We formally introduce 14 new high-level stratigraphic names to augment existing names and to hierarchically organise all of New Zealand's onland and offshore Cambrian-Holocene rocks and ...unconsolidated deposits. The two highest-level units are Austral Superprovince (new) and Zealandia Megasequence (new). These encompass all stratigraphic units of the country's Cambrian-Early Cretaceous basement rocks and Late Cretaceous-Holocene cover rocks and sediments, respectively. Most high-level constituents of the Austral Superprovince are in current and common usage: Eastern and Western Provinces consist of 12 tectonostratigraphic terranes, 10 igneous suites, 5 batholiths and Haast Schist. Ferrar, Tarpaulin and Jaquiery suites (new) have been added to existing plutonic suites to describe all known compositional variation in the Tuhua Intrusives. Zealandia Megasequence consists of five predominantly sedimentary, partly unconformity-bounded units and one igneous unit. Momotu and Haerenga supergroups (new) comprise lowermost rift to passive margin (terrestrial to marine transgressive) rock units. Waka Supergroup (new) includes rocks related to maximum marine flooding linked to passive margin culmination in the east and onset of new tectonic subsidence in the west. Māui and Pākihi supergroups (new) comprise marine to terrestrial regressive rock and sediment units deposited during Neogene plate convergence. Rūaumoko Volcanic Region (new) is introduced to include all igneous rocks of the Zealandia Megasequence and contains the geochemically differentiated Whakaari, Horomaka and Te Raupua supersuites (new). Our new scheme, Litho2014, provides a complete, high-level stratigraphic classification for the continental crust of the New Zealand region.
Background Burnout is a complex syndrome of emotional distress that can disproportionately affect individuals who work in health care professions. Study Design For a national survey of burnout in US ...general surgery residents, we asked all ACGME-accredited general surgery program directors to email their general surgery residents an invitation to complete an anonymous, online survey. Burnout was assessed with the Maslach Burnout Inventory; total scores for Emotional Exhaustion (EE), Depersonalization (DP), and Personal Accomplishment (PA) subscales were calculated. Burnout was defined as having a score in the highest tertile for EE or DP or lowest tertile for PA. Chi-square tests and one-way ANOVA were used to test associations between burnout tertiles for each subscale and various resident and training-program characteristics as appropriate. Results From April to December 2014, six hundred and sixty-five residents actively engaged in clinical training had data for analysis; 69% met the criterion for burnout on at least one subscale. Higher burnout on each subscale was reported by residents planning private practice careers compared with academic careers. A greater proportion of women than men reported burnout on EE and PA. Higher burnout on EE and DP was associated with greater work hours per week. Having a structured mentoring program was associated with lower burnout on each subscale. Conclusions The high rates of burnout among general surgery residents are concerning, given the potential impact of burnout on the quality of patient care. Efforts to identify at-risk populations and to design targeted interventions to mitigate burnout in surgical trainees are warranted.
Plasma discharges with a negative triangularity (δ=-0.4) shape have been created in the DIII-D tokamak with a significant normalized beta (β_{N}=2.7) and confinement characteristic of the high ...confinement mode (H_{98y2}=1.2) despite the absence of an edge pressure pedestal and no edge localized modes (ELMs). These inner-wall-limited plasmas have a similar global performance as a positive triangularity (δ=+0.4) ELMing H-mode discharge with the same plasma current, elongation and cross sectional area. For cases both of dominant electron cyclotron heating with T_{e}/T_{i}>1 and dominant neutral beam injection heating with T_{e}/T_{i}=1, turbulent fluctuations over radii 0.5<ρ<0.9 were reduced by 10-50% in the negative triangularity shape compared to the matching positive triangularity shape, depending on the radius and conditions.
Mitochondrial diseases are clinically heterogeneous disorders caused by a wide spectrum of mutations in genes encoded by either the nuclear or the mitochondrial genome. Treatments for mitochondrial ...diseases are currently focused on symptomatic management rather than improving the biochemical defect caused by a particular mutation. This review focuses on the latest advances in the development of treatments for mitochondrial disease, both small molecules and gene therapies, as well as methods to prevent transmission of mitochondrial disease through the germline.
Russell et al. review recent progress in the varied approaches to treat and prevent mitochondrial disease, including small-molecule-based approaches to improve mitochondrial function or turnover, manipulation of the mitochondrial genome, and mitochondrial replacement therapy.
Abstract Objectives To evaluate the epidemiology of, and post-intensive care unit (ICU) interventions for anxiety symptoms after critical illness. Methods We searched 5 databases (1970–2015) to ...identify studies assessing anxiety symptoms in adult ICU survivors. Data from studies using the most common assessment instrument were meta-analyzed. Results We identified 27 studies (2880 patients) among 27,334 citations. The Hospital Anxiety and Depression Scale-Anxiety subscale (HADS-A) was the most common instrument (81% of studies). We pooled data at 2–3, 6, and 12–14 month time-points, with anxiety symptom prevalences (HADS-A≥8, 95%CI) of 32%(27–38%), 40%(33–46%), and 34%(25–42%), respectively. In a subset of studies with repeated assessments in the exact same patients, there was no significant change in anxiety score or prevalence over time. Age, gender, severity of illness, diagnosis, and length of stay were not associated with anxiety symptoms. Psychiatric symptoms during admission and memories of in-ICU delusional experiences were potential risk factors. Physical rehabilitation and ICU diaries had potential benefit. Conclusions One-third of ICU survivors experience anxiety symptoms that are persistent during their first year of recovery. Psychiatric symptoms during admission and memories of in–ICU delusional experiences were associated with post-ICU anxiety. Physical rehabilitation and ICU diaries merit further investigation as possible interventions.
Abstract
The discovery of two-dimensional magnets has initiated a new field of research, exploring both fundamental low-dimensional magnetism, and prospective spintronic applications. Recently, ...observations of magnetic skyrmions in the 2D ferromagnet Fe
3
GeTe
2
(FGT) have been reported, introducing further application possibilities. However, controlling the exhibited magnetic state requires systematic knowledge of the history-dependence of the spin textures, which remains largely unexplored in 2D magnets. In this work, we utilise real-space imaging, and complementary simulations, to determine and explain the thickness-dependent magnetic phase diagrams of an exfoliated FGT flake, revealing a complex, history-dependent emergence of the uniformly magnetised, stripe domain and skyrmion states. The results show that the interplay of the dominant dipolar interaction and strongly temperature dependent out-of-plane anisotropy energy terms enables the selective stabilisation of all three states at zero field, and at a single temperature, while the Dzyaloshinksii-Moriya interaction must be present to realise the observed Néel-type domain walls. The findings open perspectives for 2D devices incorporating topological spin textures.
Additional neurological features have recently been described in seven families transmitting pathogenic mutations in OPA1, the most common cause of autosomal dominant optic atrophy. However, the ...frequency of these syndromal ‘dominant optic atrophy plus’ variants and the extent of neurological involvement have not been established. In this large multi-centre study of 104 patients from 45 independent families, including 60 new cases, we show that extra-ocular neurological complications are common in OPA1 disease, and affect up to 20% of all mutational carriers. Bilateral sensorineural deafness beginning in late childhood and early adulthood was a prominent manifestation, followed by a combination of ataxia, myopathy, peripheral neuropathy and progressive external ophthalmoplegia from the third decade of life onwards. We also identified novel clinical presentations with spastic paraparesis mimicking hereditary spastic paraplegia, and a multiple sclerosis-like illness. In contrast to initial reports, multi-system neurological disease was associated with all mutational subtypes, although there was an increased risk with missense mutations odds ratio = 3.06, 95% confidence interval = 1.44–6.49; P = 0.0027, and mutations located within the guanosine triphosphate-ase region (odds ratio = 2.29, 95% confidence interval = 1.08–4.82; P = 0.0271). Histochemical and molecular characterization of skeletal muscle biopsies revealed the presence of cytochrome c oxidase-deficient fibres and multiple mitochondrial DNA deletions in the majority of patients harbouring OPA1 mutations, even in those with isolated optic nerve involvement. However, the cytochrome c oxidase-deficient load was over four times higher in the dominant optic atrophy + group compared to the pure optic neuropathy group, implicating a causal role for these secondary mitochondrial DNA defects in disease pathophysiology. Individuals with dominant optic atrophy plus phenotypes also had significantly worse visual outcomes, and careful surveillance is therefore mandatory to optimize the detection and management of neurological disability in a group of patients who already have significant visual impairment.
Research evaluating acute respiratory failure (ARF) survivors' outcomes after hospital discharge has substantial heterogeneity in terms of the measurement instruments used, creating barriers to ...synthesizing study data.
To identify a minimum set of core outcome measures that are essential to include in all clinical research studies evaluating ARF survivors after discharge.
We conducted a three-round modified Delphi consensus process with 77 participants (47% female, 55% outside the United States), including clinical researchers from more than 16 countries across six continents, patients/caregivers, clinicians, and research funders. Participants reviewed standardized information on measure instruments for seven consensus-derived outcomes plus one recommended outcome.
Response rates were 91 to 97% across the three rounds. Among 75 measurement instruments evaluated, the following met a priori consensus criteria: EQ-5D and 36-item Short Form Health Survey version 2 (optional) for the "satisfaction with life and personal enjoyment" and "pain" outcomes, and both the Hospital Anxiety and Depression Scale and the Impact of Events Scale-Revised for the "mental health" outcome. No measures reached consensus for the following outcomes: cognition, muscle and/or nerve function, physical function, and pulmonary function. All measures considered for pulmonary function met consensus criteria for exclusion. The following measures did not reach the threshold for consensus but achieved the highest scores for their respective outcomes: the Montreal Cognitive Assessment (cognition), manual muscle testing and handgrip dynamometry (muscle and/or nerve function), and 6-minute-walk test (physical function).
This Core Outcome Measurement Set is recommended for use in all clinical research evaluating ARF survivors after hospital discharge. In the future, researchers should evaluate measures for outcomes not reaching consensus.
Although denervation has long been implicated in aging muscle, the degree to which it is causes the fiber atrophy seen in aging muscle is unknown. To address this question, we quantified motoneuron ...soma counts in the lumbar spinal cord using choline acetyl transferase immunhistochemistry and quantified the size of denervated versus innervated muscle fibers in the gastrocnemius muscle using the in situ expression of the denervation-specific sodium channel, Nav₁.₅, in young adult (YA) and senescent (SEN) rats. To gain insights into the mechanisms driving myofiber atrophy, we also examined the myofiber expression of the two primary ubiquitin ligases necessary for muscle atrophy (MAFbx, MuRF1). MN soma number in lumbar spinal cord declined 27% between YA (638±34 MNs×mm⁻¹) and SEN (469±13 MNs×mm⁻¹). Nav₁.₅ positive fibers (1548±70 μm²) were 35% smaller than Nav₁.₅ negative fibers (2367±78 μm²; P<0.05) in SEN muscle, whereas Nav₁.₅ negative fibers in SEN were only 7% smaller than fibers in YA (2553±33 μm²; P<0.05) where no Nav₁.₅ labeling was seen, suggesting denervation is the primary cause of aging myofiber atrophy. Nav₁.₅ positive fibers had higher levels of MAFbx and MuRF1 (P<0.05), consistent with involvement of the proteasome proteolytic pathway in the atrophy of denervated muscle fibers in aging muscle. In summary, our study provides the first quantitative assessment of the contribution of denervation to myofiber atrophy in aging muscle, suggesting it explains the majority of the atrophy we observed. This striking result suggests a renewed focus should be placed on denervation in seeking understanding of the causes of and treatments for aging muscle atrophy.
Cancer diagnostics and surgery have been disrupted by the response of health care services to the coronavirus disease 2019 (COVID-19) pandemic. Progression of cancers during delay will impact on ...patients' long-term survival.
We generated per-day hazard ratios of cancer progression from observational studies and applied these to age-specific, stage-specific cancer survival for England 2013–2017. We modelled per-patient delay of 3 and 6 months and periods of disruption of 1 and 2 years. Using health care resource costing, we contextualise attributable lives saved and life-years gained (LYGs) from cancer surgery to equivalent volumes of COVID-19 hospitalisations.
Per year, 94 912 resections for major cancers result in 80 406 long-term survivors and 1 717 051 LYGs. Per-patient delay of 3/6 months would cause attributable death of 4755/10 760 of these individuals with loss of 92 214/208 275 life-years, respectively. For cancer surgery, average LYGs per patient are 18.1 under standard conditions and 17.1/15.9 with a delay of 3/6 months (an average loss of 0.97/2.19 LYGs per patient), respectively. Taking into account health care resource units (HCRUs), surgery results on average per patient in 2.25 resource-adjusted life-years gained (RALYGs) under standard conditions and 2.12/1.97 RALYGs following delay of 3/6 months. For 94 912 hospital COVID-19 admissions, there are 482 022 LYGs requiring 1 052 949 HCRUs. Hospitalisation of community-acquired COVID-19 patients yields on average per patient 5.08 LYG and 0.46 RALYGs.
Modest delays in surgery for cancer incur significant impact on survival. Delay of 3/6 months in surgery for incident cancers would mitigate 19%/43% of LYGs, respectively, by hospitalisation of an equivalent volume of admissions for community-acquired COVID-19. This rises to 26%/59%, respectively, when considering RALYGs. To avoid a downstream public health crisis of avoidable cancer deaths, cancer diagnostic and surgical pathways must be maintained at normal throughput, with rapid attention to any backlog already accrued.
•Lockdown and re-deployment due to the COVID-19 pandemic have caused significant disruption to cancer diagnosis and management.•A 3-month delay to surgery across all stage 1–3 cancers is estimated to cause >4700 attributable deaths per year in England.•The impact on life-years lost of 3–6-month delay to surgery for stage 1–3 disease varies widely between tumour types.•Strategic prioritisation of patients for diagnostics and surgery has potential to mitigate deaths attributable to delays.•The resource-adjusted benefit in avoiding delay in cancer management compares favourably with admission for COVID-19 infection.
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