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Objective: To determine if clinical evaluations of poststroke arm function correspond to everyday motor performance indexed by arm accelerometers. Design: Cross-sectional study analyzing baseline data from a larger trial (NCT02665052). Setting: Outpatient research center. Participants: Community-dwelling adults (N=20) with chronic arm motor deficits (stroke≥6mo). Intervention: A total of 72 hours of home wrist-worn accelerometry during normal routine. Main Outcome Measures: Clinical evaluations included the Fugl-Meyer Assessment (FMA), Action Research Arm Test (ARAT), Wolf Motor Function Test (WMFT), and 2 self-assessments: the Motor Activity Log (MAL) and hand motor subscale of the Stroke Impact Scale (SIS). Accelerometer-derived variables included quantifications of movement intensity (magnitude) and duration of arm use. Results: Participants had moderate arm impairment (FMA, 36.1±9.4). The accelerometer-derived mean magnitude ratio correlated significantly with the FMA (ρ=0.60, P

Objective: To demonstrate the feasibility of algorithmic prediction using a model of baseline arm movement, genetic factors, demographic characteristics, and multimodal assessment of the structure and function of motor pathways. To identify prognostic factors and the biological substrate for reductions in arm impairment in response to repetitive task practice. Design: This prospective single-group interventional study seeks to predict response to a repetitive task practice program using an intent-to-treat paradigm. Response is measured as a change of ≥5 points on the Upper Extremity Fugl-Meyer from baseline to final evaluation (at the end of training). Setting: General community. Participants: Anticipated enrollment of community-dwelling adults with chronic stroke (N=96; onset≥6mo) and moderate to severe residual hemiparesis of the upper limb as defined by a score of 10-45 points on the Upper Extremity Fugl-Meyer. Intervention: The intervention is a form of repetitive task practice using a combination of robot-assisted therapy coupled with functional arm use in real-world tasks administered over 12 weeks. Main Outcome Measures: Upper Extremity Fugl-Meyer Assessment (primary outcome), Wolf Motor Function Test, Action Research Arm Test, Stroke Impact Scale, questionnaires on pain and expectancy, magnetic resonance imaging, transcranial magnetic stimulation, arm kinematics, accelerometry, and a saliva sample for genetic testing. Results: Methods for this trial are outlined, and an illustration of interindividual variability is provided by example of 2 participants who present similarly at baseline but achieve markedly different outcomes. Conclusion: This article presents the design, methodology, and rationale of an ongoing study to develop a predictive model of response to a standardized therapy for stroke survivors with chronic hemiparesis. Applying concepts from precision medicine to neurorehabilitation is practicable and needed to establish realistic rehabilitation goals and to effectively allocate resources. Keywords: Magnetic resonance imaging, Prognosis, Rehabilitation, Stroke, Transcranial magnetic stimulation

Background: Bronchopulmonary dysplasia (BPD) is a significant contributor to morbidity and death in infants who are born premature. Male sex is an independent risk factor for the development of BPD. However, whether male sex is associated with adverse outcomes that occur after formal diagnosis of severe BPD prior to hospital discharge remains unclear., Research Question: Is male sex associated with a higher risk of adverse outcomes in infants with established severe BPD?, Study Design and Methods: A retrospective, multicenter cohort study of infants enrolled in the BPD Collaborative Registry from January 1, 2015, to June 29, 2022, was performed. Demographics, clinical characteristics, and outcomes were stratified by sex (ie, male vs female). Regression modeling was used to estimate the association of sex with the primary composite outcome of death or tracheostomy at hospital discharge., Results: We identified 1,156 infants with severe BPD, defined at 36 weeks postmenstrual age by the National Institutes of Health 2001 consensus definition. The cohort was predominantly male (59% male infants, 41% female infants). However, rates of mechanical ventilation at 36 weeks postmenstrual age (ie, type 2 severe BPD) did not differ by sex. Overall mortality rates within the cohort were low (male infants, 5.3%; female infants, 3.6%). The OR of death or tracheostomy for male-to-female infants was 1.0 (95% CI, 0.7-1.5)., Interpretation: Our results lead us to speculate that, although sex is an important variable that contributes to the development and pathogenesis of severe BPD, it does not appear to be associated with adverse outcomes in this cohort of infants with established disease. The surprising results raise important questions surrounding the temporal role of biological sex in the development of severe BPD and its progression during the neonatal ICU stay. As we explore the phenotypes and endotypes of BPD, it is imperative to consider how sex modulates the disease from birth through hospital discharge., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2024. Published by Elsevier Inc.)

Study Objective: Little is known of the goals of care of older people living with frailty when they access urgent care. Equally whether these goals are attained from a patient and carer perspective is often unclear. This qualitative study examined the views of older people living with frailty and their families in relation to specific episodes of urgent care, what they wanted to achieve and whether those goals were attained., Methods: Semi-structured interviews with older people living with frailty and their families between Jan and July 2019. Patient and carer participants were recruited in three hospitals in England and interviewed following the urgent care episode. Interviews were audio-recorded, transcribed verbatim and analysed following the principles of the Framework approach. Results were validated by an older people's involvement group., Results: Forty participants were interviewed either alone or jointly (24 patients and 16 carers), describing episodes of urgent care which started in ED for 28 patients. The goals of care for participants accessing emergency care were that their medical problem be diagnosed and resolved; information about tests and treatment be given to them and their relatives; they receive an appropriate well-planned discharge to their own home with support where needed and without readmission or re-attendance at ED; and that they retain mobility, function and normal activities. Participants perceived that many of these goals of care were not attained., Conclusions: Older people living with frailty have heterogeneous urgent care goals which require individual ascertainment. Identifying these goals of care early could result in improved attainment through person-centred care., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Stress in pregnancy is associated with adverse outcomes in offspring, and developmental programming is a potential mechanism. We have previously shown that depression in pregnancy is a valid and clearly defined stress paradigm, and both maternal antenatal and offspring stress-related biology is affected. This study aims to clarify whether maternal biology in pregnancy and offspring outcomes can also be influenced by a history of a prior depression, in the absence of depression in pregnancy. Our primary hypothesis is that, similarly to women with depression in pregnancy, women with a history of depression but who are not depressed in pregnancy will have increased cortisol secretion and markers of immune system function, and that their offspring will have poorer neuro-developmental competencies and increased cortisol stress response., Methods: A prospective longitudinal design was used in 59 healthy controls and 25 women with a past history of depression who were not depressed in pregnancy, named as 'history-only', and their offspring. Maternal antenatal stress-related biology (cortisol and markers of immune system function) and offspring outcomes (gestational age at birth, neonatal neurobehaviour (Neonatal Behavioural Assessment Scale, NBAS), cortisol stress response and basal cortisol at 2 and 12 months) and cognitive, language and motor development (Bayley Scales of Infant and Toddler Development (BSID)) were measured., Results: Compared with healthy pregnant women, those with a history of depression who remain free of depression in pregnancy exhibit increased markers of immune system function in pregnancy: IL-8 (d = 0.63, p = 0.030), VEGF (d = 0.40, p = 0.008) and MCP-1 (d = 0.61, p = 0.002) and have neonates with lower neurobehavioural scores in most areas, reaching statistical significance in thesocial-interactive (d = 1.26, p = 0.015) cluster. However, there were no differences in maternal or offspring HPA axis function or in infant development at 12 months., Conclusion: Our study indicates that pregnant women with a history of depression have increased markers of immune system function, and their offspring show behavioural alterations that may be the effects of in utero programming, epigenetic factors or genetic predisposition., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Personal protective equipment (PPE) compliance is important to reduce the rate of transmission of virulent pathogens to health care workers. Medical officer compliance with PPE protocol for COVID-19 was audited in a regional hospital in Australia early in the pandemic response., Methods: Compliance was assessed based on the order and technique of donning and doffing PPE, with medical officers from multiple departments and levels of seniority audited., Results: Average compliance from all participants was 58.61% with donning and 68.84% with doffing., Conclusion: Medical Officer compliance with PPE donning and doffing was poor and additional training was required., Competing Interests: Conflict of interest There are no conflicts of interest to be declared., (Crown Copyright © 2021. Published by Elsevier B.V. All rights reserved.)

The objective of the present study was to estimate genetic parameters for four organoleptic traits in beef meat, namely tenderness, juiciness, flavour and chewiness using data from 5380 young crossbred progeny of 748 different sires. As well as using the mean animal sensory score across all panellists for a given trait, other aggregate functions such as the median and modal values were also investigated. The heritability (SE) of mean tenderness, juiciness, flavour and chewiness was 0.16 (0.04), 0.14 (0.04), 0.11 (0.03) and 0.21 (0.06), respectively; heritability estimates for the other aggregate values of these traits were generally lower. All genetic correlations between tenderness, juiciness and flavour were positive (0.52 to 0.68) while the genetic correlations between these three traits with chewiness were all negative varying from -0.95 to -0.48. Weak genetic correlations (≤|0.16|) were evident between the sensory traits and all of carcass weight, conformation and subcutaneous fat cover., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The objective was to determine the factors associated with meat tenderness, juiciness, flavour and chewiness in 4791 growing crossbred cattle. Meat quality of bulls was inferior to that of both steers and heifers with little difference between the latter two genders. Angus, Hereford and Belgian Blues had the most tender meat with the Simmental being the toughest albeit the difference was, on average, only 5%. Moderate to strong correlations (r ≥ |0.43|) existed among tenderness, juiciness and flavour although some of the correlations differed by animal gender. Correlations between chewiness and tenderness in the different genders varied from -0.81 to -0.74 while the correlations between chewiness and the other sensory traits varied from -0.54 to -0.09. The (partial) correlations between each of the four sensory metrics and all of carcass weight, carcass conformation and carcass fat score were ≤|0.09| with most not being different from zero. Correlations between the sensory traits with growth rate, muscle depth, feed intake and efficiency were all ≤|0.08| and mostly not different from zero., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The objective of the present study was to quantify, using simulated data, the impact on estimated heritability of varying the number of panellists and their inter-correlations using meat sensory tenderness in cattle as an example. Estimated parameters from actual sensory-based tenderness scores from 9 individual panellists on 1252 beef cattle were used to parameterise the simulation. A single "tenderness score" for each of 10 panellists was simulated for 15,000 cattle. Heritability estimates were calculated for each of the 10 panellists individually as well as the mean score per animal for all n combinations of panellists. Heritability estimates improved with increasing number of panellists in line with expectations from a deterministic equation. The increase in heritability was due to a reduction in the residual variance, albeit the rate of reduction in residual variance declined with each additional panellist included in the calculated mean tenderness score. Results highlight the importance of reporting the number of panellist scores per animal as well as their inter-correlations in sensory-based studies., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Older people are increasing users of health care globally. We aimed to establish whether older people with characteristics of frailty and who are at risk of adverse health-care outcomes could be identified using routinely collected data., Methods: A three-step approach was used to develop and validate a Hospital Frailty Risk Score from International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnostic codes. First, we carried out a cluster analysis to identify a group of older people (≥75 years) admitted to hospital who had high resource use and diagnoses associated with frailty. Second, we created a Hospital Frailty Risk Score based on ICD-10 codes that characterised this group. Third, in separate cohorts, we tested how well the score predicted adverse outcomes and whether it identified similar groups as other frailty tools., Findings: In the development cohort (n=22 139), older people with frailty diagnoses formed a distinct group and had higher non-elective hospital use (33·6 bed-days over 2 years compared with 23·0 bed-days for the group with the next highest number of bed-days). In the national validation cohort (n=1 013 590), compared with the 429 762 (42·4%) patients with the lowest risk scores, the 202 718 (20·0%) patients with the highest Hospital Frailty Risk Scores had increased odds of 30-day mortality (odds ratio 1·71, 95% CI 1·68-1·75), long hospital stay (6·03, 5·92-6·10), and 30-day readmission (1·48, 1·46-1·50). The c statistics (ie, model discrimination) between individuals for these three outcomes were 0·60, 0·68, and 0·56, respectively. The Hospital Frailty Risk Score showed fair overlap with dichotomised Fried and Rockwood scales (kappa scores 0·22, 95% CI 0·15-0·30 and 0·30, 0·22-0·38, respectively) and moderate agreement with the Rockwood Frailty Index (Pearson's correlation coefficient 0·41, 95% CI 0·38-0·47)., Interpretation: The Hospital Frailty Risk Score provides hospitals and health systems with a low-cost, systematic way to screen for frailty and identify a group of patients who are at greater risk of adverse outcomes and for whom a frailty-attuned approach might be useful., Funding: National Institute for Health Research., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The contribution of animal breeding to changes in animal performance is well documented across a range of species. Once genetic variation in a trait exists, then breeding to improve the characteristics of that trait is possible, if so desired. Considerable genetic variation exists in a range of meat quality attributes across a range of species. The genetic variation that exists for meat quality is as large as observed for most performance traits; thus, within a well-structured breeding program, rapid genetic gain for meat quality could be possible. The rate of genetic gain can be augmented through the integration of DNA-based technologies into the breeding program; such DNA-based technologies should, however, be based on thousands of DNA markers dispersed across the entire genome. Genetic and genomic technologies can also have beneficial impact outside the farm gate as a tool to segregate carcasses or meat cuts based on expected meat quality features., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: The range and magnitude of potential benefits and harms of antihypertensive treatment in people with dementia has not been previously established., Methods: A scoping review to identify potential domains of benefits and harms of antihypertensive therapy in people with dementia was undertaken. Systematic reviews of these domains were undertaken to examine the magnitude of the benefits or harms., Results: Potential outcome domains identified in the 155 papers in the scoping review were cardiovascular events, falls, fractures and syncope, depression, orthostatic hypotension, behavioral disturbances, polypharmacy risks, kidney problems, sleep problems, interactions with cholinesterase inhibitors, and pain. The systematic reviews across these domains identified relatively few studies done in people with dementia, and no convincing evidence of safety, benefit, or harm across any of them., Discussion: Given the lack of firm evidence of benefits or harm from antihypertensive therapy in people with dementia and the weak evidence for benefits in people over 80 years of age, the current presumption that the favorable evidence drawn from the treatment of nondemented people should be extrapolated to those with dementia is contentious. There is sufficient evidence to warrant particular caution and further research into treatment in this group of patients., (Copyright © 2014 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: No previous longitudinal study has examined the impact of comorbid maternal personality disorder (PD) and depression on child development. We set out to examine whether maternal PD and depression assessed at 2 months post partum would be independently associated with adverse developmental outcomes at 18 months of age., Method: Women were recruited into the study shortly after delivery and screened for depression and PD. Those meeting criteria for depression, PD, or both conditions, were selected for assessment at 2 months post partum, together with a comparison group with neither condition (total sample, N = 200). Assessments of cognitive, social and emotional development were conducted with their children at 18 months of age., Results: Maternal postpartum depression and PD were both associated with higher levels of dysregulated infant behavior. There was a significant interaction between depression and PD in the model of dysregulated behavior and the detrimental effects of maternal depression and PD were evident only among mothers with both conditions. Maternal depression was independently associated with impaired infant cognitive scores and higher levels of internalizing behavior., Conclusions: Future studies of the effects of maternal depression should also take into account the effects of comorbid maternal PD. Health professionals need to be aware of the possible co-occurrence of PD among mothers presenting with postnatal depression and that mothers with these co-occurring disorders are likely to require greater support., (Copyright © 2012 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: To our knowledge, changes in steroid metabolism in subjects with anorexia nervosa (AN) after weight gain have not been elucidated., Objective: We characterized urinary steroid excretion and metabolism in AN patients and investigated the effects of refeeding., Design: In an intervention study, we recruited 7 women with life-threatening weight loss upon admission and after a median [interquartile range (IQR)] of 95 d (88-125 d) of intensive refeeding; 15 age-matched women were recruited as control subjects. The major urinary metabolites were quantified in 24-h collections by capillary gas chromatography. A single examiner measured weights, heights, and skinfold thicknesses., Results: The median (IQR) age of patients was 24 y (21-26 y), and the duration of AN was 4.0 y (3.3-8.0 y). Body mass index (BMI; in kg/m(2)) increased from 12.8 (12.7-13.1) to 18.6 (18.0-19.6) after refeeding (P < 0.0001). Steroid values [median pre-, post-refeeding (P value)] were as follows: androgen metabolites [472, 1017 μg/24 h (0.93)], cortisol metabolites [1960, 3912 μg/24 h (0.60)], and ratios of androsterone (5α)/etiocholanolone (5β) [0.28, 0.63 (<0.001)], 5α-/5β-tetrahydrocortisol [0.20, 0.48 (0.02)], tetrahydrocortisols/tetrahydrocortisone [0.87, 0.61 (0.09)], 20-hydroxy-/20-oxocortisol metabolites [0.29, 0.47 (0.01)], and 20α-/20β-reduced cortisol metabolites [1.18, 1.89 (≥1.00)]. BMI change was positively correlated with 5α-/5β-tetrahydrocortisol (r = 0.95, P < 0.001). Before refeeding, the following metabolites were lower in patients than in control subjects: androsterone, 5α-tetrahydrocortisol, α-cortolone and α-cortol, 5α-/5β-tetrahydrocortisol, androsterone/etiocholanolone, and 20-hydroxy/20-oxocortisol (all P < 0.05). After refeeding, all steroid metabolites in patients were at concentrations that were comparable with those in control subjects., Conclusions: Significant changes in urine steroid-metabolite excretion occurred upon starvation, which were reversed upon refeeding. For cortisol, there were decreases in 5α-/5β-tetrahydrocortisol and 20-hydroxy-/20-oxometabolites; for androgen, there was a decrease in androsterone/etiocholanolone.

The use of unlicensed and off-label medicines in neonates in intensive care is common and widespread. Up to 93% of babies receive at least one unlicensed or off-label medicine during their stay in intensive care. Such practice is an essential part of their care and should be done based on the best evidence available. However, problems arise - on an every-day basis - because of the lack of appropriate information and licensed medicine formulations for neonates. These problems include the selection of appropriate medicine and dose, administration and the increased risk of medication errors. Initiatives to improve the situation are underway in the US and are proposed in Europe. However, more urgent action is required to stop these babies continuing to be deprived of their basic human rights to safe, effective and high-quality therapy.

Background: The need to use unlicensed and off label drugs in children due to the lack of suitable, licensed formulations with appropriate prescribing information creates many problems on an everyday basis for healthcare professionals, carers and children., Patients and Methods: This prospective study was designed to examine the incidence and nature of unlicensed and off label prescribing, in paediatric oncology patients with acute lymphoblastic leukaemia and other malignancies. Inpatient and outpatient prescriptions were analysed for a 4-week period., Results: All patients received at least one unlicensed or off label drug. Fifty-five per cent of prescriptions were licensed, 19% were unlicensed and 26% were licensed drugs used in an off label manner. Unlicensed preparations were used in 40% of prescriptions for cytotoxic agents, due to a lack of commercially available formulations suitable for the paediatric patient. These drugs included mercaptopurine and methotrexate which have been used in the treatment of paediatric leukaemia for many years, their efficacy having been demonstrated by on-going Medical Research Council trials., Conclusions: It is disappointing that drugs, which are the mainstay of therapy for paediatric leukaemia and other malignancies, are unavailable in appropriate licensed formulations to facilitate their administration to children. This needs to be urgently addressed.

Infant crying, and parental concern about unexplained crying, peak when infants are around 6 weeks of age. Diary measures of amounts of time infants spent crying, sleeping, waking-settled and feeding at 6 weeks were obtained in three samples: a group of moderate criers (N = 45), a group with an evening crying peak (N = 33) and a group whose fuss/crying exceeded 3 h per day (persistent criers, N = 54). Substantial negative correlations between amounts of fuss/crying and sleeping, but few associations between fuss/crying and waking or feeding, were found. The persistent criers slept an average of 77 min per 24 h less than the moderate criers. The clearest group differences were in the daytime and all three groups showed evidence of a diurnal organisation in their behaviour. Persistent crying at 6 weeks is associated with a sleeping deficit.

Fractionation of rat liver by homogenization and differential centrifugation revealed that only about 83% of the transglutaminase activity in the tissue is in a soluble form, and that the remainder is associated with the particulate fraction. This latter activity remained with the membranes even after they were extensively washed to remove 99% of such soluble enzymes as lactate dehydrogenase and aldolase. Subsequent fractionation of the membranes by isopycnic density gradient centrifugation in sucrose resulted in a single band of transglutaminase activity at a density of 1.194 g/cm3. This activity was coincident with the major band of plasma membranes, which was identified by its content of 5'-nucleotidase, alkaline phosphodiesterase I, alkaline phosphatase and leucine aminopeptidase activities. After treatment with digitonin and fractionation on sucrose gradients, the transglutaminase activity and the plasma membrane marker enzyme activities were found at a new density of 1.210 g/cm3, while the enzyme markers for the other membrane fractions remained unchanged. From these data, we conclude that approximately 17% of the transglutaminase activity in rat liver is specifically associated with the plasma membranes.