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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.
OBJECTIVES/SPECIFIC AIMS: By combining clinical knowledge of hoarding disorder (HD) with qualitative methods from cultural anthropology, we hope to build a patient-centered approach that will allow us to better understand the clinician perspectives on patient motivations and explanatory models of individuals with HD, and improve treatment outcomes. We describe the ways that these methodologies are productively merged in this project as a result of TL1 collaboration, and present a preliminary picture of methodological and theoretical issues uncovered as part of this processes. We further describe the analytical methods used for this project, and explore issues raised through the combination of psychological and anthropological data and insights. METHODS/STUDY POPULATION: This study represents an attempt to combine the qualitative methodologies of cultural anthropology with the clinical knowledge of psychology and psychiatry in order to better understand gaps between provider and patient beliefs and knowledge about hoarding disorder. This study will present preliminary methodological issues arising from interviews with hoarding experts. RESULTS/ANTICIPATED RESULTS: This study will discuss preliminary issues including shared language, strengths and limitations of both disciplines, and factors for consideration when combining these disparate methodologies. It will close with recommendations for consideration when moving forward with similar collaborations. DISCUSSION/SIGNIFICANCE OF IMPACT: This project seeks to unite psychological and social factors that may contribute to the lived experience of individuals with HD in order to better understand the way that HD is manifested. It also unites disparate methodologies to provide us with a more holistic and complete picture of the experience of HD. While HD has been studied within psychiatry, it has never been assessed using the qualitative methods of anthropology. These methods provide the possibility of expanding knowledge about the ways that this disorder is experienced by individuals and their families, and potentially impacted by shared beliefs and cultures. Furthermore, qualitative data of this nature provides a patient perspective on the experience of HD as a psychiatric illness. This patient perspective can be used to better inform treatment, improve patient outcomes, and to allow providers and researchers to gain a fuller understanding of this complex population.
OBJECTIVES/SPECIFIC AIMS: More men than women develop urinary stones and their prevalence alters in women with menopause suggesting a steroidal influence. In men the incidence of stones is highest during July and August suggesting that environmental factors such as Vitamin D (VitD), a steroid, may affect stone formation. Previous studies have found differences in the development of stones between men and women; however, the reasons for sex differences in stone formation and type remain unclear. METHODS/STUDY POPULATION: We examined VitD levels in men and women (n = 18,753) that had no diseases based on a lack of an ICD-9 or ICD-10 code in their electronic medical record. We found that normal, healthy women had significantly higher levels of sera VitD compared to men (p = 6x10-6). We then examined whether sex differences existed for key endpoints/data from the Mayo Clinic Urinary Stone Disease (USD) Registry, which has around 1,600 urinary stone patients that are well-phenotyped according to sex, age and stone type. RESULTS/ANTICIPATED RESULTS: Control women were found to have higher sera VitD levels than men, but the sex difference no longer exists in kidney stone disease patients. When we further separated by race, we found that differences in VitD levels reappeared; this suggests that race also plays a role in sera VitD variances. DISCUSSION/SIGNIFICANCE OF IMPACT: We are developing a disease severity score, which we will use to correlate to sera VitD levels in patients according to sex, age and race. Future analyses will take into account whether subjects had VitD and calcium supplementation. This project begins to explore the mechanism behind the sex differences known to exist in urinary stone disease, which is critically needed to provide improved diagnosis and therapy for this debilitating disease.
Studies were conducted to determine the tolerance of sweetpotato and Palmer amaranth control to a premix of flumioxazin and pyroxasulfone pretransplant (PREtr) followed by (fb) irrigation. Greenhouse studies were conducted in a factorial arrangement of four herbicide rates (flumioxazin/pyroxasulfone PREtr at 105/133 and 57/72 g ai ha–1, S-metolachlor PREtr 803 g ai ha–1, nontreated) by three irrigation timings [2, 5, and 14 d after transplanting (DAP)]. Field studies were conducted in a factorial arrangement of seven herbicide treatments (flumioxazin/pyroxasulfone PREtr at 40/51, 57/72, 63/80, and 105/133 g ha–1, 107 g ha–1 flumioxazin PREtr fb 803 g ha–1S-metolachlor 7 to 10 DAP, and season-long weedy and weed-free checks) by three 1.9-cm irrigation timings (0 to 2, 3 to 5, or 14 DAP). In greenhouse studies, flumioxazin/pyroxasulfone reduced sweetpotato vine length and shoot and storage root fresh biomass compared to the nontreated check and S-metolachlor. Irrigation timing had no influence on vine length and root fresh biomass. In field studies, Palmer amaranth control was≥91% season-long regardless of flumioxazin/pyroxasulfone rate or irrigation timing. At 38 DAP, sweetpotato injury was≤37 and≤9% at locations 1 and 2, respectively. Visual estimates of sweetpotato injury from flumioxazin/pyroxasulfone were greater when irrigation timing was delayed 3 to 5 or 14 DAP (22 and 20%, respectively) compared to 0 to 2 DAP (7%) at location 1 but similar at location 2. Irrigation timing did not influence no.1, jumbo, or marketable yields or root length-to-width ratio. With the exception of 105/133 g ha–1, all rates of flumioxazin/pyroxasulfone resulted in marketable sweetpotato yield and root length-to-width ratio similar to flumioxazin fb S-metolachlor or the weed-free checks. In conclusion, flumioxazin/pyroxasulfone PREtr at 40/51, 57/72, and 63/80 g ha–1 has potential for use in sweetpotato for Palmer amaranth control without causing significant crop injury and yield reduction.
Field studies were conducted in 2015 and 2016 in North Carolina to determine the response of ‘Covington’ and ‘Murasaki-29’ sweetpotato cultivars to four rates of linuron (420, 560, 840, and 1,120 g ai ha–1) alone or with S-metolachlor (803 g ai ha–1) applied 7 or 14 d after transplanting (DAP). Injury (chlorosis/necrosis and stunting) to both cultivars was greater when linuron was applied with S-metolachlor as compared to linuron applied alone. Herbicide application at 14 DAP caused greater injury (chlorosis/necrosis and stunting) to both cultivars than when applied at 7 DAP. At 4 wk after treatment (WAT), stunting of Covington and Murasaki-29 (hereafter Murasaki) from linuron at 420 to 1,120 g ha–1 increased from 27% to 50% and 25% to 53%, respectively. At 7 or 8 WAT, crop stunting of 8% or less and 0% was observed in Covington and Murasaki, respectively, regardless of application rate and timing. Murasaki root yields were similar in the linuron alone or with S-metolachlor treatments, and were lower than the nontreated check. In 2016, no. 1 and marketable sweetpotato yields of Covington were similar for the nontreated check, linuron alone, or linuron plus S-metolachlor treatments, but not in 2015. Decreases in no. 1 and marketable root yields were observed when herbicides were applied 14 DAP compared to 7 DAP for Covington in 2015 and for Murasaki in both years. No. 1 and marketable yields of Covington were similar for 420 to 1,120 g ha–1 linuron and nontreated check except marketable root yields in 2015. No. 1 and marketable sweetpotato yields of Murasaki decreased as application rates increased.
Treatment for hoarding disorder is typically performed by mental health professionals, potentially limiting access to care in underserved areas.
We aimed to conduct a non-inferiority trial of group peer-facilitated therapy (G-PFT) and group psychologist-led cognitive–behavioural therapy (G-CBT).
We randomised 323 adults with hording disorder 15 weeks of G-PFT or 16 weeks of G-CBT and assessed at baseline, post-treatment and longitudinally (≥3 months post-treatment: mean 14.4 months, range 3–25). Predictors of treatment response were examined.
G-PFT (effect size 1.20) was as effective as G-CBT (effect size 1.21; between-group difference 1.82 points, t = −1.71, d.f. = 245, P = 0.04). More homework completion and ongoing help from family and friends resulted in lower severity scores at longitudinal follow-up (t = 2.79, d.f. = 175, P = 0.006; t = 2.89, d.f. = 175, P = 0.004).
Peer-led groups were as effective as psychologist-led groups, providing a novel treatment avenue for individuals without access to mental health professionals.
Declaration of interest
C.A.M. has received grant funding from the National Institutes of Health (NIH) and travel reimbursement and speakers’ honoraria from the Tourette Association of America (TAA), as well as honoraria and travel reimbursement from the NIH for serving as an NIH Study Section reviewer. K.D. receives research support from the NIH and honoraria and travel reimbursement from the NIH for serving as an NIH Study Section reviewer. R.S.M. receives research support from the National Institute of Mental Health, National Institute of Aging, the Hillblom Foundation, Janssen Pharmaceuticals (research grant) and the Alzheimer's Association. R.S.M. has also received travel support from the National Institute of Mental Health for Workshop participation. J.Y.T. receives research support from the NIH, Patient-Centered Outcomes Research Institute and the California Tobacco Related Research Program, and honoraria and travel reimbursement from the NIH for serving as an NIH Study Section reviewer. All other authors report no conflicts of interest.
The acoustics of a straight annular lined duct containing a swirling mean flow is considered. The classical Ingard–Myers impedance boundary condition is shown not to be correct for swirling flow. By considering behaviour within the thin boundary layers at the duct walls, the correct impedance boundary condition for an infinitely thin boundary layer with swirl is derived, which reduces to the Ingard–Myers condition when the swirl is set to zero. The correct boundary condition contains a spring-like term due to centrifugal acceleration at the walls, and consequently has a different sign at the inner (hub) and outer (tip) walls. Examples are given for mean flows relevant to the interstage region of aeroengines. Surface waves in swirling flows are also considered, and are shown to obey a more complicated dispersion relation than for non-swirling flows. The stability of the surface waves is also investigated, and as in the non-swirling case, one unstable surface wave per wall is found.
To validate a newly introduced cartilage rim augmented temporalis fascia tympanoplasty technique by statistically comparing it with the morphological and audiological outcomes of traditional temporalis fascia tympanoplasty.
A retrospective comparative study was conducted on 115 patients who underwent tympanoplasty during 2013 and 2015. Fifty-eight patients underwent temporalis fascia tympanoplasty and 57 underwent cartilage rim augmented fascia tympanoplasty.
In the cartilage fascia group, graft healing was achieved in 94.7 per cent of cases; in the temporalis fascia group, the graft take-up rate was 70 per cent. In those with a normal ossicular chain, the post-operative air–bone gap was within 20 dB in 92.6 per cent of cartilage fascia group cases and in 69.7 per cent of the temporalis fascia group cases, which was a statistically significant difference. Among the defective ossicular chain cases, the post-operative air–bone gap was within 20 dB in 76.9 per cent in the cartilage fascia group, as against 57.1 per cent in the temporalis fascia group.
Cartilage rim augmented temporalis fascia tympanoplasty has a definite advantage over the temporalis fascia technique in terms of superior graft take up and statistically significant hearing gain in those with normal ossicular mobility.
This paper gives a modified Myers boundary condition in swirling inviscid flow, which differs from the standard Myers boundary condition by assuming a small but non-zero boundary layer thickness. The new boundary condition is derived and is shown to have the correct quadratic error behaviour with boundary layer thickness and also to agree with previous results when the swirl is set to zero. The boundary condition is initially derived for swirling flow with constant azimuthal velocity, but easily extends to radially varying swirling flow, with terms depending on the boundary layer model. The modified Myers boundary condition is then given in the time domain rather than in the frequency domain. The effect of the boundary layer profile is then considered, and shown to be small compared to the boundary layer thickness. The boundary condition is then used to analyse the eigenmodes and Green’s function in a realistic flow. Modelling the thickness of the boundary layer properly is shown to be essential in order to get accurate results.
The unique phenotypic and genetic aspects of obsessive-compulsive (OCD) and attention-deficit/hyperactivity disorder (ADHD) among individuals with Tourette syndrome (TS) are not well characterized. Here, we examine symptom patterns and heritability of OCD and ADHD in TS families.
OCD and ADHD symptom patterns were examined in TS patients and their family members (N = 3494) using exploratory factor analyses (EFA) for OCD and ADHD symptoms separately, followed by latent class analyses (LCA) of the resulting OCD and ADHD factor sum scores jointly; heritability and clinical relevance of the resulting factors and classes were assessed.
EFA yielded a 2-factor model for ADHD and an 8-factor model for OCD. Both ADHD factors (inattentive and hyperactive/impulsive symptoms) were genetically related to TS, ADHD, and OCD. The doubts, contamination, need for sameness, and superstitions factors were genetically related to OCD, but not ADHD or TS; symmetry/exactness and fear-of-harm were associated with TS and OCD while hoarding was associated with ADHD and OCD. In contrast, aggressive urges were genetically associated with TS, OCD, and ADHD. LCA revealed a three-class solution: few OCD/ADHD symptoms (LC1), OCD & ADHD symptoms (LC2), and symmetry/exactness, hoarding, and ADHD symptoms (LC3). LC2 had the highest psychiatric comorbidity rates (⩾50% for all disorders).
Symmetry/exactness, aggressive urges, fear-of-harm, and hoarding show complex genetic relationships with TS, OCD, and ADHD, and, rather than being specific subtypes of OCD, transcend traditional diagnostic boundaries, perhaps representing an underlying vulnerability (e.g. failure of top-down cognitive control) common to all three disorders.
Orientation of striping caused by needle ice has been ascribed in the past to (1) wind direction during soil freezing, and (2) azimuth of the sun during thawing. Recent evidence supports the latter concept.
In the present work, we report the development of phase pure and highly crystalline stibnite Sb2S3 nanostructures by a surfactant-mediated hydrothermal method. Polyvinylpyrrolidone (PVP) as the surfactant has a striking effect on the assembly of nanorods into dumbbell shaped nanorod-bundles. While nanorods with high aspect ratio were formed in absence of the surfactant, dumbbell shaped nanorod bundles were obtained using the surfactant. The structural, morphological, and optical properties were examined by X-ray diffraction (XRD), Raman scattering, scanning electron microscopy (SEM), energy dispersive x-ray spectroscopy, x-ray photoelectron spectroscopy (XPS), and UV–visible spectrophotometer. Both XRD and Raman spectroscopy confirmed the formation of orthorhombic phase pure stibnite (Sb2S3). The ratio of Sb to S is found to be close to 2:3, corresponding to Sb2S3. The optical band gap varied in the range of 1.65–1.68 eV depending on the concentration of the surfactant.
Genetic–epidemiological studies that estimate the contributions of genetic factors to variation in tic symptoms are scarce. We estimated the extent to which genetic and environmental influences contribute to tics, employing various phenotypic definitions ranging between mild and severe symptomatology, in a large population-based adult twin-family sample.
In an extended twin-family design, we analysed lifetime tic data reported by adult mono- and dizygotic twins (n = 8323) and their family members (n = 7164; parents and siblings) from 7311 families in the Netherlands Twin Register. We measured tics by the abbreviated version of the Schedule for Tourette and Other Behavioral Syndromes. Heritability was estimated by genetic structural equation modeling for four tic disorder definitions: three dichotomous and one trichotomous phenotype, characterized by increasingly strictly defined criteria.
Prevalence rates of the different tic disorders in our sample varied between 0.3 and 4.5% depending on tic disorder definition. Tic frequencies decreased with increasing age. Heritability estimates varied between 0.25 and 0.37, depending on phenotypic definitions. None of the phenotypes showed evidence of assortative mating, effects of shared environment or non-additive genetic effects.
Heritabilities of mild and severe tic phenotypes were estimated to be moderate. Overlapping confidence intervals of the heritability estimates suggest overlapping genetic liabilities between the various tic phenotypes. The most lenient phenotype (defined only by tic characteristics, excluding criteria B, C and D of DSM-IV) rendered sufficiently reliable heritability estimates. These findings have implications in phenotypic definitions for future genetic studies.
The present study sought to explicate the time-course of posttraumatic stress (PTS)-related attentional bias to threat (ABT) by examining differences in attention bias variability (ABV; a measure which accounts for the temporal dynamics of ABT). A dot-probe task with four presentation durations was used to capture both subliminal and supraliminal stages of processing. Task stimuli consisted of neutral and threat images. Attentional control (AC) was examined as a moderator of the relationship between PTSD and ABV. At an experimental session, participants (PTSD = 11, trauma control = 18) completed questionnaires, a modified dot-probe task, and a stimulus-response task measuring AC. Individuals in the PTSD group exhibited greater ABV compared to trauma control participants. AC moderated this relationship, with participants with PTSD and poor AC exhibiting significantly greater ABV than trauma-exposed control participants with poor AC. These effects remained significant after accounting for traditionally calculated ABT scores and variability on trials for which only neutral stimuli were present, thus ensuring that the observed effects were specific to the presence of threat stimuli and not merely a function of general variability in response times. Findings implicate AC as a buffering mechanism against threat-related attentional dyscontrol among those with PTSD. Clinical implications will be discussed.
The aviation industry is dominated by the domain of heavier-than-air, fixed-wing, subsonic flight, and central to any design in this domain is the wing itself. One of the earliest debates in aviation still centres around the usefulness of the wing volume. On the one hand it is held that the wing, as an inevitable necessity, should provide the volume also for the payload. On the other, it is argued that more efficient wings do not even have sufficient volume for the entire wing structure. This work proposes precise definitions of the Wing Density and the Inflation Factor, two parameters that can quantitatively reflect the economic and technological trends in aviation. The wing volume of a hypothetical Ideal Wing is derived from the Operational Parameters of any given Flight Objective and compared to the volume requirement of that flight objective. We conclude that the dominant aircraft configuration of the future is likely to remain within the same family of the current dominant configuration, in conflict with some older predictions.
Anaplastic thyroid carcinoma is rare but carries a poor prognosis. Anaplastic thyroid carcinoma leads to tracheal compression, airway compromise and eventually death. Airway compromise, a particularly distressing symptom, can be palliated with tracheal stenting.
A retrospective case note analysis was conducted of patients diagnosed with anaplastic thyroid carcinoma between July 2003 and July 2013.
Twelve patients with anaplastic thyroid carcinoma were identified. Four patients underwent palliative tracheal stenting. Three patients had no dyspnoea at the time of stenting. Two stented patients subsequently developed dyspnoea secondary to stent migration; this was managed successfully with stent exchange. The other stented patient remained asymptomatic with regards to dyspnoea. All non-stented patients died with or from airway compromise.
Tracheal stenting is a relatively safe and effective method for palliation of distressing airway symptoms in patients with anaplastic thyroid carcinoma. Early prophylactic tracheal stenting in anaplastic thyroid carcinoma may be an effective option to prevent development of airway compromise as the disease progresses.
Peripheral vestibular function is commonly assessed using the Unterberger test. Patients are asked to march on the spot and their extent of rotation is recorded. The sensitivity of this test depends on an assessor accurately estimating the degree of rotation. This study therefore aimed to compare observer estimates with a smartphone application (DplusR Balance) that accurately records rotation.
Twenty-five participants were asked to estimate the degree of rotation in 10 successive Unterberger tests performed by a volunteer.
The average difference between estimated and application recorded extent of rotation was 30°.
Assessors poorly estimate the degree of rotation in this clinical test, to an extent sufficient to affect clinical interpretation and diagnosis. We recommend the use of this application or alternative methods to record the degree of rotation in patients.