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.
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.
We investigated how initial conflicts in adolescent romantic relationships escalate into serious forms of conflict, including intimate partner violence (IPV). We focused on whether adolescents’ micro-level interaction patterns, i.e., coercion and positive engagement, mediated between conflict and future IPV. The sample consisted of 91 heterosexual couples, aged 13 to 18 years (M = 16.5, SD = 0.99) from a diverse background (42% Hispanic/Latino, 42% White). Participants completed surveys about conflict at Time 1, and they participated in videotaped conflict and jealousy discussions. At Time 2, participants completed surveys about conflict and IPV, and an average daily conflict score was calculated from ecological momentary assessments. Multilevel hazard models revealed that we did not find support for dyadic coercion as a risk process leading to escalations in conflict. However, a higher likelihood of ending dyadic positive behaviors mediated between earlier levels of conflict and a latent construct of female conflict and IPV. Classic coercive dynamics may not apply to adolescent romantic relationships. Instead, not being able to reinforce levels of positivity during conflict predicted conflict and IPV as reported by females. The implications of these findings for understanding coercion in the escalation from conflict to IPV in adolescent romantic relationships are discussed.
Adolescence is a period of heightened susceptibility to peer influences, and deviant peer affiliation has well-established implications for the development of psychopathology. However, little is known about the role of brain functions in pathways connecting peer contexts and health risk behaviors. We tested developmental cascade models to evaluate contributions of adolescent risk taking, peer influences, and neurobehavioral variables of risk processing and cognitive control to substance use among 167 adolescents who were assessed annually for four years. Risk taking at Time 1 was related to substance use at Time 4 indirectly through peer substance use at Time 2 and insular activation during risk processing at Time 3. Furthermore, neural cognitive control moderated these effects. Greater insular activation during risk processing was related to higher substance use for those with greater medial prefrontal cortex activation during cognitive control, but it was related to lower substance use among those with lower medial prefrontal cortex activation during cognitive control. Neural processes related to risk processing and cognitive control play a crucial role in the processes linking risk taking, peer substance use, and adolescents’ own substance use.
This is a copy of the slides presented at the meeting but not formally written up for the volume.
Stripe domains in ferroelectric thin films form in order to minimize the total energy of the film. It has been known for some time that a stable configuration is reached when the decrease in elastic energy from domain formation is balanced by the energetic costs of domain wall formation, local elastic strains in the substrate, and internal electric field formation from domain polarizations. The size and strain of each domain is determined by the lattice mismatch and the energetic costs of interface formation. Recent piezoelectric force microscopy measurements have shown that BiFeO3 (BFO) films on SrRuO3/SrTiO3 (001) substrates form striped polarization domains. Since the details of the local structure and polarization cannot be measured at the same time with conventional techniques, we have used synchrotron x-ray microdiffraction to study these effects. Probing only a few domains at a time with the submicron x-ray spot resulted in a diffraction pattern near the substrate (103) reflection consisting of several BFO peaks. We have unambiguously assigned these peaks to individual structural variants. Based on these results, we propose a physical model that includes the striped domains. The structural variants within the stripes are similar to those predicted by striped patterns in rhombohedral films which minimize elastic energy. The local piezoelectric properties were measured using time-resolved microdiffraction in order to examine the role of the striped domains in the linear responses of the film. The out of plane piezoelectric coefficient d33 was approximately 50 pm/V and the piezoelectric strain was proportional to electric field was up to 0.55%, the maximum strain we have measured. The projection of the in-plane piezoelectric coefficients onto the reciprocal space maps for different structural variants had vastly different values due to the differences in orientation of the domains.
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.
The growing availability of mobile technologies has contributed to an increase in mobile-assisted language learning in which learners can autonomously study a second language (L2) anytime or anywhere (e.g. Kukulska-Hulme, Lee & Norris, 2017; Reinders & Benson, 2017). Research investigating the effectiveness of such study for L2 learning, however, has been limited, especially regarding large-scale commercial L2 learning apps, such as Duolingo. Although one commissioned research study found favorable language learning outcomes (Vesselinov & Grego, 2012), limited independent research has reported issues related to learner persistence, motivation, and program efficacy (Lord, 2015; Nielson, 2011). The current study investigates the semester-long learning experiences and results of nine participants learning Turkish on Duolingo. The participants showed improvement on L2 measures at the end of the study, and results indicate a positive, moderate correlation between the amount of time spent on Duolingo and learning gains. In terms of perceptions of their experiences, the participants generally viewed Duolingo’s flexibility and gamification aspects positively; however, variability in motivation to study and frustration with instructional materials were also expressed.
This study of loneliness across adult lifespan examined its associations with sociodemographics, mental health (positive and negative psychological states and traits), subjective cognitive complaints, and physical functioning.
Analysis of cross-sectional data
340 community-dwelling adults in San Diego, California, mean age 62 (SD = 18) years, range 27–101 years, who participated in three community-based studies.
Loneliness measures included UCLA Loneliness Scale Version 3 (UCLA-3), 4-item Patient-Reported Outcomes Measurement Information System (PROMIS) Social Isolation Scale, and a single-item measure from the Center for Epidemiologic Studies Depression (CESD) scale. Other measures included the San Diego Wisdom Scale (SD-WISE) and Medical Outcomes Survey- Short form 36.
Seventy-six percent of subjects had moderate-high levels of loneliness on UCLA-3, using standardized cut-points. Loneliness was correlated with worse mental health and inversely with positive psychological states/traits. Even moderate severity of loneliness was associated with worse mental and physical functioning. Loneliness severity and age had a complex relationship, with increased loneliness in the late-20s, mid-50s, and late-80s. There were no sex differences in loneliness prevalence, severity, and age relationships. The best-fit multiple regression model accounted for 45% of the variance in UCLA-3 scores, and three factors emerged with small-medium effect sizes: wisdom, living alone and mental well-being.
The alarmingly high prevalence of loneliness and its association with worse health-related measures underscore major challenges for society. The non-linear age-loneliness severity relationship deserves further study. The strong negative association of wisdom with loneliness highlights the potentially critical role of wisdom as a target for psychosocial/behavioral interventions to reduce loneliness. Building a wiser society may help us develop a more connected, less lonely, and happier society.
Point-of-Care Ultrasound (POCUS) has become an important diagnostic tool for hospital-based clinicians. This study assesses the role of POCUS at Pemberton Music Festival 2016 (Pemberton, British Columbia [BC], Canada), a remote mass gathering where physicians face limited resources, complex disposition decisions, and a dynamic clinical environment.
This study prospectively evaluated the impact of POCUS on patient diagnosis, management, and disposition based on the self-report of the study physicians. The authors hypothesized that having ultrasound available for use would aid in diagnostic and management decisions and would reduce the need to transfer patients off-site to other health care facilities, reducing impact on the acute health services in the host community.
A handheld ultrasound was available for use by physicians in the main medical tent. All participating physicians self-reported their training and comfort using POCUS. After each POCUS scan, physicians completed a survey and recorded the indication for use, scans performed, and impact on patient diagnosis, management, and disposition.
In total, POCUS was used on 28 of the 686 patients treated in the main medical tent; POCUS was reported to narrow the differential diagnosis in 64% of cases and altered the working diagnosis in 21% of cases. Its use changed the management plan in 39% of patients. Its use was reported to reduce the burden on broader health care resource utilization in 46% of cases and prevented ambulance transport off-site in 32% of cases (nine cases in total). This corresponded to an absolute risk reduction of 1.3% for the percentage of patients transferred to hospital (PPTH; relative risk reduction of 53%).
Physicians reported that POCUS improved the diagnosis, management, and disposition of select patients at a remote, multi-day music festival. Also, POCUS reduced ambulance transfers off-site and reduced the perceived burden on broader health care utilization.
PragerR, SedgwickC, LundA, KimD, HoB, StachuraM, GutmanS. Prospective Evaluation of Point-of-Care Ultrasound at a Remote, Multi-Day Music Festival. Prehosp Disaster Med. 2018;33(5):484–489.
We evaluated the utility of vancomycin-resistant Enterococcus (VRE) surveillance by varying 2 parameters: admission versus weekly surveillance and perirectal swabbing versus stool sampling.
Prospective, patient-level surveillance program of incident VRE colonization.
Liver transplant surgical intensive care unit (SICU) of a tertiary-care referral medical center with a high prevalence of VRE.
All patients admitted to the SICU from June to August 2015.
We conducted a point-prevalence estimate followed by admission and weekly surveillance by perirectal swabbing and/or stool sampling. Incident colonization was defined as a negative screen followed by positive surveillance. VRE was detected by culture on Remel Spectra VRE chromogenic agar. Microbiologically-confirmed VRE bloodstream infections (BSIs) were tracked for 2 months. Statistical analyses were calculated using the McNemar test, the Fisher exact test, the t test, and the χ2 test.
In total, 91 patients underwent VRE surveillance testing. The point prevalence of VRE colonization was 60.9%; VRE prevalence on admission was 30.1%. Weekly surveillance identified an additional 7 of 28 patients (25.0%) with incident colonization. VRE BSIs were more common in VRE-colonized patients than in noncolonized patients (8 of 43 vs 2 of 48; P=.028). In a direct comparison, perirectal swabs were more sensitive than stool samples in detecting VRE (64 of 67 vs 56 of 67; P=.023). Compliance with perirectal swabbing was 89% (201 of 226) compared to 56% (127 of 226) for stool collection (P≤0.001).
We recommend weekly VRE surveillance over admission-only screening in high-burden units such as liver transplant SICUs. Perirectal swabs had greater collection compliance and sensitivity than stool samples, making them the preferred methodology. Further work may have implications for antimicrobial stewardship and infection control.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
The aim of this study was to investigate the associations for specified substitutions between different subgroups of dairy products and the risk of type 2 diabetes. We used data from the Danish Diet, Cancer and Health cohort including 54 277 men and women aged 50–64 years at baseline. Information regarding intake of dairy products was obtained from a validated FFQ, and cases of type 2 diabetes were identified through the Danish National Diabetes Register. Cox proportional hazards regressions were used to estimate associations. During a median follow-up of 15·3 years, 7137 cases were identified. Low-fat yogurt products in place of whole-fat yogurt products were associated with a higher rate of type 2 diabetes (hazard ratio (HR) 1·17; 95 % CI 1·06, 1·29) per serving/d substituted. Whole-fat yogurt products in place of low-fat milk, whole-fat milk or buttermilk were associated with a lower rate of type 2 diabetes (HR 0·89; 95 % CI 0·83, 0·96; HR 0·89; 95 % CI 0·82, 0·96; HR 0·89; 95 % CI 0·81, 0·97; per serving/d substituted, respectively). The pattern of associations was similar when intake was expressed as kJ/d (kcal/d). These findings suggest that intake of whole-fat yogurt products in place of low-fat yogurt products, low-fat milk, whole-fat milk and buttermilk are associated with a lower rate of type 2 diabetes.
We have previously shown that the minor alleles of vascular endothelial growth factor A (VEGFA) single-nucleotide polymorphism rs833069 and superoxide dismutase 2 (SOD2) single-nucleotide polymorphism rs2758331 are both associated with improved transplant-free survival after surgery for CHD in infants, but the underlying mechanisms are unknown. We hypothesised that one or both of these minor alleles are associated with better systemic ventricular function, resulting in improved survival.
This study is a follow-up analysis of 422 non-syndromic CHD patients who underwent neonatal cardiac surgery with cardiopulmonary bypass. Echocardiographic reports were reviewed. Systemic ventricular function was subjectively categorised as normal, or as mildly, moderately, or severely depressed. The change in function was calculated as the change from the preoperative study to the last available study. Stepwise linear regression, adjusting for covariates, was performed for the outcome of change in ventricular function. Model comparison was performed using Akaike’s information criterion. Only variables that improved the model prediction of change in systemic ventricular function were retained in the final model.
Genetic and echocardiographic data were available for 335/422 subjects (79%). Of them, 33 (9.9%) developed worse systemic ventricular function during a mean follow-up period of 13.5 years. After covariate adjustment, the presence of the VEGFA minor allele was associated with preserved ventricular function (p=0.011).
These data support the hypothesis that the mechanism by which the VEGFA single-nucleotide polymorphism rs833069 minor allele improves survival may be the preservation of ventricular function. Further studies are needed to validate this genotype–phenotype association and to determine whether this mechanism is related to increased vascular endothelial growth factor production.
OBJECTIVES/SPECIFIC AIMS: In this pilot case-control study, the metabolome was quantified in subjects with previously measured serum and clinical biomarkers. The serum metabolome was then integrated with existing serum and clinical biomarkers of WTC-exposed firefighters to identify pathways significant to loss of lung function following acute PM-exposure. This robust subset of metabolite and serum biomarkers may be clinically relevant to predicting progression to lung disease in a larger cohort. METHODS/STUDY POPULATION: Serum drawn within 6 months of 9/11 was analyzed in this pilot. Clinical measures were obtained from electronic medical records. Never-smoking, male, WTC-exposed firefighters with normal pre-9/11 lung function were segregated based on FEV1 percent predicted (FEV1 %Pred) at symptomatic presentation. Cases of WTC-LI (FEV1 %Pred <LLN, n=15) and controls (n=15) were identified from previous cohorts. Ultrahigh performance liquid chromatography tandem mass spectroscopy quantified the metabolomic fingerprints of a group with previously assessed (by multiplex panels; ELISA and Luminex) serum chemokines and cytokines. High-dimensional data analysis and dimension reduction techniques integrated metabolites, cytokines, chemokines, and clinical data to identify pathways of WTC-LI on curated data. Random Forest (RF) out-of-bag estimated success rates were used to measure classification utility of the refined biomarker profile. Principal components analysis (PCA) was used to visualize class separation produced by the refined profile. RESULTS/ANTICIPATED RESULTS: Of the 765 metabolites detected, 580 metabolites were quantified in more than 80% of subjects/group with relative standard deviation ≥15%. Relevant chemokines, cytokines, and clinical biomarkers were included based on previously established clinical importance. Initial PCA explained 34.7% of the variance in the first 3 components. RF was used to identify the top 5% of biomarkers important to class separation. RF of the refined biomarker profile correctly classified cases and controls with a 96.7% estimated success rate. A PCA of the refined metabolic profile now explained 46.2% of the variance in components 1–3, demonstrating improved class separation. Differentiators between cases of WTC-LI and controls included elevated sphingolipids in cases of WTC-LI. The metabolic-inflammatory serum biomarkers MDC, Apo AI, GM-CSF, and heart rate play an important role in class separation. Phospholipids and lysolipids also appeared to differentiate cases of WTC-LI from controls. Specifically, several glycero-phosphatidylcholines (GPC) were elevated in cases of WTC-LI. DISCUSSION/SIGNIFICANCE OF IMPACT: High-dimensional data analysis on the metabolic fingerprints, serum, and clinical biomarker data of a subset of WTC-exposed 9/11 rescue workers has identified pathways associated with the loss of lung function. Sphingolipids, known to function as inflammatory signaling mediators, are thought to play important roles in lung function under both physiological and pathological conditions. Changes in sphingolipid metabolism have been linked to several pulmonary disorders, including asthma, COPD, and acute lung injury. Interestingly, a relation between sphingolipid metabolism and the metabolic-inflammatory pathway is suggested by similarities observed in PCA. Findings of elevated GPCs are similar to COPD literature. Higher levels of GPCs could correspond to elevated levels of lysophosphatidic acid (LPA), a ligand of RAGE. RAGE is a known proinflammatory mediator; LPA species have well-described roles as lipid signaling molecules, function as synthetic intermediates in other metabolic pathways, and were found to be predictive of WTC-LI. Since metabolites are more proximal markers of disease processes, metabolites could capture the complexity of past exposures and, therefore, may better inform treatment. These pathways warrant further investigation into their mechanisms and therapeutic importance.
We describe the design and performance of the Engineering Development Array, which is a low-frequency radio telescope comprising 256 dual-polarisation dipole antennas working as a phased array. The Engineering Development Array was conceived of, developed, and deployed in just 18 months via re-use of Square Kilometre Array precursor technology and expertise, specifically from the Murchison Widefield Array radio telescope. Using drift scans and a model for the sky brightness temperature at low frequencies, we have derived the Engineering Development Array’s receiver temperature as a function of frequency. The Engineering Development Array is shown to be sky-noise limited over most of the frequency range measured between 60 and 240 MHz. By using the Engineering Development Array in interferometric mode with the Murchison Widefield Array, we used calibrated visibilities to measure the absolute sensitivity of the array. The measured array sensitivity matches very well with a model based on the array layout and measured receiver temperature. The results demonstrate the practicality and feasibility of using Murchison Widefield Array-style precursor technology for Square Kilometre Array-scale stations. The modular architecture of the Engineering Development Array allows upgrades to the array to be rolled out in a staged approach. Future improvements to the Engineering Development Array include replacing the second stage beamformer with a fully digital system, and to transition to using RF-over-fibre for the signal output from first stage beamformers.