high relevance to Inertial Confinement Fusion. Non-linear solitary structures of relevance to space physics, namely phase space electron holes, have also been highlighted by the measurements. These measurements are discussed and compared to existing models.
This study aimed to identify risk factors for intestinal colonization with multidrug-resistant (MDR) E. coli in dogs on admission to a veterinary teaching hospital. Exposures to potential risk factors, including prior treatments, hospitalizations and interventions during the 42 days prior to admission were assessed for 82 case admissions and 82 time-matched controls in a retrospective prevalence-based case-control study of 20 months duration. On multivariable analyses, risk of MDR E. coli colonization on admission was increased with prior hospitalization for 4–7 days and >7 days relative to shorter periods, and in dogs that had prior diagnostic imaging techniques. Univariable analyses indicated that risk was increased following prior treatment with several antimicrobial agents. However, on multivariable analysis, administration of fluoroquinolones was associated with increased risk but risk did not appear to increase following administration of other antimicrobials. These results can inform management of canine patients and infection control procedures to mitigate the risk of clinical disease due to MDR bacteria in hospitalized dogs.
To describe services used by children with epilepsy seen by a liaison psychiatry team in Scotland and to examine existing guidance. Case notes of all patients with epilepsy were systematically reviewed to determine service involvement.
The majority of patients attended joint psychiatry and neurology clinics. Scottish Intercollegiate Guidelines Network (SIGN) recommendations for the psychosocial management of children with epilepsy were met. Most patients were assessed by a clinical psychologist and received educational psychology input, individual and family treatment approaches. Half had social work involvement.
A liaison model is presented for the management of children with more complex epilepsy and psychiatric disorders.