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This Research Reflection provides an overview of three interrelated topics: (i) lameness in dairy cows, demonstrating the underpinning importance of the condition, (ii) dairy farmer detection, diagnosis and treatment of lameness and associated foot lesions as well as dairy farmer perceptions towards the condition and (iii) lameness detection technologies, and their potential application on farm to automate the detection of lameness in commercial dairy herds. The presented literature clearly demonstrates that lameness is a major health issue in dairy herds, compromising dairy cow welfare and productivity, and resulting in significant economic implications for dairy farmers. Despite this, dairy farmers fail to perceive lameness as a serious threat to their dairy business. This restricted perception of the importance of lameness may be a product of limited ability to detect lame cows. Many automated lameness detection technologies have been proposed to assist dairy farmers in managing their herds. However, limitations such as cost, performance and dairy farmer perception of the usefulness of these technologies, has lead to poor uptake. It can, therefore, be concluded that there is a need to more thoroughly evaluate the effectiveness of these technologies under on-farm conditions, potentially in the form of a demonstration farm network. This will allow generation of the necessary data required to show dairy farmers that these technologies are reliable and are economically rational for their dairy business.
Whole-grain wheat, in particular coloured varieties, may have health benefits in adults with chronic metabolic disease risk factors. Twenty-nine overweight and obese adults with chronic inflammation (high-sensitivity C-reactive protein) > 1·0 mg/l) replaced four daily servings of refined grain food products with bran-enriched purple or regular whole-wheat convenience bars (approximately 41–45 g fibre, daily) for 8 weeks in a randomised, single-blind parallel-arm study where body weight was maintained. Anthropometrics, blood markers of inflammation, oxidative stress, and lipaemia and metabolites of anthocyanins and phenolic acids were compared at days 1, 29 and 57 using repeated-measures ANOVA within groups and ANCOVA between groups at day 57, with day 1 as a covariate. A significant reduction in IL-6 and increase in adiponectin were observed within the purple wheat (PW) group. TNF-α was lowered in both groups and ferulic acid concentration increased in the regular wheat (RW) group. Comparing between wheats, only plasma TNF-α and glucose differed significantly (P < 0·05), that is, TNF-α and glucose decreased with RW and PW, respectively. Consumption of PW or RW products showed potential to improve plasma markers of inflammation and oxidative stress in participants with evidence of chronic inflammation, with modest differences observed based on type of wheat.
To assess the social disability of people with different psychiatric disorders.
Cross-site survey in five psychiatric hospitals (Dresden, Wrocław, London, Michalovce and Prague). Working-aged patients diagnosed (ICD-10) with schizophrenia and related disorders (F2), affective disorders (F3), anxiety disorders (F4), eating disorders (F5) and personality disorders (F6), were assessed at admission (n = 969) and 3 months after discharge (n = 753) using the Brief Psychiatric Rating Scale and the Groningen Social Disability Schedule. The main outcome measure was Interviewer-rated social disability.
During acute episodes patients with personality, eating and schizophrenic disorders functioned less effectively than those with affective or anxiety disorders. After controlling for age and severity of psychopathology, there was no significant effect of the diagnosis (during remission), sex, education and history of disorder on disability. Site, employment and partnership were significant factors for the level of social disability in both measure points.
Severity of psychopathological symptoms, not the diagnosis of a mental disorder, was the most significant factor in determining the level of social functioning, particularly during the remission period. Site, employment and partnership appeared as significant factors influencing the level of social disability.
Controlling norovirus transmission in units with immunocompromised patients is challenging. We present a cluster of norovirus cases that occurred on a stem-cell transplant unit and the prevention efforts that were implemented to limit the outbreak. Protocols developed to control this cluster may provide a model for other facilities.
Effective community engagement in T3–T4 research is widespread, however, similar stakeholder involvement is missing in T1–T2 research. As part of an effort to embed community stakeholders in T1–T2 research, an academic community partnered team conducted discussion groups with researchers to assess perspectives on (1) barriers/challenges to including community stakeholders in basic science, (2) skills/training required for stakeholders and researchers, and (3) potential benefits of these activities. Engaging community in basic science research was perceived as challenging but with exciting potential to incorporate “real-life” community health priorities into basic research, resulting in a new full-spectrum translational research model.
Birth weight and early growth have been associated with later blood pressure. However, not all studies consistently find a significant reduction in blood pressure with an increase in birth weight. In addition, the relative importance of birth weight and of other lifestyle and environmental factors is often overlooked and the association is rarely studied in adolescents. We investigated early life predictors, including birth weight, of adolescent blood pressure in the Gateshead Millennium Study (GMS). The GMS is a cohort of 1029 individuals born in 1999–2000 in Gateshead in Northern England. Throughout infancy and early childhood, detailed information were collected, including birth weight and measures of height and weight. Assessments of 491 returning participants at age 12 years included measures of body mass and blood pressure. Linear regression and path analysis were used to determine predictors and their relative importance on blood pressure. Birth weight was not directly associated with blood pressure at the age of 12. However, after adjustment for contemporaneous body mass index (BMI), an inverse association of standardized birth weight on systolic blood pressure was significant. The relative importance of birth weight on later systolic blood pressure was smaller than other contemporaneous body measures (height and BMI). There was no independent association of birth weight on blood pressure seen in this adolescent population. Contemporaneous body measures have an important role to play. Lifestyle factors that influence body mass or size, such as diet and physical activity, where interventions are directed at early prevention of hypertension should be targeted.
Epilepsy and mental illness have a bidirectional association. Psychiatrists are likely to encounter epilepsy as comorbidity. Seizures may present as mental illness. Equally, the management of psychiatric conditions has the potential to destabilise epilepsy. There is a need for structured epilepsy awareness and training amongst psychiatrists. This paper outlines key considerations around diagnosis, treatment and risk while suggesting practical recommendations.
We implemented a cross-sectional study in Tana River County, Kenya, a Rift Valley fever (RVF)-endemic area, to quantify the strength of association between RVF virus (RVFv) seroprevalences in livestock and humans, and their respective intra-cluster correlation coefficients (ICCs). The study involved 1932 livestock from 152 households and 552 humans from 170 households. Serum samples were collected and screened for anti-RVFv immunoglobulin G (IgG) antibodies using inhibition IgG enzyme-linked immunosorbent assay (ELISA). Data collected were analysed using generalised linear mixed effects models, with herd/household and village being fitted as random variables. The overall RVFv seroprevalences in livestock and humans were 25.41% (95% confidence interval (CI) 23.49–27.42%) and 21.20% (17.86–24.85%), respectively. The presence of at least one seropositive animal in a household was associated with an increased odds of exposure in people of 2.23 (95% CI 1.03–4.84). The ICCs associated with RVF virus seroprevalence in livestock were 0.30 (95% CI 0.19–0.44) and 0.22 (95% CI 0.12–0.38) within and between herds, respectively. These findings suggest that there is a greater variability of RVF virus exposure between than within herds. We discuss ways of using these ICC estimates in observational surveys for RVF in endemic areas and postulate that the design of the sentinel herd surveillance should consider patterns of RVF clustering to enhance its effectiveness as an early warning system for RVF epidemics.
Trait impulsivity is thought to play a key role in predicting behaviors on the externalizing spectrum, such as drug and alcohol use and aggression. Research suggests that impulsivity may not be a unitary construct, but rather multidimensional in nature with dimensions varying across self-report assessments and laboratory behavioral tasks. Few studies with large samples have included a range of impulsivity-related measures and assessed several externalizing behaviors to clarify the predictive validity of these assessments on important life outcomes.
Community adults (N = 1295) between the ages of 30 and 54 completed a multidimensional assessment of impulsivity-related traits (including 54 self-report scales of personality traits implicated in impulsive behaviors, and four behavioral tasks purporting to assess a construct similar to impulsivity) and reported on five externalizing behavioral outcomes (i.e. drug, alcohol, and cigarette use, and physical and verbal aggression). We ran an exploratory factor analysis on the trait scales, and then a structural equation model predicting the externalizing behaviors from the three higher-order personality factors (i.e. Disinhibition v. Constraint/Conscientiousness, Neuroticism/Negative Emotionality, and Extraversion/Positive Emotionality) and the four behavioral tasks.
Relations between the self-report factors and behavioral tasks were small or nonexistent. Associations between the self-report factors and the externalizing outcomes were generally medium to large, but relationships between the behavioral tasks and externalizing outcomes were either nonexistent or small.
These results partially replicate and extend recent meta-analytic findings reported by Sharma et al. (2014) to further clarify the predictive validity of impulsivity-related trait scales and laboratory behavioral tasks on externalizing behaviors.
Cryo-electron microscopy (cryo-EM) is a powerful tool for macromolecular to near-atomic resolution structure determination in the biological sciences. The specimen is maintained in a near-native environment within a thin film of vitreous ice and imaged in a transmission electron microscope. The images can then be processed by a number of computational methods to produce three-dimensional information. Recent advances in sample preparation, imaging, and data processing have led to tremendous growth in the field of cryo-EM by providing higher resolution structures and the ability to investigate macromolecules within the context of the cell. Here, we review developments in sample preparation methods and substrates, detectors, phase plates, and cryo-correlative light and electron microscopy that have contributed to this expansion. We also have included specific biological applications.
OBJECTIVES/SPECIFIC AIMS: The purpose of this study was to characterize the pharmacokinetics of phosphatidylethanol (PEth) 16:0/20:4 homolog in uncoagulated, human blood samples taken from 18 participants in a clinical laboratory setting after consumption of 2 doses of ethanol. METHODS/STUDY POPULATION: Male and female participants received either 0.4 or 0.8 g/kg oral doses of ethanol during a 15-minute period. Blood samples were collected before and throughout 6 hours immediately after alcohol administration, then after 2, 4, 7, 11, and 14 days of administration day. PEth 16:0/20:4 levels were quantified by liquid mass spectrometry. Breath ethanol concentrations were measure concurrently with each blood collection during the administration day, as well as transdermal ethanol concentrations monitored constantly before, during and after ethanol administration day. RESULTS/ANTICIPATED RESULTS: (1) Single doses of 0.4 and 0.8 g ethanol/kg produced proportional increases in BrAC and PEth 16:0/20:4 levels; (2) the increase of Peth 16:0/20:4 from base line to Cmax was less than either PEth 16:0/18:1 or PEth 16:0/18:2 during the 6-hour period after ethanol administration; (3) the mean rate of formation of PEth 16:0/20:4 was lower than those of the other 2 homologs; (4) the mean half-life of PEth 16:0/20:4 was 2.18 days, which was shorter than that of either PEth 16:0/18:1 and PEth 16:0/18:2, which were 6.80 and 6.62, respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: The results of this study further confirm that PEth homologs are a sensitive biomarker for ethanol consumption. The measurement of three PEth homologs appears to provide additional information about the level and time frame of drinking.
BACKGROUND: IGTS is a rare phenomenon of paradoxical germ cell tumor (GCT) growth during or following treatment despite normalization of tumor markers. We sought to evaluate the frequency, clinical characteristics and outcome of IGTS in patients in 21 North-American and Australian institutions. METHODS: Patients with IGTS diagnosed from 2000-2017 were retrospectively evaluated. RESULTS: Out of 739 GCT diagnoses, IGTS was identified in 33 patients (4.5%). IGTS occurred in 9/191 (4.7%) mixed-malignant GCTs, 4/22 (18.2%) immature teratomas (ITs), 3/472 (0.6%) germinomas/germinomas with mature teratoma, and in 17 secreting non-biopsied tumours. Median age at GCT diagnosis was 10.9 years (range 1.8-19.4). Male gender (84%) and pineal location (88%) predominated. Of 27 patients with elevated markers, median serum AFP and Beta-HCG were 70 ng/mL (range 9.2-932) and 44 IU/L (range 4.2-493), respectively. IGTS occurred at a median time of 2 months (range 0.5-32) from diagnosis, during chemotherapy in 85%, radiation in 3%, and after treatment completion in 12%. Surgical resection was attempted in all, leading to gross total resection in 76%. Most patients (79%) resumed GCT chemotherapy/radiation after surgery. At a median follow-up of 5.3 years (range 0.3-12), all but 2 patients are alive (1 succumbed to progressive disease, 1 to malignant transformation of GCT). CONCLUSION: IGTS occurred in less than 5% of patients with GCT and most commonly after initiation of chemotherapy. IGTS was more common in patients with IT-only on biopsy than with mixed-malignant GCT. Surgical resection is a principal treatment modality. Survival outcomes for patients who developed IGTS are favourable.
OBJECTIVES/SPECIFIC AIMS: Characterize the expression kinetics of HIV-1 Envelope and their relationship to virus production at the cellular level. METHODS/STUDY POPULATION: In vitro and ex vivo laboratory analyses. RESULTS/ANTICIPATED RESULTS: Initial studies addressing the kinetics of cell surface. Envelope (Env) expression reveal that Env expression to peaks on day 2 post infection. Next steps include a series of experiments to compare the kinetics of Env cell surface expression with broadly neutralizing antibody (bNAb)-mediated ADCC and the characterization of virus production kinetics in this same context. To be maximally effective, ADCC elimination of infected cells should occur before peak Env expression. DISCUSSION/SIGNIFICANCE OF IMPACT: Potent bNAbs to HIV-1 recognize vulnerable sites on the HIV-1 Envelope (Env) protein and are of great clinical interest due to their potential use in the prevention and treatment of HIV-1 infection. Their effectiveness depends not only on the neutralization of viral infectivity, but also on the elimination of productively infected cells via antibody-dependent cellular cytotoxicity (ADCC). On a cellular level, ADCC dynamics are determined by the timing and level of Env expression on the surface of HIV-infected cells. This study aims to delineate the expression kinetics of HIV-1 Envelope and their relationship to virus production. We expect that it will provide new insights into the utility of bNAb-mediated ADCC in treating and possibly curing HIV-1 infection; therefore results might have substantial impact on future HIV treatment strategies.
Improving compliance with hand hygiene is a cornerstone of infection prevention. However, data regarding practical methods for monitoring compliance are limited. We found that product use metrics have a moderate correlation with direct observation in ward settings and limited correlation in intensive care units.
Herbicide resistance, and in particular multiple-herbicide resistance, poses an ever-increasing threat to food security. A biotype of junglerice [Echinochloa colona (L.) Link] with resistance to four herbicides, imazamox, fenoxaprop-P-ethyl, quinclorac, and propanil, each representing a different mechanism of action, was identified in Sunflower County, MS. Dose responses were performed on the resistant biotype and a biotype sensitive to all four herbicides to determine the level of resistance. Application of a cytochrome P450 inhibitor, malathion, with the herbicides imazamox and quinclorac resulted in increased susceptibility in the resistant biotype. Differential gene expression analysis of resistant and sensitive plants revealed that 170 transcripts were upregulated in resistant plants relative to sensitive plants and 160 transcripts were upregulated in sensitive plants. In addition, 507 transcripts were only expressed in resistant plants and 562 only in sensitive plants. A subset of these transcripts were investigated further using quantitative PCR (qPCR) to compare gene expression in resistant plants with expression in additional sensitive biotypes. The qPCR analysis identified two transcripts, a kinase and a glutathione S-transferase that were significantly upregulated in resistant plants compared with the sensitive plants. A third transcript, encoding an F-box protein, was downregulated in the resistant plants relative to the sensitive plants. As no cytochrome P450s were differentially expressed between the resistant and sensitive plants, a single-nucleotide polymorphism analysis was performed, revealing several nonsynonymous point mutations of interest. These candidate genes will require further study to elucidate the resistance mechanisms present in the resistant biotype.
Water wave overwash of a step by small steepness, regular incident waves is analysed using a computational fluid dynamics (CFD) model and a mathematical model, in two spatial dimensions. The CFD model is based on the two-phase, incompressible Navier–Stokes equations, and the mathematical model is based on the coupled potential-flow and nonlinear shallow-water theories. The CFD model is shown to predict vortices, breaking and overturning in the region where overwash is generated, and that the overwash develops into fast-travelling bores. The mathematical model is shown to predict bore heights and velocities that agree with the CFD model, despite neglecting the complicated dynamics where the overwash is generated. Evidence is provided to explain the agreement in terms of the underlying agreement of mass and energy fluxes.
The history of Newcastle upon Tyne and its hinterland has tended to be dominated by the rise and, latterly, the decline of the coal industry. In the seventeenth and eighteenth centuries the local economy of Newcastle upon Tyne was being driven by this thriving industry, which was underpinned by the demand for coal from the rapidly growing metropolis of London, together with markets served by other east coast and foreign ports. By the eighteenth century Newcastle had become a bustling centre of trade and commerce as a consequence of the impact of the burgeoning coal trade upon the economy of the town and its surrounding communities. Unfortunately, this dominance of the coal industry in the local history of Newcastle has often obscured the detail of the economic and social consequences of this economic dynamism, which fostered the development of many other trade and business networks that extended far beyond the coal sector into many aspects of the more general trades of the town. As Newcastle became a flourishing port with a thriving community of merchants and tradesmen, this coal-driven economic momentum involved an expanding population and the development of an urban ‘middling class’. Among this community relative wealth and disposable spending power grew, with increasing expectations of an improved material quality of life fostering the development of a consumer demand for goods. This demand was expressed in terms of both the import of a wider range of more exotic foodstuffs and an increased availability of a wider range of quality soft furnishings and clothing. Newcastle thus participated in the ‘culture of consumption’ that was becoming a pronounced feature of the seventeenth and eighteenth centuries across much of north-western Europe. The consumption of goods has been the subject of extensive analysis by historians, relating the increased demand associated with consumption to the development of markets and altered patterns of sociability within the community. The course of these changes in consumption habits and regional culture in the north-east of England has been lucidly presented in a series of essays edited by Helen Berry and Jeremy Gregory in which a number of distinct features are highlighted, characterised in part by the local industrial and trading community, which was dominated by the coal trade.
Family-based strategies to reduce the risk of overweight in childhood are needed in the Caribbean.
To investigate the associations between parental characteristics and risk of overweight and explore possible mechanisms.
Data from a parenting intervention were analysed. Parental characteristics were obtained by questionnaire at enrolment. At 18 months, 501 infants (82.9% of cohort) had weight and length measured using standardized methods. The association of parents’ characteristics with risk of infant overweight was assessed using random-effects logistic regression. Four focus groups among mothers in Jamaica were conducted to explore mechanisms.
Overall, 20.6% of infants were ‘at risk of overweight’. Fathers were present in 52% of households. Fathers’ presence [OR (95% CI) 0.60 (0.37–0.96)] was associated with reduced risk of overweight independent of socioeconomic status. Mothers reported that fathers encouraged healthier practices.
Fathers may be important agents of change in intervention strategies to prevent childhood overweight.