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Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders.
We used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific.
We identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001).
Our findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.
Crary Ice Rise formed after the Ross Ice Shelf re-grounded ~1 kyr BP. We present new ice-penetrating radar data from two systems operating at center frequencies of 7 and 750 MHz that confirm the ice rise is composed of a former ice shelf buried by subsequent accumulation. Stacks of englacial diffraction hyperbolas are present almost everywhere across the central ice rise and extend up to ~350 m above the bed. In many cases, bed reflections beneath the diffraction hyperbolas are obscured for distances up to 1 km. Waveform modeling indicates that the diffraction hyperbolas are likely caused by marine ice deposits in former basal crevasses and rifts. The in-filling of rifts and basal crevasses may have strengthened the connection between the ice rise and the surrounding ice shelf, which could have influenced local and regional ice dynamics. Three internal reflection horizons mark the upper limit of disturbed ice and diffraction hyperbolas in different sections of the ice rise, indicating at least three stages of flow stabilization across the ice rise. A surface lineation visible in MODIS imagery corresponds spatially to deepening and strong deformation of these layers, consistent with the characteristics of former grounding lines observed elsewhere in Antarctica.
ABSTRACT IMPACT: The potential to use vaginal pH as a low cost, non-invasive diagnostic test at the point of CIN2 diagnosis to predict worsening of cervical disease. OBJECTIVES/GOALS: We previously reported that persistence/progression of cervical intraepithelial neoplasia-2 (CIN2) was uncommon in women living with HIV (WLH) from the Women’s Interagency HIV Study (WIHS, now MWCCS). Here we examined additional factors that may influence CIN2 natural history. METHODS/STUDY POPULATION: A total of 337 samples from 94 WLH with a confirmed CIN2 diagnosis were obtained from the MWCCS. 42 cervicovaginal HPV types and 34 cervicovaginal cytokines/chemokines were measured at CIN2 diagnosis (94 samples) and 6-12 months prior to CIN2 diagnosis (79 samples). Covariates, including CD4 count and vaginal pH, were abstracted from core MWCCS visits. Logistic regression models were used to explore CIN2 regression (CIN1, normal) vs. persistence/progression (CIN2, CIN3). Log rank tests, Kaplan Meier method, and Cox regression modeling were used to determine CIN2 regression rates. RESULTS/ANTICIPATED RESULTS: The most prevalent HPV types were HPV54 (21.6%) and 53 (21.3%). 33 women (35.1%) had a subsequent CIN2/CIN3 diagnosis (median 12.5 years follow-up). Each additional hr-HPV type detected at the pre-CIN2 visit associated with increased odds of CIN2 persistence/progression (OR 2.27, 95% CI 1.15, 4.50). Higher vaginal pH (aOR 2.27, 95% CI 1.15, 4.50) and bacterial vaginosis (aOR 5.08, 95% CI 1.30, 19.94) at the CIN2 diagnosis visit associated with higher odds of CIN2 persistence/progression. Vaginal pH >4.5 at CIN2 diagnosis also associated with unadjusted time to CIN2 persistence/progression (log rank p=0.002) and a higher rate of CIN2 persistence/progression (adjusted hazard ratio [aHR] 3.37, 95% CI 1.26, 8.99). Cervicovaginal cytokine/chemokine levels were not associated with CIN2 persistence/progression. DISCUSSION/SIGNIFICANCE OF FINDINGS: We found relatively low prevalence of HPV16/18 in this cohort. Elevated vaginal pH at the time of CIN2 diagnosis may be a useful indicator of CIN2 persistence/progression and the rate of persistence/progression.
Our qualitative descriptive study compared how older patients and their informal caregivers experienced the care transition from acute care or rehabilitation to home. We recruited patients 65 years of age or older, or their informal caregivers, from in-patient units within acute care hospitals and rehabilitation facilities to participate in semi-structured interviews. We identified emergent themes via thematic analysis. In all, 16 patients and four patient caregivers participated. Across all care settings, caregivers were integral in facilitating the transition as well as experiencing variable discharge preparation, health care providers’ optimizing transitions, and missed care and medication discrepancies at transition points. Orthopedic and rehabilitation patients more commonly voiced prior transition experiences in discharge preparation, including having to unexpectedly coordinate and wait for outpatient services. Differing responses between acute care and orthopedic settings suggest that transitional care practices and policies favor an individualized approach that considers patients’ previous experiences, needs, and care expectations.
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.
To explore how a palliative approach to care is operationalized in primary care, through the description of clinical practices used by primary care clinicians to identify and care for patients with progressive life-limiting illness (PLLI).
Increasing numbers of people are living with PLLI but are often not recognized as needing a palliative approach to care. To meet growing needs, generalists such as family physicians will need to adopt a palliative approach to care in their own setting. Practical descriptions of a palliative approach in non-specialist settings have been lacking.
We conducted a qualitative descriptive study design using in-depth semi-structured interviews with 11 key informant participants (6 physicians, 3 nurse practitioners, 1 registered nurse, and 1 registered practical nurse) known to be providing comprehensive care to patients with PLLI in family practices in Ontario, Canada. We asked about their approach to identifying patients with PLLI and the strategies used in their care. We employed content analysis to develop themes.
Participants identified patients by functional decline, change in needs, increased acuity, and the specifics of a condition/diagnosis. Care strategies included concretizing commitment to care, eliciting goals of care, shifting care to the home, broadening team members including leveraging the support of family and community resources, and shifting to a ‘proactive’ approach involving increased follow-up, flexibility, and intensity.
Primary care providers articulated strategies for identifying and providing care to patients with PLLI that illuminate an upstream approach tailored to their setting.
GPS measurements of tidal modulation of ice flow and seismicity within the grounding zone of Beardmore Glacier show that tidally induced fluctuations of horizontal flow are largest near the grounding line and decrease downstream. Seismic activity is continuous, but peaks occur on falling and rising tides. Beamforming methods reveal that most seismic events originate from two distinct locations, one on the grid-north side of the grounding zone, and one on the grid-south side. The broad pattern of deformation generated as Beardmore Glacier merges with the Ross Ice Shelf results in net extension along the grid-north side of the grounding zone and net compression along the grid-south side. During falling tides, seismic activity peaks on both sides because of increased vertical flexure across the grounding line. During rising tides, seismic activity in the region of extension on the grid-north side is relatively low because the tidal influence on both horizontal strain rate and vertical flexure is small. On the grid-south side during rising tides, however, tidally induced horizontal strain rates promote increased seismicity in regions of long-term compressional flow paths. Our study highlights how concurrent geodetic and seismic measurements provide insight into grounding-zone mechanics and their influence on ice-shelf buttressing.
Young women aged 16–24 are at high risk of common mental disorders (CMDs), but the risk during pregnancy is unclear.
To compare the population prevalence of CMDs in pregnant women aged 16–24 with pregnant women ≥25 years in a representative cohort, hypothesising that younger women are at higher risk of CMDs (depression, anxiety disorders, post-traumatic stress disorder, obsessive–compulsive disorder), and that this is associated with low social support, higher rates of lifetime abuse and unemployment.
Analysis of cross-sectional baseline data from a cohort of 545 women (of whom 57 were aged 16–24 years), attending a South London maternity service, with recruitment stratified by endorsement of questions on low mood, interviewed with the Structured Clinical Interview DSM-IV-TR.
Population prevalence estimates of CMDs were 45.1% (95% CI 23.5–68.7) in young women and 15.5% (95% CI 12.0–19.8) in women ≥25, and for ‘any mental disorder’ 67.2% (95% CI 41.7–85.4) and 21.2% (95% CI 17.0–26.1), respectively. Young women had greater odds of having a CMD (adjusted odds ratio (aOR) = 5.8, 95% CI 1.8–18.6) and CMDs were associated with living alone (aOR = 3.0, 95% CI 1.1–8.0) and abuse (aOR = 1.5, 95% CI 0.8–2.8).
Pregnant women between 16 and 24 years are at very high risk of mental disorders; services need to target resources for pregnant women under 25, including those in their early 20s. Interventions enhancing social networks, addressing abuse and providing adequate mental health treatment may minimise adverse outcomes for young women and their children.
Falls prevention strategies can only be effective in reducing falls amongst older people if they are adopted and enacted in their daily lives. There is limited evidence identifying what older people in residential aged care (RAC) homes understand about falls and falls prevention, or what may limit or enable their adoption of strategies. This study was conducted in two countries and explored older people's knowledge and awareness of falls and their preferences, opportunities and motivation to undertake falls prevention strategies. A cross-sectional survey was administered to participants (N = 70) aged 65 years and over, living in six RAC homes in Perth, Australia and six RAC homes in Swansea, Wales, United Kingdom. Participants had limited knowledge about intrinsic falls risk factors and strategies to address these and frequently expressed self-blame regarding falling. Almost all (N = 67, 95.7%) participants felt highly motivated to maintain their current functional mobility and independence in everyday tasks. Key preferences for receiving falls prevention messages favoured a positive approach promoting wellness and independence (N = 41, 58.6%) via pictorial posters or brochures (N = 37, 52.9%) and small group discussions preferably with demonstrations (N = 18, 25.7%). Findings from this study may assist organisations and staff to more effectively engage with older people living in RAC about falls prevention and design targeted resources to address the motivations and preferences of this population.
There is limited evidence on the prevalence and identification of antenatal mental disorders.
To investigate the prevalence of mental disorders in early pregnancy and the diagnostic accuracy of depression-screening (Whooley) questions compared with the Edinburgh Postnatal Depression Scale (EPDS), against the Structured Clinical Interview DSM-IV-TR.
Cross-sectional survey of women responding to Whooley questions asked at their first antenatal appointment. Women responding positively and a random sample of women responding negatively were invited to participate.
Population prevalence was 27% (95% CI 22–32): 11% (95% CI 8–14) depression; 15% (95% CI 11–19) anxiety disorders; 2% (95% CI 1–4) obsessive–compulsive disorder; 0.8% (95% CI 0–1) post-traumatic stress disorder; 2% (95% CI 0.4–3) eating disorders; 0.3% (95% CI 0.1–1) bipolar disorder I, 0.3% (95% CI 0.1–1%) bipolar disorder II; 0.7% (95% CI 0–1) borderline personality disorder. For identification of depression, likelihood ratios were 8.2 (Whooley) and 9.8 (EPDS). Diagnostic accuracy was similar in identifying any disorder (likelihood ratios 5.8 and 6).
Endorsement of Whooley questions in pregnancy indicates the need for a clinical assessment of diagnosis and could be implemented when maternity professionals have been appropriately trained on how to ask the questions sensitively, in settings where a clear referral and care pathway is available.
Declaration of interest
L.M.H. chaired the National Institute for Health and Care Excellence CG192 guidelines development group on antenatal and postnatal mental health in 2012–2014.
The distribution of temporal scale-dependent streamwise velocity increments is investigated in turbulent boundary layer flows at laboratory and atmospheric Reynolds numbers, using the St. Anthony Falls Laboratory wind tunnel and the Surface Layer Turbulence and Environmental Science Test dataset, respectively. The third-order moments of velocity increments, or asymmetry index
, is computed for varying wall distance
and time scale separation
, where it was observed to leave a robust, distinct signature in the form of a hump, independent of Reynolds number and located across the inertial range. The hump is observed in wall region limited to
, with a tendency to shift towards smaller time scales as the surface is approached (
). Comparing the two datasets, the hump, and its location, are found to obey inner wall scaling and is regarded as a genuine feature of the canonical turbulent boundary layer. The magnitude cumulant analysis of the scale-dependent velocity increments further reveals that intermittency is also enhanced near the wall, in the same flow region where the asymmetry signature was observed. The combination of asymmetry and intermittency is inferred to point at non-local energy transfer and scale coupling across a range of scales. From a turbulent structure perspective, such non-local energy transfer can be seen as the result of strong scale-interaction processes between outer scale motions in the logarithmic layer impacting and distorting smaller scales at the wall, through abrupt energy transfer across scales bypassing the typical energy cascade of the inertial range.
Thirty years ago, large-scale natural disasters were considered to be low-probability, high-consequence events. Between 1970 and the mid 1980s, annual insured losses from natural disasters world-wide (including forest fires) were only in the $3–$4 billion range. Hurricane Hugo, which made landfall in Charleston, South Carolina, on September 22, 1989, was the first natural disaster in the United States to inflict more than $1 billion of insured losses. Times have changed.
Economic and insured losses from great natural catastrophes such as earthquakes, hurricanes, and floods have increased significantly in recent years. According to Munich Re (2013), economic losses from natural catastrophes increased from $528 billion (1981–1990), to $1,197 billion (1991–2000), to $1,213 billion (2001–2010). During the past ten years, the losses were principally due to hurricanes and resulting storm surge occurring in 2004, 2005, and 2008. Figure 8.1 depicts the evolution of the direct economic losses and the insured portion from great natural disasters over the period 1980–2012. Given the massive economic losses from the March 2011 earthquake and resulting tsunami in Japan, the year 2011 was the most costly year on record for disasters globally: $370 billion (Swiss Re, 2011).
We reported a mammalian cell-imaging paradigm to study the cellular response to single-walled carbon nanotubes (SWCNTs). Chinese Hamster Ovarian (CHO) cells were exposed to SWCNTs resuspended in physiologically compatible buffer (phosphate buffered saline, PBS), at concentrations ranging from 0 to 50 μg/mL. Upon exposure, we optically imaged the cells in order to (1) visualize the accumulation SWCNTs in cells in real-time; (2) qualitatively and quantitatively assess the morphological changes associated with cellular stress in the presence of SWCNTs; and (3) serially quantify cell survival with highly sensitive bioluminescence-based imaging. Our results showed that the cell survival obtained from optical imaging agreed with that from CellTiter-Glo (CTG) luminescence viability assay. Acute compromise in the CHO cell’s survival rate was observed under high concentrations of SWCNT exposure. The cellular response as a function of SWCNT concentrations, and exposure time was further investigated.