To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
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.
To compare the risk of mild cognitive impairment (MCI) among a wide range of ethnoracial groups in the US.
Non-probabilistic longitudinal clinical research.
Participants enrolling into the National Alzheimer’s Coordinating Center Unified Data Set recruited via multiple approaches including clinician referral, self-referral by patients or family members, or active recruitment through community organizations.
Cognitively normal individuals 55 and older at the initial visit, who reported race and ethnicity information, with at least two visits between September 2005 and November 2018.
Ethnoracial information was self-reported and grouped into non-Latino Whites, Asian Americans, Native Americans, African Americans (AAs), and individuals simultaneously identifying as AAs and another minority race (AA+), as well as Latinos of Caribbean, Mexican, and Central/South American origin. MCI was evaluated clinically following standard criteria. Four competing risk analysis models were used to calculate MCI risk adjusting for risk of death, including an unadjusted model, and models adjusting for non-modifiable and modifiable risk factors.
After controlling for sex and age at initial visit, subhazard ratios of MCI were statistically higher than non-Latino Whites among Native Americans (1.73), Caribbean Latinos (1.80), and Central/South American Latinos (1.55). Subhazard ratios were higher among AA+ compared to non-Latino Whites only in the model controlling for all risk factors (1.40).
Compared to non-Latino Whites, MCI risk was higher among Caribbean and South/Central American Latinos as well as Native Americans and AA+. The factors explaining the differential MCI risk among ethnoracial groups are not clear and warrant future research.
Negative affect (NA) has been suggested to be both an antecedent and a consequence of auditory verbal hallucinations (AVH). Furthermore, negative appraisals of voices have been theorized to contribute to the maintenance of AVH. Using the experience sampling method (ESM), this study examined the bi-directional relationship between NA and AVH, and the moderating effect of negative beliefs about voices.
Forty-seven patients diagnosed with schizophrenia spectrum disorders with frequent AVH completed a clinical interview, followed by ESM for 10 times a day over 6 days on an electronic device. Time-lagged analyses were conducted using multilevel regression modeling. Beliefs about voices were assessed at baseline.
A total of 1654 data points were obtained. NA predicted an increase in AVH in the subsequent moment, and AVH predicted an increase in NA in the subsequent moment. Baseline beliefs about voices as malevolent and omnipotent significantly strengthened the association between NA and AVH within the same moment. In addition, the belief of omnipotence was associated with more hallucinatory experiences in the moment following NA. However, beliefs about voices were not associated directly with momentary levels of NA or AVH.
Experiences of NA and AVH drove each other, forming a feedback loop that maintained the voices. The associations between NA and AVH, either within the same moment or across moments, were exacerbated by negative beliefs about voices. Our results suggest that affect-improving interventions may stop the feedback loop and reduce AVH frequency.
Abnormal effort-based decision-making represents a potential mechanism underlying motivational deficits (amotivation) in psychotic disorders. Previous research identified effort allocation impairment in chronic schizophrenia and focused mostly on physical effort modality. No study has investigated cognitive effort allocation in first-episode psychosis (FEP).
Cognitive effort allocation was examined in 40 FEP patients and 44 demographically-matched healthy controls, using Cognitive Effort-Discounting (COGED) paradigm which quantified participants’ willingness to expend cognitive effort in terms of explicit, continuous discounting of monetary rewards based on parametrically-varied cognitive demands (levels N of N-back task). Relationship between reward-discounting and amotivation was investigated. Group differences in reward-magnitude and effort-cost sensitivity, and differential associations of these sensitivity indices with amotivation were explored.
Patients displayed significantly greater reward-discounting than controls. In particular, such discounting was most pronounced in patients with high levels of amotivation even when N-back performance and reward base amount were taken into consideration. Moreover, patients exhibited reduced reward-benefit sensitivity and effort-cost sensitivity relative to controls, and that decreased sensitivity to reward-benefit but not effort-cost was correlated with diminished motivation. Reward-discounting and sensitivity indices were generally unrelated to other symptom dimensions, antipsychotic dose and cognitive deficits.
This study provides the first evidence of cognitive effort-based decision-making impairment in FEP, and indicates that decreased effort expenditure is associated with amotivation. Our findings further suggest that abnormal effort allocation and amotivation might primarily be related to blunted reward valuation. Prospective research is required to clarify the utility of effort-based measures in predicting amotivation and functional outcome in FEP.
Seasonal influenza virus epidemics have a major impact on healthcare systems. Data on population susceptibility to emerging influenza virus strains during the interepidemic period can guide planning for resource allocation of an upcoming influenza season. This study sought to assess the population susceptibility to representative emerging influenza virus strains collected during the interepidemic period. The microneutralisation antibody titers (MN titers) of a human serum panel against representative emerging influenza strains collected during the interepidemic period before the 2018/2019 winter influenza season (H1N1-inter and H3N2-inter) were compared with those against influenza strains representative of previous epidemics (H1N1-pre and H3N2-pre). A multifaceted approach, incorporating both genetic and antigenic data, was used in selecting these representative influenza virus strains for the MN assay. A significantly higher proportion of individuals had a ⩾four-fold reduction in MN titers between H1N1-inter and H1N1-pre than that between H3N2-inter and H3N2-pre (28.5% (127/445) vs. 4.9% (22/445), P < 0.001). The geometric mean titer (GMT) of H1N1-inter was significantly lower than that of H1N1-pre (381 (95% CI 339–428) vs. 713 (95% CI 641–792), P < 0.001), while there was no significant difference in the GMT between H3N2-inter and H3N2-pre. Since A(H1N1) predominated the 2018–2019 winter influenza epidemic, our results corroborated the epidemic subtype.
Better understanding of interplay among symptoms, cognition and functioning in first-episode psychosis (FEP) is crucial to promoting functional recovery. Network analysis is a promising data-driven approach to elucidating complex interactions among psychopathological variables in psychosis, but has not been applied in FEP.
This study employed network analysis to examine inter-relationships among a wide array of variables encompassing psychopathology, premorbid and onset characteristics, cognition, subjective quality-of-life and psychosocial functioning in 323 adult FEP patients in Hong Kong. Graphical Least Absolute Shrinkage and Selection Operator (LASSO) combined with extended Bayesian information criterion (BIC) model selection was used for network construction. Importance of individual nodes in a generated network was quantified by centrality analyses.
Our results showed that amotivation played the most central role and had the strongest associations with other variables in the network, as indexed by node strength. Amotivation and diminished expression displayed differential relationships with other nodes, supporting the validity of two-factor negative symptom structure. Psychosocial functioning was most strongly connected with amotivation and was weakly linked to several other variables. Within cognitive domain, digit span demonstrated the highest centrality and was connected with most of the other cognitive variables. Exploratory analysis revealed no significant gender differences in network structure and global strength.
Our results suggest the pivotal role of amotivation in psychopathology network of FEP and indicate its critical association with psychosocial functioning. Further research is required to verify the clinical significance of diminished motivation on functional outcome in the early course of psychotic illness.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Agents that block the renin–angiotensin system (RAS) improve glucoregulation in the metabolic syndrome disorder. We evaluated the effects of egg white hydrolysate (EWH), previously shown to modulate the protein abundance of RAS component in vivo, on glucose homeostasis in diet-induced insulin-resistant rats. Sprague–Dawley rats were fed a high-fat diet (HFD) for 6 weeks to induce insulin resistance. They were then randomly divided into four groups receiving HFD or HFD supplemented with different concentrations of EWH (1, 2 and 4 %) for another 6 weeks in the first trial. In the second trial, insulin-resistant rats were divided into two groups receiving only HFD or HFD+4 % EWH for 6 weeks. Glucose homeostasis was assessed by oral glucose tolerance and insulin tolerance tests. Insulin signalling and protein abundance of RAS components, gluconeogenesis enzymes and PPARγ were evaluated in muscle, fat and liver. Adipocyte morphology and inflammatory markers were evaluated. In vivo administration of EWH increased insulin sensitivity, improved oral glucose tolerance (P < 0·0001) and reduced systemic inflammation (P < 0·05). EWH potentiated insulin-induced Akt phosphorylation in muscle (P = 0·0341) and adipose tissue (P = 0·0276), but minimal differences in the protein abundance of tissue RAS components between the EWH and control groups were observed. EWH treatment also reduced adipocyte size (P = 0·0383) and increased PPARγ2 protein abundance (P = 0·0237). EWH treatment yielded positive effects on the inflammatory profile, glucose tolerance, insulin sensitivity and adipocyte differentiation in HFD-induced insulin resistance rats. The involvement of local RAS activity requires further investigation.
Innovation Concept: Mass Casualty Incidents (MCI) are complex events that most paramedics encounter only a few times in their careers. Triaging and managing multiple patients during an incident requires different skills than typically practiced by prehospital providers. Simulation and drills can provide an opportunity to practice those skills, but are costly and resource intensive while only allowing a few providers to be in a triage or leadership role. It is important to find engaging and less expensive methods for teaching MCI triage and initial scene management. Methods: The authors have developed and are testing a card game based on the previously published GridlockED board game. The game was developed utilizing an iterative process previously described. This game was tested with paramedics as well as other emergency medicine learners to determine usability, engagement, fidelity, as well as usefulness in teaching MCI triage and patient-flow concepts. Curriculum, Tool or Material: The card game provides a focused learning experience to allow providers to practice initial triage of multiple injured patients as well as manage patient flow from the scene to area hospitals when faced with limited prehospital resources and capabilities. Players work together in various simulated scenarios to correctly triage injured patients and send them to the correct healthcare facility. Conclusion: Serious gaming has gained momentum in medical education. Developing novel curriculae around low frequency, high stakes situations using a game like TriagED may hold the key to ensure prehospital care providers are trained for these incidents. In the future, games which integrate an element of Incident Command or receiving hosptials (e.g. full integration with GridlockED game) may help to further explore the relationship between scene management and patient flow within receiving hospitals.
Introduction: Many drugs, including cannabis and alcohol, cause impairment and contribute to motor vehicle collisions (MVCs). Policy makers require knowledge of the prevalence of drug use in crash-involved drivers, and types of drugs used in order to develop effective prevention programs. This issue is particularly relevant with the recent legalization of cannabis. We aim to study the prevalence of alcohol, cannabis, sedating medications, and other drugs in injured drivers from 4 Canadian Provinces. Methods: This prospective cohort study obtained excess clinical blood samples from consecutive injured drivers who attended a participating Canadian trauma centre following a MVC. Blood samples were analyzed using a broad spectrum toxicology screen capable of detecting cannabinoids, cocaine, amphetamines (including their major analogues), and opioids as well as psychotropic pharmaceuticals (including antihistamines, benzodiazepines, other hypnotics, and sedating antidepressants). Alcohol and cannabinoids were quantified. Health records were reviewed to extract demographic, medical, and MVC information using a standardized data collection tool. Results: This study has been collecting data in 4 trauma centres in British Columbia (BC) since 2011 and was launched in 2 trauma centres in Alberta (AB), 1 in Saskatchewan (SK), and 2 in Ontario (ON) in 2018. In preliminary results from BC (n = 2412), 8% of injured drivers tested positive for THC and 13% for alcohol. Preliminary results from other provinces (n = 301) suggest a regional variation in prevalence of drivers testing positive for THC (10% - 27%), alcohol (17% - 29%), and other drugs. By May 2018, an estimated 4500 cases from BC, 600 from AB, 150 from SK, and 650 from ON will have been analyzed. We will report the prevalence of positive tests for alcohol, THC, other recreational drugs, and sedating medications, pre and post cannabis legalization. The number of cases with alcohol and/or THC levels above Canadian per se limits will also be reported. Results will be reported according to province, driver sex, age, single vs. multi vehicle crashes, and requirement for hospital admission. Conclusion: This will be among the largest international datasets on drug use by injured drivers. Our findings will provide patterns of drug and alcohol impairment in 4 Canadian provinces pre and post cannabis legalization. The significance of these findings and implication for impaired driving policy and prevention programs in Canada will be discussed.
Upper respiratory tract infections (URTIs) account for substantial attendances at emergency departments (EDs). There is a need to elucidate determinants of antibiotic prescribing in time-strapped EDs – popular choices for primary care despite highly accessible primary care clinics. Semi-structured in-depth interviews were conducted with purposively sampled physicians (n = 9) in an adult ED in Singapore. All interviews were analysed using thematic analysis and further interpreted using the Social Ecological Model to explain prescribing determinants. Themes included: (1) reliance on clinical knowledge and judgement, (2) patient-related factors, (3) patient–physician relationship factors, (4) perceived practice norms, (5) policies and treatment guidelines and (6) patient education and awareness. The physicians relied strongly on their clinical knowledge and judgement in managing URTI cases and seldom interfered with their peers’ clinical decisions. Despite departmental norms of not prescribing antibiotics for URTIs, physicians would prescribe antibiotics when faced with uncertainty in patients’ diagnoses, treating immunocompromised or older patients with comorbidities, and for patients demanding antibiotics, especially under time constraints. Participants had a preference for antibiotic prescribing guidelines based on local epidemiology, but viewed hospital policies on prescribing as a hindrance to clinical judgement. Participants highlighted the need for more public education and awareness on the appropriate use of antibiotics and management of URTIs. Organisational practice norms strongly influenced antibiotic prescribing decisions by physicians, who can be swayed by time pressures and patient demands. Clinical decision support tools, hospital guidelines and patient education targeting at individual, interpersonal and community levels could reduce unnecessary antibiotic use.
In 2005, using a famous lemma of Atkin and Swinnerton-Dyer (Some properties of partitions, Proc. Lond. Math. Soc. (3) 4 (1954), 84–106), Yesilyurt (Four identities related to third order mock theta functions in Ramanujan’s lost notebook, Adv. Math. 190 (2005), 278–299) proved four identities for third order mock theta functions found on pages 2 and 17 in Ramanujan’s lost notebook. The primary purpose of this paper is to offer new proofs in the spirit of what Ramanujan might have given in the hope that a better understanding of the identities might be gained. Third order mock theta functions are intimately connected with ranks of partitions. We prove new dissections for two rank generating functions, which are keys to our proof of the fourth, and the most difficult, of Ramanujan’s identities. In the last section of this paper, we establish new relations for ranks arising from our dissections of rank generating functions.