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Clinical ethics consultants navigate dilemmas across patient care, public health, healthcare policy, and professional guidelines with issues spanning from the beginning to the end of life, complex discharges, employment of novel technologies, and visitation restrictions. The second edition relays the narratives of fraught, complex consultations through richly detailed cases exploring the ethical reasoning, professional issues, and the emotional aspects of these impossibly difficult scenarios. Describing the affective aspects of ethics consultations, authors highlight the lasting effects of these cases on their practices and reflect candidly on evolving professional practice as well as contemporary concerns and innovations, with attention to equity and inclusivity. Featuring many new chapters, cases are grouped together by theme to aid teaching, discussion, and professional growth. The book is intended for clinicians, bioethicists, and ethics committee members with an interest in the choices made in real-life medical dilemmas as well as the emotional cost to those working to improve the situations.
New technologies and disruptions related to Coronavirus disease-2019 have led to expansion of decentralized approaches to clinical trials. Remote tools and methods hold promise for increasing trial efficiency and reducing burdens and barriers by facilitating participation outside of traditional clinical settings and taking studies directly to participants. The Trial Innovation Network, established in 2016 by the National Center for Advancing Clinical and Translational Science to address critical roadblocks in clinical research and accelerate the translational research process, has consulted on over 400 research study proposals to date. Its recommendations for decentralized approaches have included eConsent, participant-informed study design, remote intervention, study task reminders, social media recruitment, and return of results for participants. Some clinical trial elements have worked well when decentralized, while others, including remote recruitment and patient monitoring, need further refinement and assessment to determine their value. Partially decentralized, or “hybrid” trials, offer a first step to optimizing remote methods. Decentralized processes demonstrate potential to improve urban-rural diversity, but their impact on inclusion of racially and ethnically marginalized populations requires further study. To optimize inclusive participation in decentralized clinical trials, efforts must be made to build trust among marginalized communities, and to ensure access to remote technology.
The incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure in shared patient rooms was low at our institution: 1.8 per 1,000 shared-room patient days. However, the secondary attack rate (21.6%) was comparable to that reported in household exposures. Lengthier exposures were associated with SARS-CoV-2 conversion. Hospitals should implement measures to decrease shared-room exposures.
The fundamental nature of turbulent density fluctuations in standard Wendelstein 7-X (W7-X) stellarator discharges is investigated experimentally via phase contrast imaging (PCI) in combination with gyrokinetic simulations with the code GENE. We find that density fluctuations are ion-temperature-gradient-driven and radially localised in the outer half of the plasma. It is shown that the line-integrated PCI measurements cover the right range of wavenumbers and a favourable toroidal and poloidal location to capture some of the strongest density fluctuations in W7-X. Due to the radial localisation of fluctuations, measured wavenumber–frequency spectra exhibit a dominant phase velocity, which can be related to the $\boldsymbol {E\times B}$ rotation velocity at the radial position of a well in the neoclassical radial electric field. The match is robust against variations of heating power and line-integrated density, which is partly due to the localisation of fluctuations and partly due to effects of the radial gradient in the $\boldsymbol {E\times B}$ velocity profile on the wavenumber–frequency spectrum. The latter effect is studied with a newly built synthetic PCI diagnostic and global gyrokinetic simulations with GENE-3D.
Schizophrenia (SZ) is associated with thalamic dysconnectivity. Compared to healthy controls (HCs), individuals with SZ have hyperconnectivity with sensory regions, and hypoconnectivity with cerebellar, thalamic, and prefrontal regions. Despite replication of this pattern in chronically ill individuals, less is known about when these abnormalities emerge in the illness course and if they are present prior to illness onset.
Methods
Resting-state functional magnetic resonance imaging data were collected from psychosis risk syndrome (PRS) youth (n = 45), early illness SZ (ESZ) (n = 74) patients, and HCs (n = 85). Age-adjusted functional connectivity, seeded from the thalamus, was compared among the groups.
Results
Significant effects of group were observed in left and right middle temporal regions, left and right superior temporal regions, left cerebellum, and bilateral thalamus. Compared to HCs, ESZ demonstrated hyperconnectivity to all temporal lobe regions and reduced connectivity with cerebellar, anterior cingulate, and thalamic regions. Compared to HCs, PRS demonstrated hyperconnectivity with the left and right middle temporal regions, and hypoconnectivity with the cerebellar and other thalamic regions. Compared to PRS participants, ESZ participants were hyperconnected to temporal regions, but did not differ from PRS in hypoconnectivity with cerebellar and thalamic regions. Thalamic dysconnectivity was unrelated to positive symptom severity in ESZ or PRS groups.
Conclusions
PRS individuals demonstrated an intermediate level of thalamic dysconnectivity, whereas ESZ showed a pattern consistent with prior observations in chronic samples. These cross-sectional findings suggest that thalamic dysconnectivity may occur prior to illness onset and become more pronounced in early illness stages.
White matter development during adolescents is crucial for a mature integration of neural networks in the brain. Autism spectrum condition (ASC), characterized by social and communication difficulties and rigid behaviour may interact with white matter development observed during adolescence. Changes in white matter development may link autistic symptoms to its genetic underpinnings and explain a 10-fold increase in susceptibility to ASC among siblings of individuals with ASC.
We used diffusion tensor imaging to study an association between age and white matter integrity measures, fractional anisotropy (FA) and mean diffusivity (MD), in adolescents with ASC, their siblings and age-matched healthy controls. Diffusion-weighted data were acquired with 64-direction protocol with 3mm slices and TR of 6600ms and tract-based spatial statistics analysis was performed.
The control subjects showed robust signs of increase in white matter integrity correlated with age. In contrast, individuals with ASC showed significantly lower negative correlation between MD and age in a broad area centred in the right superior longitudinal fasciculus (rSLF). When the three eigenvalues constituting a tensor ellipsoid were considered separately, siblings of individuals with ASC showed a diminished negative correlation between the second eigenvalue and age also centred in the rSLF.
Adolescents with ASC and their siblings experience alterations in white matter development in comparison to age-matched healthy controls, which are similar in direction yet different in scale for the two affected groups. The alterations are observed in the area associated with flexibility of behaviour and may explain both symptoms of ASC and increased susceptibility to ASC.
Autism Spectrum Disorders (ASDs) affect 1% of children and are associated with lifelong psychosocial impairments. The majority of children with ASD will experience co-occurring psychiatric disorders. In the UK, antipsychotics remain unlicensed for use in ASDs, however 10% of children with ASD receive antipsychotic treatment; the co-occurring disorders being targeted by these medications remains unclear.
Objectives
To examine rates of antipsychotic medication use and identify associated co-occurring disorders among children with ASD receiving psychiatric care.
Methods
The sample consisted of 2844 children aged 2 to 17 with a NHS clinician recorded ICD-10 diagnoses for ASD between 2008–2013. Clinical variables extracted from their anonymised electronic patient records included disorder severity, medication use, co-occurring ICD-10 diagnoses, family characteristics, demographics and antipsychotic use.
Results
Of the 2844 children (79% male), the majority (57%) had co-occurring psychiatric diagnoses. 313 (11%) received antipsychotic medication. The proportion of children aged 13 to 17 years and 6 to 12 years prescribed antipsychotics was 19% and 7% respectively. After controlling for socio-demographic factors, disorder severity, specialist treatment, inpatient duration, risk of self harm, violence to others, self injurious behaviour, maltreatment history, parental mental illness, caregiver anxiety, and neighbourhood deprivation, multivariate regression analysis revealed only hyperactivity disorders (O.R 1.94, 95%C.I. 1.32–2.86), psychotic disorders (O.R 5.12 95% C.I. 2.6–10.1), mood disorders (O.R 2.02, 95%C.I. 1.04–3.92) and intellectual disability (O.R 2.89 95% C.I. 1.89–4.71) were associated with anti-psychotic use.
Conclusions
The prescription of antipsychotic medications in this UK ASD clinical sample is strongly associated with specific co-occurring psychiatric disorders and intellectual disability.
Tear staining (TS) in the pig has been related to different stressors and may be a useful tool for assessing animal welfare on farm. The aim of the current study was to investigate TS across the finisher period and its possible relation to age, growth, sex and experimentally induced stressors. The study included 80 finisher pens divided between three batches. Within each batch, the pens either included pigs with docked or undocked tails, had straw provided (150 g/pig/day) or not and had a low (1.21 m2/pig, 11 pigs) or high stocking density (0.73 m2/pig, 18 pigs). Tear staining (scores 1 to 4; from smaller to larger tear stain area, respectively) and tail damage were scored on each individual pig three times per week over the 9-week study period, and the individual maximum TS score within each week was chosen for further analysis. Data were analysed using logistic regression separately for each of the four possible TS score levels. The TS scores 1 and 2 decreased with weeks into the study period and were negatively related to the average daily gain (ADG) of the pigs, whereas the TS score 4 increased with weeks into the study period and was positively related to ADG. None of the TS scores differed between females and castrated males, and neither straw provision nor lowering the stocking density affected the TS scores. However, the TS score 1 decreased the last week before an event of tail damage (at least one pig in the pen with a bleeding tail wound), whereas the TS score 4 increased. The results of the current study advocates for a relation between TS and the factors such as age, growth and stress in the pig, while no relation was found between TS and the environmental factors straw provision and lowered stocking density. The relations to age and growth are important to take into consideration if using TS as a welfare assessment measure in the pig in the future.
Loose farrowing pens have been considered as alternatives to crates to enhance sow welfare. A major concern with pen systems is often higher piglet pre-weaning mortality, especially due to crushing by the sow. An optimal management of light and mat surface temperature may promote greater piglet use of the creep, which has been associated with reduced piglet crushing. A total of 108 sows and their piglets were studied in sow welfare and piglet protection pens on a commercial piggery, across two replicates. Sows were randomly assigned to pens arranged within two creep treatments (bright creep: 300 lx v. dark creep: 4 lx), considering mat temperature as a covariate. Twelve sows and their litters in each treatment (24 in total) had their behaviour continuously recorded for 72-h postpartum (pp), and four focal piglets per litter were weighed on the first and third days pp. In situ behaviour observations were performed daily (from 0800 to 1700 h) on all sows and their litters, every 15 min over 72-h pp to record piglet time spent in the creep, latency to enter the creep for the first time, latency for the litter to remain in the creep for at least 10 min, and piglet and sow use of pen areas immediately in front of (A2) and farthest from the creep (A3). Piglets with access to bright creeps spent on average 7.2% more time (P<0.01) in the creeps than piglets in pens with Dark creeps. In addition, for each degree increase in mat temperature, piglets spent on average 2.1% more time (P<0.01) in the creep. Piglets in pens with bright creeps spent less time in A2 (P=0.04) and the least time in A3 (P=0.01). Light or mat temperature did not affect sow use of pen areas or piglet weight gain. Piglets with bright creeps tended (P=0.06) to take longer to enter the creep for the first time after birth, but the latency for 30.0% of the litter to remain clustered for 10 min tended (P=0.08) to be shorter in bright compared to dark creeps. Overall, piglet use of the creep increased with warm mat temperatures and brightness, which should be further investigated as potential strategies to promote piglet safety and reduce crushing in pen farrowing systems.
Landraces (including heritage varieties) are an important agrobiodiversity resource offering considerable value as a buffer against crop failures, as a crop for niche markets, and as a source of diversity for crop genetic improvement activities underpinning future food security. Home gardens are reservoirs of landrace diversity, but some of the accessions held in them are vulnerable or threatened with extinction. Those associated with seed saving networks have added security, for example, ca. 800 varieties are stored in the Heritage Seed Library (HSL) of Garden Organic, UK. In this study, Amplified Fragment Length Polymorphisms-based genetic analysis of accessions held in the HSL was used to (a) demonstrate the range of diversity in the collection, (b) characterize accessions to aid collection management and (c) promote broader use of the collection. In total, 171 accessions were included from six crops: Vicia faba L., Pisum sativum L., Daucus carota L., Cucumis sativus L., Lactuca sativa L. and Brassica oleracea L. var. acephala (DC.) Metzq. Average expected heterozygosity ranged from 0.18 to 0.28 in D. carota; 0.02–0.18 in P. sativum; 0.05–0.18 in L. sativa; 0.15–0.26 in B. oleracea var. acephala; 0.15–0.37 in C. sativus and 0.07–0.36 in V. faba. Genetic diversity and Fst values generally reflected the breeding system and cultivation history of the different crops. Comparisons of the diversity found in heritage varieties with that found in commercial varieties did not show a consistent pattern. Principal coordinates analysis and Unweighted Pair Group Method with Arithmetic Mean cluster analysis were used to identify four potential duplicate accession pairs.
During vocalization, efference copy/corollary discharge mechanisms suppress the auditory cortical response to self-generated sounds. Previously, we found attenuated vocalization-related auditory cortical suppression in psychosis and a similar trend in the psychosis risk syndrome. Here, we report data from the final sample of early illness schizophrenia patients (ESZ), individuals at clinical high risk for psychosis (CHR), and healthy controls (HC).
Methods
Event-related potentials (ERP) were recorded from ESZ (n = 84), CHR (n = 71), and HC (n = 103) participants during a vocalization paradigm. The N1 ERP component was elicited during production (Talk) and playback (Listen) of vocalization. Age effects on N1 suppression (Talk–Listen), Talk N1, and Listen N1 were compared across groups. N1 measures were adjusted for normal aging before testing for group differences.
Results
Both ESZ and CHR groups showed reduced Talk–Listen N1 suppression relative to HC, but did not differ from each other. Listen N1 was reduced in ESZ, but not in CHR, relative to HC. Deficient Talk–Listen N1 suppression was associated with greater unusual thought content in CHR individuals. N1 suppression increased with age in HC (12–36 years), and while CHR individuals showed a similar age-related increase, no such relationship was evident in ESZ.
Conclusions
Putative efference copy/corollary discharge-mediated auditory cortical suppression during vocalization is deficient in ESZ and precedes psychosis onset, particularly in CHR individuals with greater unusual thought content. Furthermore, this suppression increases from adolescence through early adulthood, likely reflecting the effects of normal brain maturation. This maturation effect is disrupted in ESZ, presumably due to countervailing illness effects.
Group housing of gestating sows benefits their welfare by allowing them freedom of movement and the opportunity for social interaction. However, social life could also bring disadvantages for individuals who receive direct aggression or are displaced from the feeder. The aim of this study was to investigate associations between social behaviour, body condition and live weight. Gestating sows (n=298) were investigated on a commercial farm. Sows were housed in mixed parity groups where two single space, ad libitum trough feeders served 12 animals. Sows were weighed, body condition scored and had their back fat layer measured at mixing, 4 weeks after insemination and again before farrowing. Social status was estimated based on the numbers of won and lost agonistic interactions at mixing and at the end of gestation. In addition, tear staining was scored before the farrowing and reproductive performance data were collected. With the aid of video recordings, 100 to 150 interactions per group were observed. Winning percentage at mixing and at the end of gestation were associated (P<0.05) and appeared relatively stable within individuals. Tear staining scores and litter sizes were not associated with winning percentage at the end of gestation. However, live weight, relative weight, body condition and back fat thickness were associated with winning percentage (P<0.05), giving heavier animals an advantage. Low winning percentage related to lower live weight gain, probably due to poorer success in competition for feed. Live weight within a mixed parity group could be used as a proxy measure for social status. Sows with low body condition score and submissive sows might need special attention with regard to group dynamics and housing to alleviate the effects of competition in group housing.
Schizophrenia (SZ) is a severe neuropsychiatric disorder associated with disrupted connectivity within the thalamic-cortico-cerebellar network. Resting-state functional connectivity studies have reported thalamic hypoconnectivity with the cerebellum and prefrontal cortex as well as thalamic hyperconnectivity with sensory cortical regions in SZ patients compared with healthy comparison participants (HCs). However, fundamental questions remain regarding the clinical significance of these connectivity abnormalities.
Method
Resting state seed-based functional connectivity was used to investigate thalamus to whole brain connectivity using multi-site data including 183 SZ patients and 178 matched HCs. Statistical significance was based on a voxel-level FWE-corrected height threshold of p < 0.001. The relationships between positive and negative symptoms of SZ and regions of the brain demonstrating group differences in thalamic connectivity were examined.
Results
HC and SZ participants both demonstrated widespread positive connectivity between the thalamus and cortical regions. Compared with HCs, SZ patients had reduced thalamic connectivity with bilateral cerebellum and anterior cingulate cortex. In contrast, SZ patients had greater thalamic connectivity with multiple sensory-motor regions, including bilateral pre- and post-central gyrus, middle/inferior occipital gyrus, and middle/superior temporal gyrus. Thalamus to middle temporal gyrus connectivity was positively correlated with hallucinations and delusions, while thalamus to cerebellar connectivity was negatively correlated with delusions and bizarre behavior.
Conclusions
Thalamic hyperconnectivity with sensory regions and hypoconnectivity with cerebellar regions in combination with their relationship to clinical features of SZ suggest that thalamic dysconnectivity may be a core neurobiological feature of SZ that underpins positive symptoms.
Phased Array Feed (PAF) technology is the next major advancement in radio astronomy in terms of combining high sensitivity and large field of view. The Focal L-band Array for the Green Bank Telescope (FLAG) is one of the most sensitive PAFs developed so far. It consists of 19 dual-polarization elements mounted on a prime focus dewar resulting in seven beams on the sky. Its unprecedented system temperature of ~17 K will lead to a 3 fold increase in pulsar survey speeds as compared to contemporary single pixel feeds. Early science observations were conducted in a recently concluded commissioning phase of the FLAG where we clearly demonstrated its science capabilities. We observed a selection of normal and millisecond pulsars and detected giant pulses from PSR B1937+21.
Faster eating rates are associated with increased energy intake, but little is known about the relationship between children’s eating rate, food intake and adiposity. We examined whether children who eat faster consume more energy and whether this is associated with higher weight status and adiposity. We hypothesised that eating rate mediates the relationship between child weight and ad libitum energy intake. Children (n 386) from the Growing Up in Singapore Towards Healthy Outcomes cohort participated in a video-recorded ad libitum lunch at 4·5 years to measure acute energy intake. Videos were coded for three eating-behaviours (bites, chews and swallows) to derive a measure of eating rate (g/min). BMI and anthropometric indices of adiposity were measured. A subset of children underwent MRI scanning (n 153) to measure abdominal subcutaneous and visceral adiposity. Children above/below the median eating rate were categorised as slower and faster eaters, and compared across body composition measures. There was a strong positive relationship between eating rate and energy intake (r 0·61, P<0·001) and a positive linear relationship between eating rate and children’s BMI status. Faster eaters consumed 75 % more energy content than slower eating children (Δ548 kJ (Δ131 kcal); 95 % CI 107·6, 154·4, P<0·001), and had higher whole-body (P<0·05) and subcutaneous abdominal adiposity (Δ118·3 cc; 95 % CI 24·0, 212·7, P=0·014). Mediation analysis showed that eating rate mediates the link between child weight and energy intake during a meal (b 13·59; 95 % CI 7·48, 21·83). Children who ate faster had higher energy intake, and this was associated with increased BMI z-score and adiposity.
Although repeatedly associated with white matter microstructural alterations, bipolar disorder (BD) has been relatively unexplored using complex network analysis. This method combines structural and diffusion magnetic resonance imaging (MRI) to model the brain as a network and evaluate its topological properties. A group of highly interconnected high-density structures, termed the ‘rich-club’, represents an important network for integration of brain functioning. This study aimed to assess structural and rich-club connectivity properties in BD through graph theory analyses.
Method
We obtained structural and diffusion MRI scans from 42 euthymic patients with BD type I and 43 age- and gender-matched healthy volunteers. Weighted fractional anisotropy connections mapped between cortical and subcortical structures defined the neuroanatomical networks. Next, we examined between-group differences in features of graph properties and sub-networks.
Results
Patients exhibited significantly reduced clustering coefficient and global efficiency, compared with controls globally and regionally in frontal and occipital regions. Additionally, patients displayed weaker sub-network connectivity in distributed regions. Rich-club analysis revealed subtly reduced density in patients, which did not withstand multiple comparison correction. However, hub identification in most participants indicated differentially affected rich-club membership in the BD group, with two hubs absent when compared with controls, namely the superior frontal gyrus and thalamus.
Conclusions
This graph theory analysis presents a thorough investigation of topological features of connectivity in euthymic BD. Abnormalities of global and local measures and network components provide further neuroanatomically specific evidence for distributed dysconnectivity as a trait feature of BD.
Giant ragweed has been increasing as a major weed of row crops in the last
30 yr, but quantitative data regarding its pattern and mechanisms of spread
in crop fields are lacking. To address this gap, we conducted a Web-based
survey of certified crop advisors in the U.S. Corn Belt and Ontario, Canada.
Participants were asked questions regarding giant ragweed and crop
production practices for the county of their choice. Responses were mapped
and correlation analyses were conducted among the responses to determine
factors associated with giant ragweed populations. Respondents rated giant
ragweed as the most or one of the most difficult weeds to manage in 45% of
421 U.S. counties responding, and 57% of responding counties reported giant
ragweed populations with herbicide resistance to acetolactate synthase
inhibitors, glyphosate, or both herbicides. Results suggest that giant
ragweed is increasing in crop fields outward from the east-central U.S. Corn
Belt in most directions. Crop production practices associated with giant
ragweed populations included minimum tillage, continuous soybean, and
multiple-application herbicide programs; ecological factors included giant
ragweed presence in noncrop edge habitats, early and prolonged emergence,
and presence of the seed-burying common earthworm in crop fields. Managing
giant ragweed in noncrop areas could reduce giant ragweed migration from
noncrop habitats into crop fields and slow its spread. Where giant ragweed
is already established in crop fields, including a more diverse combination
of crop species, tillage practices, and herbicide sites of action will be
critical to reduce populations, disrupt emergence patterns, and select
against herbicide-resistant giant ragweed genotypes. Incorporation of a
cereal grain into the crop rotation may help suppress early giant ragweed
emergence and provide chemical or mechanical control options for
late-emerging giant ragweed.