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Reliable spatially resolved compositional analysis through atom probe tomography requires an accurate placement of the detected ions within the three-dimensional reconstruction. Unfortunately, for heterogeneous systems, traditional reconstruction protocols are prone to position some ions incorrectly. This stems from the use of simplified projection laws which treat the emitter apex as a spherical cap, although the actual shape may be far more complex. For instance, sampled materials with compositional heterogeneities are known to develop local variations in curvature across the emitter due to their material phase specific evaporation fields. This work provides three pivotal precursors to improve the spatial accuracy of the reconstructed volume in such cases. First, we show scanning probe microscopy enables the determination of the local curvature of heterogeneous emitters, thus providing the essential information for a more advanced reconstruction considering the actual shape. Second, we demonstrate the cyclability between scanning probe characterization and atom probe analysis. This is a key ingredient of more advanced reconstruction protocols whereby the characterization of the emitter topography is executed at multiple stages of the atom probe analysis. Third, we show advances in the development of an electrostatically driven reconstruction protocol which are expected to enable reconstruction based on experimental tip shapes.
Catatonia, a severe neuropsychiatric syndrome, has few studies of sufficient scale to clarify its epidemiology or pathophysiology. We aimed to characterise demographic associations, peripheral inflammatory markers and outcome of catatonia.
Electronic healthcare records were searched for validated clinical diagnoses of catatonia. In a case–control study, demographics and inflammatory markers were compared in psychiatric inpatients with and without catatonia. In a cohort study, the two groups were compared in terms of their duration of admission and mortality.
We identified 1456 patients with catatonia (of whom 25.1% had two or more episodes) and 24 956 psychiatric inpatients without catatonia. Incidence was 10.6 episodes of catatonia per 100 000 person-years. Patients with and without catatonia were similar in sex, younger and more likely to be of Black ethnicity. Serum iron was reduced in patients with catatonia [11.6 v. 14.2 μmol/L, odds ratio (OR) 0.65 (95% confidence interval (CI) 0.45–0.95), p = 0.03] and creatine kinase was raised [2545 v. 459 IU/L, OR 1.53 (95% CI 1.29–1.81), p < 0.001], but there was no difference in C-reactive protein or white cell count. N-Methyl-d-aspartate receptor antibodies were significantly associated with catatonia, but there were small numbers of positive results. Duration of hospitalisation was greater in the catatonia group (median: 43 v. 25 days), but there was no difference in mortality after adjustment.
In the largest clinical study of catatonia, we found catatonia occurred in approximately 1 per 10 000 person-years. Evidence for a proinflammatory state was mixed. Catatonia was associated with prolonged inpatient admission but not with increased mortality.
Land divisions are ubiquitous features of the British countryside. Field boundaries, enclosures, pit alignments, and other forms of land division have been used to shape and delineate the landscape over thousands of years. While these divisions are critical for understanding economies and subsistence, the organization of tenure and property, social structure and identity, and their histories of use have remained unclear. Here, the authors present the first robust, Bayesian statistical chronology for land division over three millennia within a study region in England. Their innovative approach to investigating long-term change demonstrates the unexpected scale of later ‘prehistoric’ land demarcation, which may correspond to the beginnings of increasing social hierarchy.
Rediscovery of living populations of a species that was presumed to be extirpated can generate new narratives for conservation in areas suffering from losses in biodiversity. We used field observations and DNA sequence data to verify the rediscovery of the Critically Endangered scincid lizard Emoia slevini on Dåno′, an islet off the coast of Guam in the southern Mariana Islands, where for > 20 years it had been considered possibly extirpated. Endemic to the Marianas, E. slevini has declined throughout its range and no longer occurs on as many as five islands from which it was historically known, most likely because of interactions with invasive species and loss of native forest. Our results show that individuals from Dåno′, the type locality for E. slevini, are genetically similar but not identical to E. slevini on Sarigan and Alamagan to the north, and that E. slevini is a close evolutionary relative to another congener in the southern Marianas that is currently recognized as Emoia atrocostata but probably represents an undescribed species in this archipelago. We also show that other, more broadly distributed species of Emoia occurring on Dåno′ are distant relatives to E. slevini and the Mariana lineage of E. atrocostata, providing further evidence of the distinctiveness of these taxa. The rediscovery of E. slevini on Dåno′ following rodent eradication and culling of a population of monitor lizards suggests that management of invasive species is key to the recovery of this skink in the Mariana Islands, and that a range eclipse on the larger neighbouring island of Guam best explains why the rediscovery took place at the periphery of the species’ historic range. A Chamorro abstract can be found in the supplementary material.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Functional benefits of the morphologies described by Bergmann's and Allen's rules in human males have recently been reported. However, the functional implications of ecogeographical patterning in females remain poorly understood. Here, we report the findings of preliminary work analysing the association between body shape and performance in female ultramarathon runners (n = 36) competing in hot and cold environments. The body shapes differed between finishers of hot and cold races, and also between hot race finishers and non-finishers. Variability in race performance across different settings supports the notion that human phenotype is adapted to different thermal environments as ecogeographical patterns have reported previously. This report provides support for the recent hypothesis that the heightened thermal strain associated with prolonged physical activity in hot/cold environments may have driven the emergence of thermally adaptive phenotypes in our evolutionary past. These results also tentatively suggest that the relationship between morphology and performance may be stronger in female vs. male athletes. This potential sex difference is discussed with reference to the evolved unique energetic context of human female reproduction. Further work, with a larger sample size, is required to investigate the observed potential sex differences in the strength of the relationship between phenotype and performance.
The ability to effectively lead an interdisciplinary translational team is a crucial component of team science success. Most KL2 Clinical Scholars have been members of scientific teams, but few have been team science leaders. There is a dearth of literature and outcome measures of effective Team Science Leadership in clinical and translational research. We focused our curriculum to emphasize Team Science Leadership, developed a list of Team Science Leadership competencies for translational investigators using a modified Delphi method, and incorporated the competencies into a quantitative evaluation survey. The survey is completed on entry and annually thereafter by the Scholar; the Scholar’s primary mentor and senior staff who educate and interact with the Scholar rate the Scholar at the end of each year. The program leaders and mentor review the results with each Scholar. The survey scales had high internal consistency and good factor structure. Overall ratings by mentors and senior staff were generally high, but ratings by Scholars tended to be lower, offering opportunities for discussion and career planning. Scholars rated the process favorably. A Team Science Leadership curriculum and periodic survey of attained competencies can inform individual career development and guide team science curriculum development.
Accurate diagnosis and appropriate treatment of tardive dyskinesia (TD) are imperative, as its symptoms can be highly disruptive to both patients and their caregivers. Misdiagnosis can lead to incorrect interventions with suboptimal or even deleterious results. To aid in the identification and differentiation of TD in the psychiatric practice setting, we review its clinical features and movement phenomenology, as well as those of other antipsychotic-induced movement disorders, with accompanying links to illustrative videos. Exposure to dopamine receptor blocking agents (DRBAs) such as antipsychotics or antiemetics is associated with a spectrum of movement disorders including TD. The differential diagnosis of TD is based on history of DRBA exposure, recent discontinuation or dose reduction of a DRBA, and movement phenomenology. Common diagnostic challenges are the abnormal behaviors and dyskinesias associated with advanced age or chronic mental illness, and other movement disorders associated with DRBA therapy, such as akathisia, parkinsonian tremor, and tremor related to use of mood stabilizing agents (eg, lithium, divalproex). Duration of exposure may help rule out acute drug-induced syndromes such as acute dystonia or acute/subacute akathisia. Another important consideration is the potential for TD to present together with other drug-induced movement disorders (eg, parkinsonism, parkinsonian tremor, and postural tremor from mood stabilizers) in the same patient, which can complicate both diagnosis and management. After documentation of the phenomenology, severity, and distribution of TD movements, treatment options should be reviewed with the patient and caregivers.
Forensic entomology is the use of arthropods as evidence in criminal or civil investigations. This field is well established within the forensic sciences with active practitioners and researchers located at many institutions throughout the world. In fact, a number of associations have been formed in recent years to serve as platforms for professional development in the field of forensic entomology.
The emphasis on team science in clinical and translational research increases the importance of collaborative biostatisticians (CBs) in healthcare. Adequate training and development of CBs ensure appropriate conduct of robust and meaningful research and, therefore, should be considered as a high-priority focus for biostatistics groups. Comprehensive training enhances clinical and translational research by facilitating more productive and efficient collaborations. While many graduate programs in Biostatistics and Epidemiology include training in research collaboration, it is often limited in scope and duration. Therefore, additional training is often required once a CB is hired into a full-time position. This article presents a comprehensive CB training strategy that can be adapted to any collaborative biostatistics group. This strategy follows a roadmap of the biostatistics collaboration process, which is also presented. A TIE approach (Teach the necessary skills, monitor the Implementation of these skills, and Evaluate the proficiency of these skills) was developed to support the adoption of key principles. The training strategy also incorporates a “train the trainer” approach to enable CBs who have successfully completed training to train new staff or faculty.