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This article examines candidate emails from the 2016–17 Conservative Party of Canada leadership race to explore how candidates communicated with party supporters on issues of moral traditionalism (for example, abortion and sexuality diversity) and minority religious accommodation. We find that the level of public support for a given policy position shaped how overtly candidates signalled their views, with those supporting moral traditionalism or restrictions on religious minorities tending to express their views covertly and vice versa. Message overtness also changed following the deadline for new members to join the party before the vote. This article marks the first systematic study of how party leadership candidates attempt to solicit support from particular party factions and how candidates’ appeals evolve throughout a campaign. The results also show that the high-profile debate around minority religious accommodation during the leadership race did not displace contestation between candidates over issues such as sexual or reproductive rights.
Individuals with depression often do not respond to medication or psychotherapy. Radically open dialectical behaviour therapy (RO DBT) is a new treatment targeting overcontrolled personality, common in refractory depression.
To compare RO DBT plus treatment as usual (TAU) for refractory depression with TAU alone (trial registration: ISRCTN 85784627).
RO DBT comprised 29 therapy sessions and 27 skills classes over 6 months. Our completed randomised trial evaluated RO DBT for refractory depression over 18 months in three British secondary care centres. Of 250 adult participants, we randomised 162 (65%) to RO DBT. The primary outcome was the Hamilton Rating Scale for Depression (HRSD), assessed masked and analysed by treatment allocated.
After 7 months, immediately following therapy, RO DBT had significantly reduced depressive symptoms by 5.40 points on the HRSD relative to TAU (95% CI 0.94–9.85). After 12 months (primary end-point), the difference of 2.15 points on the HRSD in favour of RO DBT was not significant (95% CI –2.28 to 6.59); nor was that of 1.69 points on the HRSD at 18 months (95% CI –2.84 to 6.22). Throughout RO DBT participants reported significantly better psychological flexibility and emotional coping than controls. However, they reported eight possible serious adverse reactions compared with none in the control group.
The RO DBT group reported significantly lower HRSD scores than the control group after 7 months, but not thereafter. The imbalance in serious adverse reactions was probably because of the controls' limited opportunities to report these.
Declaration of interest
Six of the 16 authors have received royalties or fees for RO DBT. R.J.H. is co-owner and director of Radically Open Ltd, the RO DBT training and dissemination company. D.K. reports grants outside the submitted work from NIHR. T.R.L. receives royalties from New Harbinger Publishing for sales of RO DBT treatment manuals, speaking fees from Radically Open Ltd and a grant outside the submitted work from the Medical Research Council. He was codirector of Radically Open Ltd between November 2014 and May 2015 and is married to Erica Smith-Lynch, the principal shareholder and one of two current directors of Radically Open Ltd. H.O’M. reports personal fees from the Charlie Waller Institute and Improving Access to Psychological Therapy. S.C.R. provides RO DBT supervision through S C Rushbrook Ltd. I.T.R. reports grants outside the submitted work from NIHR and Health & Care Research Wales. M.St. reports personal fees from British Isles DBT Training, Stanton Psychological Services Ltd, and Taylor & Francis Ltd. M.Sw. reports personal fees from British Isles DBT Training, Guilford Press, Oxford University Press and Taylor & Francis Ltd. B.W. was codirector of Radically Open Ltd between November 2014 and February 2015.
The late Pleistocene–early Holocene archaeological record of the interior Pacific Northwest is dominated by what has been regionally referred to as the Western Stemmed Tradition (WST). While various efforts have attempted to clarify the chronology of this tradition, these have largely focused on data from the Great Basin and have been disproportionately preoccupied with establishing the beginning of the tradition due to its temporal overlap with Clovis materials. Specifically focusing on the Columbia Plateau, we apply a series of Bayesian chronological models to create concise estimates of the most likely beginning, end, and span of the WST. We then further explore its chronology by modeling its temporal span under various parameters and criteria so as to better identify places in the chronology that need further work and those that are robust regardless of data iteration. Our analysis revealed four major findings: (1) WST conservatively dates between 13,000 and 11,000 cal BP, likely extending to ~13,500 cal BP; (2) the most problematic period for WST is its termination; (3) the WST is incredibly long-lived compared to roughly contemporary Paleoindian traditions; and (4) the WST was seemingly unaffected by the onset of the Younger Dryas.
Inadequate protein quality may be a risk factor for poor growth. To examine the effect of a macronutrient–micronutrient supplement KOKO Plus (KP), provided to infants from 6 to 18 months of age, on linear growth, a single-blind cluster-randomised study was implemented in Ghana. A total of thirty-eight communities were randomly allocated to receive KP (fourteen communities, n 322), a micronutrient powder (MN, thirteen communities, n 329) and nutrition education (NE, eleven communities, n 319). A comparison group was followed cross-sectionally (n 303). Supplement delivery and morbidity were measured weekly and anthropometry monthly. NE education was provided monthly. Baseline, midline and endline measurements at 6, 12 and 18 months included venous blood draws, diet, anthropometry, morbidity, food security and socio-economics. Length-for-age Z-score (LAZ) was the primary outcome. Analyses were intent-to-treat using mixed-effects regressions adjusted for clustering, sex, age and baseline. No differences existed in mean LAZ scores at endline (−1·219 (sd 0·06) KP, −1·211 (sd 0·03) MN, −1·266 (sd 0·03) NE). Acute infection prevalence was lower in the KP than NE group (P = 0·043). Mean serum Hb was higher in KP infants free from acute infection (114·02 (sd 1·87) g/l) than MN (107·8 (sd 2·5) g/l; P = 0·047) and NE (108·8 (sd 0·99) g/l; P = 0·051). Compliance was 84·9 % (KP) and 87·2 % (MN) but delivery 60 %. Adjusting for delivery and compliance, LAZ score at endline was significantly higher in the KP v. MN group (+0·2 LAZ; P = 0·026). A macro- and micronutrient-fortified supplement KP reduced acute infection, improved Hb and demonstrated a dose–response effect on LAZ adjusting consumption for delivery.
One generation's experience of childhood maltreatment is associated with that of the next. However, whether this intergenerational transmission is specific to distinct forms of maltreatment and what factors may contribute to its continuity remains unclear. Borderline personality pathology is predicted by childhood maltreatment and characterized by features (e.g., dysregulated emotion, relationship instability, impulsivity, and inconsistent appraisals of others) that may contribute to its propagation. Among 364 older adults and 573 of their adult children (total n = 937), self-reported exposure to distinct forms of childhood maltreatment (i.e., emotional, physical, and sexual abuse, and emotional and physical neglect as assessed by the Childhood Trauma Questionnaire) showed homotypic and heterotypic associations across generations with little evidence that latent factors unique to specific forms of maltreatment show generational continuity. General nonspecific indices of childhood maltreatment showed evidence of intergenerational transmission after accounting for demographic factors and parent socioeconomic status (b = 0.126, p = 9.21 × 10−4). This continuity was partially mediated by parental borderline personality pathology (assessed longitudinally through a variety of measures and sources, indirect effect: b = 0.031, 95% confidence interval [0.003, 0.060]). The intergenerational continuity of childhood maltreatment may largely represent general risk for nonspecific maltreatment that may, in part, be propagated by borderline personality pathology and/or shared risk factors.
Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.
Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.
CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.
Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.
Workforce shortages in psychiatry are common worldwide. The international literature provides insights into factors influencing decisions to train in psychiatry but is predominately survey based. This national cohort study aimed to identify the characteristics of doctors who were most likely to apply to psychiatry training programmes. The sample comprised doctors who entered UK medical schools in 2007/8 and who made first-time specialty training applications in 2015. The association between application to psychiatry and doctors' sociodemographic and educational characteristics was examined using multivariable logistic regression.
Those most likely to apply were White, privately educated older doctors with below average performance at medical school.
To reduce workforce shortages, psychiatry must make itself more attractive to all doctors, especially those from underrepresented groups such as state-educated Black and minority ethnic individuals. Otherwise, national policies to widen participation in the study of medicine by such groups may exacerbate the current recruitment crisis.
The shape gradient quantifies the change in some figure of merit resulting from differential perturbations to a shape. Shape gradients can be applied to gradient-based optimization, sensitivity analysis and tolerance calculation. An efficient method for computing the shape gradient for toroidal three-dimensional magnetohydrodynamic (MHD) equilibria is presented. The method is based on the self-adjoint property of the equations for driven perturbations of MHD equilibria and is similar to the Onsager symmetry of transport coefficients. Two versions of the shape gradient are considered. One describes the change in a figure of merit due to an arbitrary displacement of the outer flux surface; the other describes the change in the figure of merit due to the displacement of a coil. The method is implemented for several example figures of merit and compared with direct calculation of the shape gradient. In these examples the adjoint method reduces the number of equilibrium computations by factors of
is the number of parameters used to describe the outer flux surface or coil shapes.
To Investigate the peripheral inflammatory profile in patients with mild cognitive impairment (MCI) from three subgroups – probable Lewy body disease (probable MCI-LB), possible Lewy body disease, and probable Alzheimer’s disease (probable MCI-AD) – as well as associations with clinical features.
Memory clinics and dementia services.
Patients were classified based on clinical symptoms as probable MCI-LB (n = 38), possible MCI-LB (n = 18), and probable MCI-AD (n = 21). Healthy comparison subjects were recruited (n = 20).
Ten cytokines were analyzed from plasma samples: interferon (IFN)-gamma, interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, and tumor necrosis factor (TNF)-alpha. C-reactive protein levels were investigated.
There was a higher level of IL-10, IL-1beta, IL-2, and IL-4 in MCI groups compared to the healthy comparison group (p < 0.0085). In exploratory analyses to understand these findings, the MC-AD group lower IL-1beta (p = 0.04), IL-2 (p = 0.009), and IL-4 (p = 0.012) were associated with increasing duration of memory symptoms, and in the probable MCI-LB group, lower levels of IL-1beta were associated with worsening motor severity (p = 0.002). In the possible MCI-LB, longer duration of memory symptoms was associated with lower levels of IL-1beta (p = 0.003) and IL-4 (p = 0.026).
There is increased peripheral inflammation in patients with MCI compared to healthy comparison subjects regardless of the MCI subtype. These possible associations with clinical features are consistent with other work showing that inflammation is increased in early disease but require replication. Such findings have importance for timing of putative therapeutic strategies aimed at lowering inflammation.
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.
Dopaminergic imaging has high diagnostic accuracy for dementia with Lewy bodies (DLB) at the dementia stage. We report the first investigation of dopaminergic imaging at the prodromal stage.
We recruited 75 patients over 60 with mild cognitive impairment (MCI), 33 with probable MCI with Lewy body disease (MCI-LB), 15 with possible MCI-LB and 27 with MCI with Alzheimer's disease. All underwent detailed clinical, neurological and neuropsychological assessments and FP-CIT [123I-N-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)] dopaminergic imaging. FP-CIT scans were blindly rated by a consensus panel and classified as normal or abnormal.
The sensitivity of visually rated FP-CIT imaging to detect combined possible or probable MCI-LB was 54.2% [95% confidence interval (CI) 39.2–68.6], with a specificity of 89.0% (95% CI 70.8–97.6) and a likelihood ratio for MCI-LB of 4.9, indicating that FP-CIT may be a clinically important test in MCI where any characteristic symptoms of Lewy body (LB) disease are present. The sensitivity in probable MCI-LB was 61.0% (95% CI 42.5–77.4) and in possible MCI-LB was 40.0% (95% CI 16.4–67.7).
Dopaminergic imaging had high specificity at the pre-dementia stage and gave a clinically important increase in diagnostic confidence and so should be considered in all patients with MCI who have any of the diagnostic symptoms of DLB. As expected, the sensitivity was lower in MCI-LB than in established DLB, although over 50% still had an abnormal scan. Accurate diagnosis of LB disease is important to enable early optimal treatment for LB symptoms.
The accurate clinical characterisation of mild cognitive impairment (MCI) is becoming increasingly important. The aim of this study was to compare the neuropsychiatric symptoms and cognitive profile of MCI with Lewy bodies (MCI-LB) with Alzheimer's disease MCI (MCI-AD).
Participants were ⩾60 years old with MCI. Each had a thorough clinical and neuropsychological assessment and 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane single photon emission computed tomography FP-CIT SPECT). MCI-LB was diagnosed if two or more diagnostic features of dementia with Lewy bodies were present (visual hallucinations, cognitive fluctuations, motor parkinsonism, rapid eye movement sleep behaviour disorder or positive FP-CIT SPECT). A Lewy body Neuropsychiatric Supportive Symptom Count (LBNSSC) was calculated based on the presence or absence of the supportive neuropsychiatric symptoms defined by the 2017 DLB diagnostic criteria: non-visual hallucinations, delusions, anxiety, depression and apathy.
MCI-LB (n = 41) had a higher LBNSSC than MCI-AD (n = 24; 1.8 ± 1.1 v. 0.7 ± 0.9, p = 0.001). 67% of MCI-LB had two or more of those symptoms, compared with 16% of MCI-AD (Likelihood ratio = 4.2, p < 0.001). MCI-LB subjects scored lower on tests of attention, visuospatial function and verbal fluency. However, cognitive test scores alone did not accurately differentiate MCI-LB from MCI-AD.
MCI-LB is associated with neuropsychiatric symptoms and a cognitive profile similar to established DLB. This supports the concept of identifying MCI-LB based on the presence of core diagnostic features of DLB and abnormal FP-CIT SPECT imaging. The presence of supportive neuropsychiatric clinical features identified in the 2017 DLB diagnostic criteria was helpful in differentiating between MCI-LB and MCI-AD.
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
We report the discovery in the Greenland ice sheet of a discrete layer of free nanodiamonds (NDs) in very high abundances, implying most likely either an unprecedented influx of extraterrestrial (ET) material or a cosmic impact event that occurred after the last glacial episode. From that layer, we extracted n-diamonds and hexagonal diamonds (lonsdaleite), an accepted ET impact indicator, at abundances of up to about 5×106 times background levels in adjacent younger and older ice. The NDs in the concentrated layer are rounded, suggesting they most likely formed during a cosmic impact through some process similar to carbon-vapor deposition or high-explosive detonation. This morphology has not been reported previously in cosmic material, but has been observed in terrestrial impact material. This is the first highly enriched, discrete layer of NDs observed in glacial ice anywhere, and its presence indicates that ice caps are important archives of ET events of varying magnitudes. Using a preliminary ice chronology based on oxygen isotopes and dust stratigraphy, the ND-rich layer appears to be coeval with ND abundance peaks reported at numerous North American sites in a sedimentary layer, the Younger Dryas boundary layer (YDB), dating to 12.9 ± 0.1 ka. However, more investigation is needed to confirm this association.
We have observed a period of rapid and intense optical-infrared brightness and polarization variability in the quasar 3C 279. The observations were obtained as part of an ongoing study of the optical-infrared continuum evolution in a sample of optically violent variable (OVV) quasars and BL Lacertae objects. Simultaneous broadband UBVRI photometric and polarimetric observations are used to study the optical continuum spectral evolution and wavelength dependent linear polarization and to search for broad near-ultraviolet continuum spectral components.