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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.
Sleep disturbances are prevalent in cancer patients, especially those with advanced disease. There are few published intervention studies that address sleep issues in advanced cancer patients during the course of treatment. This study assesses the impact of a multidisciplinary quality of life (QOL) intervention on subjective sleep difficulties in patients with advanced cancer.
This randomized trial investigated the comparative effects of a multidisciplinary QOL intervention (n = 54) vs. standard care (n = 63) on sleep quality in patients with advanced cancer receiving radiation therapy as a secondary endpoint. The intervention group attended six intervention sessions, while the standard care group received informational material only. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS), administered at baseline and weeks 4 (post-intervention), 27, and 52.
The intervention group had a statistically significant improvement in the PSQI total score and two components of sleep quality and daytime dysfunction than the control group at week 4. At week 27, although both groups showed improvements in sleep measures from baseline, there were no statistically significant differences between groups in any of the PSQI total and component scores, or ESS. At week 52, the intervention group used less sleep medication than control patients compared to baseline (p = 0.04) and had a lower ESS score (7.6 vs. 9.3, p = 0.03).
Significance of results
A multidisciplinary intervention to improve QOL can also improve sleep quality of advanced cancer patients undergoing radiation therapy. Those patients who completed the intervention also reported the use of less sleep medication.
Additional crystallographic data are given for the recently reported mineral middlebackite, which has been described for discoveries at Iron Knob in South Australia and Passo di San Lugano near Trento, Italy. The material examined in the present study was from a third finding of the mineral, viz. from a quartz outcrop at Mooloo Downs Station in Western Australia within which it was co-located with the chemically- and structurally-related mineral moolooite, CuIIC2O4·nH2O, reported by Clarke and Williams (1986). In this study, the crystal structure was elucidated independently of the other studies using a combination of the a priori charge flipping and simulated annealing methods with synchrotron radiation diffraction (SRD) powder data. The principal crystal data for the Mooloo Downs material are: space group P21/c with lattice parameters a = 7.2659(18) Å, b = 5.7460(11) Å, c = 5.6806(11) Å, β = 104.588(3)°; Vc = 229.46(18) Å3; empirical formula CuII2C2O4(OH)2 with 2 formula units per unit cell; and calculated density = 3.605 g cm−3. The lattice parameters agree approximately with values given for the other studies, but not within the reported error estimates. The atom coordinates, interatomic distances, and angles for the Mooloo Downs material are compared with those from the other studies using single crystal data, with the values from all three studies agreeing approximately, but again not within the reported uncertainties. The crystal chemistry found for middlebackite received strong confirmation through the synthesis for the first time of di-copper oxalate di-hydroxide. Laboratory X-ray diffraction powder data for the synthetic form of the mineral from this study agree closely with the SRD data for the natural mineral.
Individual differences in cognitive responses to trauma may represent modifiable risk factors that could allow early identification, targeted early treatment and possibly prevention of chronic posttraumatic stress disorder (PTSD). Ehlers and Clark's cognitive model of PTSD suggests that negative appraisals, disjointed trauma memories, and unhelpful coping strategies maintain PTSD. These are thought to be influenced by cognitive processing during trauma. The aim of this study was to test this model prospectively with path analyses.
Participants (N = 828) were recruited from an emergency department following injury in a violent assault or road traffic collision and 700 participated in the 6-month assessments. Cognitive processing was assessed shortly after the event, negative appraisals, disjointed memories, and unhelpful coping strategies at 1 month, persistent PTSD symptom severity at 6 months, and early PTSD symptom severity at 2 weeks.
Cognitive variables, with trauma type and gender, explained 52% of the variance in PTSD symptom severity at 6 months. Including early symptom severity in the model did not explain more variance (53%). Early PTSD symptom severity, with trauma type and gender, only predicted 40%. Negative appraisals and disjointed memories predicted persistent symptom severity both directly and indirectly via unhelpful strategies. Peritraumatic processing predicted persistent symptom severity mainly indirectly. The effects of trauma type and gender were fully mediated by the cognitive factors.
The results are consistent with theoretically derived predictions and support cognitive factors as indicators of risk for chronic PTSD and as a target for the treatment and prevention of PTSD.
Moral cognition, by its very nature, stems from intuitions about what is good and bad, and these intuitions influence moral assessments outside of conscious awareness. However, because humans evolved a shared set of moral intuitions, and are compelled to justify their moral assessments as good and rational (even erroneously) to others, moral virtue and moral progress are still possible.
We determined how pasture and grazing management practices affected the number of days hay was fed to cattle by season. Data were collected from a survey of Tennessee cattle producers. Days of cattle on hay varied across seasons because of variations in forage production and weather. The number of days hay was fed to cattle varied with pasture-animal management practices such as rotating pastures, forage mixtures, and weed management strategies. Having mixtures of cool- and warm-season grasses reduced the number of days on hay in the winter, spring, and summer months indicating benefits from diversified forages.
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.
Endoscopic ear surgery is a technique that is growing in popularity. It has potential advantages in the low-resource setting for teaching and training, for the relative ease of transporting and storing the surgical equipment and for telemedicine roles. There may also be advantages to the patient, with reduced post-operative pain, facilitating the ability to complete procedures as out-patients.
Our Ear Trainer has previously been validated for headlight and microscope otology skills, including foreign body removal and ventilation tube insertion, in both the high- and low-resource setting. This study aimed to assess the Ear Trainer for similar training and assessment of endoscopic ear surgery skills in the low-resource setting. The study was conducted in Uganda on ENT trainees.
Despite a lack of prior experience with endoscopes, with limited practice time most participants showed improvements in: efficiency of instrument movement, steadiness of the camera view obtained, overall global rating of the task and performance time (faster task performance).
These results indicate that the Ear Trainer is a useful tool in the training and assessment of endoscopic ear surgery skills.
Prior work has robustly suggested that social processes in the neighborhood (i.e. informal social control, social cohesion, norms) influence child conduct problems (CP) and related outcomes, but has yet to consider how these community-level influences interact with individual-level genetic risk for CP. The current study sought to do just this, evaluating neighborhood-level social processes as etiologic moderators of child CP for the first time.
We made use of two nested samples of child and adolescent twins within the Michigan State University Twin Registry (MSUTR): 5649 families who participated in in the Michigan Twins Project (MTP) and 1013 families who participated in the Twin Study of Behavioral and Emotional Development (TBED-C). The neighborhood social processes of informal social control, social cohesion, and norms were assessed using neighborhood sampling techniques, in which residents of each twin family's neighborhood reported on the social processes in their neighborhood. Standard biometric GxE analyses evaluated the extent to which they moderated the etiology of CP.
The ‘no moderation’ model provided the best fit to the data in nearly all cases, arguing against neighborhood social processes as etiologic moderators of youth CP.
The neighborhood social processes evaluated here do not appear to exert their effects on child CP via etiologic moderation. The documented links between neighborhood social processes and child CP are thus likely to reflect a different etiologic process. Possibilities include environmental main effects of neighborhood social processes on child CP, or genotype-environment correlations.
The diurnal feeding patterns of dairy cows affects the 24 h robot utilisation of pasture-based automatic milking systems (AMS). A decline in robot utilisation between 2400 and 0600 h currently occurs in pasture-based AMS, as cow feeding activity is greatly reduced during this time. Here, we investigate the effect of a temporal variation in feed quality and quantity on cow feeding behaviour between 2400 and 0600 h as a potential tool to increase voluntary cow trafficking in an AMS at night. The day was allocated into four equal feeding periods (0600 to 1200, 1200 to 1800, 1800 to 2400 and 2400 to 0600 h). Lucerne hay cubes (CP = 19.1%, water soluble carbohydrate = 3.8%) and oat, ryegrass and clover hay cubes with 20% molasses (CP = 11.8%, water soluble carbohydrate = 10.7%) were offered as the ‘standard’ and ‘preferred’ (preference determined previously) feed types, respectively. The four treatments were (1) standard feed offered ad libitum (AL) throughout 24 h; (2) as per AL, with preferred feed replacing standard feed between 2400 and 0600 h (AL + P); (3) standard feed offered at a restricted rate, with quantity varying between each feeding period (20:10:30:60%, respectively) as a proportion of the (previously) measured daily ad libitum intake (VA); (4) as per VA, with preferred feed replacing standard feed between 2400 and 0600 h (VA + P). Eight non-lactating dairy cows were used in a 4 × 4 Latin square design. During each experimental period, treatment cows were fed for 7 days, including 3 days habituation and 4 days data collection. Total daily intake was approximately 8% greater (P < 0.001) for the AL and AL + P treatments (23.1 and 22.9 kg DM/cow) as compared with the VA and VA + P treatments (21.6 and 20.9 kg DM/cow). The AL + P and VA treatments had 21% and 90% greater (P < 0.001) dry matter intake (DMI) between 2400 and 0600 h, respectively, compared with the AL treatment. In contrast, the VA + P treatment had similar DMI to the VA treatment. Our experiment shows ability to increase cow feeding activity at night by varying feed type and quantity, though it is possible that a penalty to total DMI may occur using VA. Further research is required to determine if the implementation of variable feed allocation on pasture-based AMS farms is likely to improve milking robot utilisation by increasing cow feeding activity at night.
Overweight and obesity may increase risk of disease progression in men with prostate cancer, but there have been few studies of weight loss interventions in this patient group. In this study overweight or obese men treated for prostate cancer were randomised to a self-help diet and activity intervention with telephone-based dietitian support or a wait-list mini-intervention group. The intervention group had an initial group meeting, a supporting letter from their urological consultant, three telephone dietitian consultations at 4-week intervals, a pedometer and access to web-based diet and physical activity resources. At 12 weeks, men in both groups were given digital scales for providing follow-up weight measurements, and the wait-list group received a mini-intervention of the supporting letter, a pedometer and access to the web-based resources. Sixty-two men were randomised; fifty-four completed baseline and 12-week measurements, and fifty-one and twenty-seven provided measurements at 6 and 12 months, respectively. In a repeated-measures model, mean difference in weight change between groups (wait-list mini-intervention minus intervention) at 12 weeks was −2·13 (95 % CI −3·44, −0·82) kg (P = 0·002). At 12 months the corresponding value was −2·43 (95 % CI −4·50, −0·37) kg (P = 0·022). Mean difference in global quality of life score change between groups at 12 weeks was 12·3 (95 % CI 4·93, 19·7) (P = 0·002); at 12 months there were no significant differences between groups. Results suggest the potential of self-help diet and physical activity intervention with trained support for modest but sustained weight loss in this patient group.
Observation of the ion source generated background has been an area of focus during our routine analytical work. It is noted that the results of very-low-ratio samples are dependent upon the particular procedures for measurement using the present-day Cs+ sputter ion sources. When measured without excessive Cs+ fluxes and without interleafing with other higher-ratio samples and references, the accelerator mass spectrometry (AMS) sensitivity can be somewhat improved. In some cases, it appears possible to assess old radiocarbon (14C) samples to beyond the long-standing 60 kyr limit. A number of observational studies are made for the sole purpose of minimizing the final contamination to the rare isotopes that is generated within the ion source.
Background: Utilization of endovascular procedures in the perioperative management of patients undergoing transsphenoidal surgery is uncommon but plays a critical role in preventing and treating potentially life-threatening vascular complications. Methods: We performed a retrospective review of all patients over a 10-year period who underwent transsphenoidal surgery at two tertiary-care institutions and identified all pre-operative and post-operative endovascular procedures performed. Results: 18 perioperative endovascular procedures were performed including 9 pre- and 9 post-operative. Pre-operative procedures included balloon-test occlusion (n=4), aneurysm coiling (n=4), and parent artery occlusion (n=1). One aneurysm coiling was complicated by coil migration requiring coil retrieval with a snare device and one balloon-test occlusion was complicated by pituitary apoplexy. Pituitary apoplexy following balloon-test occlusion has not been reported and the potential pathophysiology is reviewed. Post-operative procedures included embolization for epistaxis (n=2) and embolization with or without parent artery sacrifice for carotid and anterior cerebral artery vascular injury (n=7). Arterial vascular injury was managed with coil embolization and/or with detachable balloons. Review of anatomical features predisposing to vascular injury are discussed. Conclusions: Patients undergoing transsphenoidal surgery should be managed with a multidisciplinary team ensuring that endovascular treatment options are made available during the perioperative period.