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Analysis of food webs is important for defining functional components of ecosystems, but dietary data are often difficult to obtain and coarsely characterised. We compared three methods of rainbow trout (Oncorhynchus mykiss (Walbaum); Salmoniformes: Salmonidae) and prickly sculpin (Cottus asper Richardson; Scorpaeniformes: Cottidae) gut content analysis: traditional morphological taxonomy of prey items, genetic sequencing of individual prey items, and next-generation sequencing of homogenised gut contents. Prey analysis of invertebrates by morphological identification allowed order-level classifications and produced ecologically important count and mass data. Sequencing individual specimens provided greater taxonomic resolution, while next-generation sequencing of stomach contents revealed more prey diversity in the diets of both fish species as it was possible to detect prey that were degraded beyond visual recognition. Both fish species exhibited generalist feeding characteristics; however, terrestrial Insecta were a large diet component for rainbow trout. This study demonstrates an efficient approach for prey analysis using molecular techniques that complement traditional taxonomy.
Personal protective equipment (PPE) is worn by prehospital providers (PHPs) for protection from hazardous exposures. Evidence regarding the ability of PHPs to perform resuscitation procedures has been described in adult but not pediatric models. This study examined the effects of PPE on the ability of PHPs to perform resuscitation procedures on pediatric patients.
This prospective study was conducted at a U.S. simulation center. Paramedics wore normal attire at the baseline session and donned full Level B PPE for the second session. During each session, they performed timed sets of psychomotor tasks simulating clinical care of a critically ill pediatric patient. The difference in time to completion between baseline and PPE sessions per task was examined using Wilcoxon signed-rank tests.
A total of 50 paramedics completed both sessions. Median times for task completion at the PPE sessions increased significantly from baseline for several procedures: tracheal intubation (+4.5 seconds, P=0.01), automated external defibrillator (AED) placement (+9.5 seconds, P=0.01), intraosseous line insertion (+7 seconds, P<.0001), tourniquet (+8.5 seconds, P<.0001), intramuscular injection (+21–23 seconds, P<.0001), and pulse oximetry (+4 seconds, P<.0001). There was no significant increase in completion time for bag-mask ventilation or autoinjector use.
PPE did not have a significant impact on PHPs performing critical tasks while caring for a pediatric patient with a highly infectious or chemical exposure. This information may guide PHPs faced with the situation of resuscitating children while wearing Level B PPE.
Cognitive impairment associated with lifetime major depressive disorder (MDD) is well-supported by meta-analytic studies, but population-based estimates remain scarce. Previous UK Biobank studies have only shown limited evidence of cognitive differences related to probable MDD. Using updated cognitive and clinical assessments in UK Biobank, this study investigated population-level differences in cognitive functioning associated with lifetime MDD.
Associations between lifetime MDD and cognition (performance on six tasks and general cognitive functioning [g-factor]) were investigated in UK Biobank (N-range 7,457–14,836, age 45–81 years, 52% female), adjusting for demographics, education, and lifestyle. Lifetime MDD classifications were based on the Composite International Diagnostic Interview. Within the lifetime MDD group, we additionally investigated relationships between cognition and (a) recurrence, (b) current symptoms, (c) severity of psychosocial impairment (while symptomatic), and (d) concurrent psychotropic medication use.
Lifetime MDD was robustly associated with a lower g-factor (β = −0.10, PFDR = 4.7 × 10−5), with impairments in attention, processing speed, and executive functioning (β ≥ 0.06). Clinical characteristics revealed differential profiles of cognitive impairment among case individuals; those who reported severe psychosocial impairment and use of psychotropic medication performed worse on cognitive tests. Severe psychosocial impairment and reasoning showed the strongest association (β = −0.18, PFDR = 7.5 × 10−5).
Findings describe small but robust associations between lifetime MDD and lower cognitive performance within a population-based sample. Overall effects were of modest effect size, suggesting limited clinical relevance. However, deficits within specific cognitive domains were more pronounced in relation to clinical characteristics, particularly severe psychosocial impairment.
UK Biobank is a well-characterised cohort of over 500 000 participants including genetics, environmental data and imaging. An online mental health questionnaire was designed for UK Biobank participants to expand its potential.
Describe the development, implementation and results of this questionnaire.
An expert working group designed the questionnaire, using established measures where possible, and consulting a patient group. Operational criteria were agreed for defining likely disorder and risk states, including lifetime depression, mania/hypomania, generalised anxiety disorder, unusual experiences and self-harm, and current post-traumatic stress and hazardous/harmful alcohol use.
A total of 157 366 completed online questionnaires were available by August 2017. Participants were aged 45–82 (53% were ≥65 years) and 57% women. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status. Lifetime depression was a common finding, with 24% (37 434) of participants meeting criteria and current hazardous/harmful alcohol use criteria were met by 21% (32 602), whereas other criteria were met by less than 8% of the participants. There was extensive comorbidity among the syndromes. Mental disorders were associated with a high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation.
The UK Biobank questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed because of selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health.
Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.
In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).
AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.
Refractory ventricular fibrillation encountered during cardiac arrest has a mortality rate of 97%.1 As per the advanced cardiac life support (ACLS) guidelines, the management algorithm of ventricular fibrillation consists of chest compressions, epinephrine, defibrillation, and anti-arrhythmics.2 There have been reports describing the use of the fast-acting selective β-blocker, esmolol, and dual-sequential defibrillation in the management of ventricular fibrillation that is refractory to standard ACLS. We present a case of a 24-year-old male who had an out-of-hospital cardiac arrest, with refractory ventricular fibrillation despite high-quality cardiopulmonary resuscitation (CPR) and ACLS management. Along with standard ACLS, triple-sequential defibrillation was used to achieve return of spontaneous circulation (ROSC) after 82 minutes of downtime. An electrocardiogram (ECG) after ROSC showed an ST-elevation myocardial infarction (MI), and the patient underwent angiography showing a 100% occlusion of his left anterior descending artery. Following management of his coronary artery disease, he was discharged from the hospital 16 days later and was neurologically intact.
Major depressive disorder and neuroticism (Neu) share a large genetic basis. We sought to determine whether this shared basis could be decomposed to identify genetic factors that are specific to depression.
We analysed summary statistics from genome-wide association studies (GWAS) of depression (from the Psychiatric Genomics Consortium, 23andMe and UK Biobank) and compared them with GWAS of Neu (from UK Biobank). First, we used a pairwise GWAS analysis to classify variants as associated with only depression, with only Neu or with both. Second, we estimated partial genetic correlations to test whether the depression's genetic link with other phenotypes was explained by shared overlap with Neu.
We found evidence that most genomic regions (25/37) associated with depression are likely to be shared with Neu. The overlapping common genetic variance of depression and Neu was genetically correlated primarily with psychiatric disorders. We found that the genetic contributions to depression, that were not shared with Neu, were positively correlated with metabolic phenotypes and cardiovascular disease, and negatively correlated with the personality trait conscientiousness. After removing shared genetic overlap with Neu, depression still had a specific association with schizophrenia, bipolar disorder, coronary artery disease and age of first birth. Independent of depression, Neu had specific genetic correlates in ulcerative colitis, pubertal growth, anorexia and education.
Our findings demonstrate that, while genetic risk factors for depression are largely shared with Neu, there are also non-Neu-related features of depression that may be useful for further patient or phenotypic stratification.
The SCN5A gene is implicated in many arrhythmogenic and cardiomyopathic processes. We identified a novel SCN5A variant in a family with significant segregation in individuals affected with progressive sinus and atrioventricular nodal disease, atrial arrhythmia, dilated cardiomyopathy, and early sudden cardiac arrest.
A patient pedigree was created following the clinical evaluation of three affected individuals, two monozygotic twins and a paternal half-brother, which lead to the evaluation of a paternal half-sister (four siblings with the same father and three mothers) all of whom experienced varying degrees of atrial arrhythmias, conduction disease, and dilated cardiomyopathy in addition to a paternal history of unexplained death in his 50s with similar autopsy findings. The index male underwent sequencing of 58 genes associated with cardiomyopathies. Sanger sequencing was used to provide data for bases with insufficient coverage and for bases in some known regions of genomic segmental duplications. All clinically significant and novel variants were confirmed by independent Sanger sequencing.
All relatives tested were shown to have the same SCN5A variant of unknown significance (p. Asp197His) and the monozygotic twins shared a co-occurring NEXN (p. Glu575*). Segregation analysis demonstrates likely pathogenic trait for the SCN5A variant with an additional possible role for the NEXN variant in combination.
There is compelling clinical evidence suggesting that the SCN5A variant p. Asp197His may be re-classified as likely pathogenic based on the segregation analysis of our family of interest. Molecular mechanism studies are pending.
The rocky shores of the north-east Atlantic have been long studied. Our focus is from Gibraltar to Norway plus the Azores and Iceland. Phylogeographic processes shape biogeographic patterns of biodiversity. Long-term and broadscale studies have shown the responses of biota to past climate fluctuations and more recent anthropogenic climate change. Inter- and intra-specific species interactions along sharp local environmental gradients shape distributions and community structure and hence ecosystem functioning. Shifts in domination by fucoids in shelter to barnacles/mussels in exposure are mediated by grazing by patellid limpets. Further south fucoids become increasingly rare, with species disappearing or restricted to estuarine refuges, caused by greater desiccation and grazing pressure. Mesoscale processes influence bottom-up nutrient forcing and larval supply, hence affecting species abundance and distribution, and can be proximate factors setting range edges (e.g., the English Channel, the Iberian Peninsula). Impacts of invasive non-native species are reviewed. Knowledge gaps such as the work on rockpools and host–parasite dynamics are also outlined.
Substantial clinical heterogeneity of major depressive disorder (MDD) suggests it may group together individuals with diverse aetiologies. Identifying distinct subtypes should lead to more effective diagnosis and treatment, while providing more useful targets for further research. Genetic and clinical overlap between MDD and schizophrenia (SCZ) suggests an MDD subtype may share underlying mechanisms with SCZ.
The present study investigated whether a neurobiologically distinct subtype of MDD could be identified by SCZ polygenic risk score (PRS). We explored interactive effects between SCZ PRS and MDD case/control status on a range of cortical, subcortical and white matter metrics among 2370 male and 2574 female UK Biobank participants.
There was a significant SCZ PRS by MDD interaction for rostral anterior cingulate cortex (RACC) thickness (β = 0.191, q = 0.043). This was driven by a positive association between SCZ PRS and RACC thickness among MDD cases (β = 0.098, p = 0.026), compared to a negative association among controls (β = −0.087, p = 0.002). MDD cases with low SCZ PRS showed thinner RACC, although the opposite difference for high-SCZ-PRS cases was not significant. There were nominal interactions for other brain metrics, but none remained significant after correcting for multiple comparisons.
Our significant results indicate that MDD case-control differences in RACC thickness vary as a function of SCZ PRS. Although this was not the case for most other brain measures assessed, our specific findings still provide some further evidence that MDD in the presence of high genetic risk for SCZ is subtly neurobiologically distinct from MDD in general.
The initial classic Fontan utilising a direct right atrial appendage to pulmonary artery anastomosis led to numerous complications. Adults with such complications may benefit from conversion to a total cavo-pulmonary connection, the current standard palliation for children with univentricular hearts.
A single institution, retrospective chart review was conducted for all Fontan conversion procedures performed from July, 1999 through January, 2017. Variables analysed included age, sex, reason for Fontan conversion, age at Fontan conversion, and early mortality or heart transplant within 1 year after Fontan conversion.
A total of 41 Fontan conversion patients were identified. Average age at Fontan conversion was 24.5 ± 9.2 years. Dominant left ventricular physiology was present in 37/41 (90.2%) patients. Right-sided heart failure occurred in 39/41 (95.1%) patients and right atrial dilation was present in 33/41 (80.5%) patients. The most common causes for Fontan conversion included atrial arrhythmia in 37/41 (90.2%), NYHA class II HF or greater in 31/41 (75.6%), ventricular dysfunction in 23/41 (56.1%), and cirrhosis or fibrosis in 7/41 (17.1%) patients. Median post-surgical follow-up was 6.2 ± 4.9 years. Survival rates at 30 days, 1 year, and greater than 1-year post-Fontan conversion were 95.1, 92.7, and 87.8%, respectively. Two patients underwent heart transplant: the first within 1 year of Fontan conversion for heart failure and the second at 5.3 years for liver failure.
Fontan conversion should be considered early when atrial arrhythmias become common rather than waiting for severe heart failure to ensue, and Fontan conversion can be accomplished with an acceptable risk profile.
Elevated left ventricular end diastolic pressure is a risk factor for ventricular arrhythmias in patients with tetralogy of Fallot. The objective of this retrospective study was to identify echocardiographic measures associated with left ventricular end diastolic pressure >12 mmHg in this population. Repaired tetralogy of Fallot patients age ≥13 years, who underwent a left heart catheterisation within 7 days of having an echocardiogram were evaluated. Univariate comparison was made in echocardiographic and clinical variables between patients with left ventricular end diastolic pressure >12 versus ≤12 mmHg. Ninety-four patients (54% male) with a median age of 24.6 years were included. Thirty-four (36%) had left ventricular end diastolic pressure >12 mmHg. Patients with left ventricular end diastolic pressure >12mmHg were older (median 32.9 versus 24.0 years, p = 0.02), more likely to have a history of an aortopulmonary shunt (62% versus 38%, p = 0.03), and have a diagnosis of hypertension (24% versus 7%, p = 0.03) compared to those with left ventricular end diastolic pressure ≤12 mmHg. There were no significant differences in mitral valve E/A ratio, annular e’ velocity, or E/e’ ratio between patients with left ventricular end diastolic pressure >12 versus ≤12 mmHg. Patients with left ventricular end diastolic pressure >12mmHg had larger left atrial area (mean 17.7 versus 14.0 cm2, p = 0.03) and larger left atrium anterior–posterior diameter (mean 36.0 versus 30.6 mm, p = 0.004). In conclusion, typical echocardiographic measures of left ventricular diastolic dysfunction may not be reliable in tetralogy of Fallot patients. Prospective studies with the use of novel echocardiographic measures are needed.
The Bulge Asymmetries and Dynamical Evolution (BAaDE) survey aims to use circumstellar SiO maser line-of-sight velocities as probes for the Galactic gravitational potential and dynamical structure. The SiO masers are detected at a high rate in specific color-selected MSX infrared sources. Furthermore, the SiO maser properties and line ratios, in combination with infrared spectral energy distributions and location in the Galaxy, will statistically yield detailed information on population and evolution of low- to intermediate-mass evolved stars in the Galaxy.
Stuart foreign affairs in the seventeenth century were complex, often seemingly contradictory and rarely straightforward. On the eve of the Thirty Years’ War Europe was composed of a diverse range of powers, and the largest of these – namely France, Spain and the Holy Roman Empire – have attracted the bulk of scholarship. Unfortunately by doing so a variety of other city states, duchies, republics and kingdoms have been overlooked. There has often been a historiographic assumption that early modern Europe functioned in the same way as the ‘great power’ politics of the nineteenth century, which was simply not the case. Indeed it is worth noting that although in modern Europe Denmark is a small polity, in early modern Europe the control of the Danish sound allowed the king of Denmark-Norway to exert significant influence over both Scandinavian and German affairs. The Holy Roman Empire itself was not an absolutist centralized state ruled by the emperor, but a myriad of German states bound within the highly complex imperial constitution. In recognizing the differences between seventeenth- and nineteenth-century Europe, and by examining the role of these other early modern European powers, a more accurate, if more complex, picture emerges.
This chapter stems from two relatively recent historiographical lines of enquiry, both of which owe a debt to this shift. The first is the development of a wider view of Europe reaching beyond the Mediterranean world and western Europe. This broader approach spans from the Baltic to the Mediterranean and from Muscovy to the coast of Ireland, and through the assessment of the role of many of the perceived lesser powers a host of challenges to some long-held historiographical concepts have been developed. Spain and France can be seen as two powers within a wider framework of alliances. A number of the Stuarts’ closest allies have fallen victim to this oversight. This includes the Palatinate marriage that has often been simply ignored as an unimportant choice in contrast to the Stuarts’ pursuit of a match with France or Spain. The interaction between Scotland and Scandinavia has arguably received even less attention.
Many scholars agree that the Internet plays a pivotal role in self-radicalization, which can lead to behaviors ranging from lone-wolf terrorism to participation in white nationalist rallies to mundane bigotry and voting for extremist candidates. However, the mechanisms by which the Internet facilitates self-radicalization are disputed; some fault the individuals who end up self-radicalized, while others lay the blame on the technology itself. In this paper, we explore the role played by technological design decisions in online self-radicalization in its myriad guises, encompassing extreme as well as more mundane forms. We begin by characterizing the phenomenon of technological seduction. Next, we distinguish between top-down seduction and bottom-up seduction. We then situate both forms of technological seduction within the theoretical model of dynamical systems theory. We conclude by articulating strategies for combating online self-radicalization.
We report on the Bulge Asymmetries and Dynamic Evolution (BAaDE) survey which has observed 19 000 MSX color selected red giant stars for SiO maser emission at 43 GHz with the VLA and is in the process of observing 9 000 of these stars with ALMA at 86 GHz in the Southern sky. Our setup covers the main maser transitions, as well as those of isotopologues and selected lines of carbon-bearing species. Observations of this set of lines allow a far-reaching catalog of line-of-sight velocities in the dust-obscured regions where optical surveys cannot reach. Our preliminary detection rate is close to 70%, predicting a wealth of new information on the distribution of metal rich stars, their kinematics as function of location in the Galaxy, as well as the occurrence of lines and line ratios between the different transitions in combination with the spectral energy distribution from about 1 to 100 μm. Similar to the OH/IR stars, a clear kinematic signature between disk and bulge stars can be seen. Furthermore, the SiO J = →10 (v=3) line plays a prominent role in the derived maser properties.