The mechanical response to hockey-specific running gait: implications for the objective monitoring of (p)rehabilitation.

Field hockey is characterized by a unique dribbling position which has been associated with a prevalence of low back pain and lumbar injury. To quantify the biomechanical response of the hockey-specific running gait, twelve field hockey players completed treadmill running at speeds of 6, 9 and 12 km·hr-1 with a normal running gait and whilst manipulating the hockey stick to replicate dribbling. Mechanical loading was quantified using tri-axial accelerometery at L4, and muscular activity was measured for biceps femoris (BF), gluteus medius (GM) and quadratus lumborum (QL) of each limb. Running with the stick elicited greater mechanical loading in the medio-lateral (p = 0.001) and antero-posterior (p = 0.003) planes, and increased peak (p = 0.004) and mean (p = 0.002) EMG response of QL (p = 0.004). The greater planar mechanical loading and QL activation in response to hockey-specific running technique support epidemiological observations of lower back pain prevalence. The sensitivity of uni-axial mechanical loading to the hockey-specific running posture provides an efficacious means of objectively monitoring mechanical loading in-vivo, whilst the QL activation response has implications for (p)rehabilitative interventions. Running posture and speed can be considered as discrete progressions when considering training load.

Early Last Interglacial ocean warming drove substantial ice mass loss from Antarctica.

The future response of the Antarctic ice sheet to rising temperatures remains highly uncertain. A useful period for assessing the sensitivity of Antarctica to warming is the Last Interglacial (LIG) (129 to 116 ky), which experienced warmer polar temperatures and higher global mean sea level (GMSL) (+6 to 9 m) relative to present day. LIG sea level cannot be fully explained by Greenland Ice Sheet melt (∼2 m), ocean thermal expansion, and melting mountain glaciers (∼1 m), suggesting substantial Antarctic mass loss was initiated by warming of Southern Ocean waters, resulting from a weakening Atlantic meridional overturning circulation in response to North Atlantic surface freshening. Here, we report a blue-ice record of ice sheet and environmental change from the Weddell Sea Embayment at the periphery of the marine-based West Antarctic Ice Sheet (WAIS), which is underlain by major methane hydrate reserves. Constrained by a widespread volcanic horizon and supported by ancient microbial DNA analyses, we provide evidence for substantial mass loss across the Weddell Sea Embayment during the LIG, most likely driven by ocean warming and associated with destabilization of subglacial hydrates. Ice sheet modeling supports this interpretation and suggests that millennial-scale warming of the Southern Ocean could have triggered a multimeter rise in global sea levels. Our data indicate that Antarctica is highly vulnerable to projected increases in ocean temperatures and may drive ice-climate feedbacks that further amplify warming.

Outcomes and prognostic factors for relapsed or refractory lymphoma patients in phase I clinical trials.

Background Although safety and prognostic factors for overall survival (OS) have been extensively studied in Phase I clinical trials on patients with solid tumours, data on lymphoma trials are scarce. Here, we investigated safety, outcomes and prognostic factors in relapsed or refractory lymphoma patients included in a series of Phase I trials. Method and patients All consecutive adult patients with recurrent/refractory lymphoma enrolled in 26 Phase I trials at a single cancer centre in France between January 2008 and June 2016 were retrospectively assessed. Results 133 patients (males: 65%) were included in the analysis. The median (range) age was 65 (23-86). Aggressive non-Hodgkin, indolent non-Hodgkin and Hodgkin types accounted for 64%, 25% and 11% of the patients, respectively. The patients had received a median (range) of 3 (1-13) lines of treatment prior to trial entry. The median [95% confidence interval] progression-free survival and OS times were 3.0 [1.8-3.6] and 17.8 [12.7-30.4] months, respectively. High-grade toxicity (grade 3 or higher, according to the National Cancer Institute's Common Terminology Criteria for Adverse Events classification) was experienced by 56 of the 133 patients (42%) and was related to the investigational drug in 44 of these cases (79%). No toxicity-related deaths occurred. Dose-limiting toxicity (DLT) was encountered in 11 (9%) of the 116 evaluable patients. High-grade toxicity occurred during the DLT period for 34 of the 56 patients (61%) and after the DLT period in the remaining 22 (39%). The main prognostic factors for poor OS were the histological type (i.e. tumour aggressiveness), an elevated serum LDH level, and a low serum albumin level. Early withdrawal from a trial was correlated with the performance status score, the histological type and the serum LDH level. The overall objective response and disease control rates were 24% and 57%, respectively. Conclusion Performance status, LDH, albumin and histological type (tumour aggressiveness) appear to be the most relevant prognostic factors for enrolling Phase I participants with relapsed or refractory lymphoma. 39% of the patients experienced a first high-grade toxic event after the dose-limiting toxicity period, suggesting that the conventional concept of dose-limiting toxicity (designed for chemotherapy) should be redefined in the era of modern cancer therapies.

Antibody drug conjugates in older patients: State of the art.

More than half of cancer cases occur in patients aged 65 years or older. The efficacy and safety of antibody drug conjugates (ADCs) in older patients remains an unclear subject as available evidence is limited. Geriatric population is underrepresented in clinical trials. Consequently, most of our knowledge regarding innovative therapeutics was studied on a younger population. In this review of published literature, we report the available information on efficacy, safety and pharmacokinetics of FDA approved ADCs for hematologic malignancies and solid tumors in the geriatric population. We explore the results of clinical trials dedicated for older individuals as well as subgroup analyses of the geriatric population in major trials evaluating these drugs. Available data suggest a similar efficacy in older adults as compared to general population. However, older patients might be prone to a higher rate of adverse events in incidence with a potential impact on quality of life. We lack data to support primary dose reductions or schedule modifications in this category of patients. No pharmacokinetic differences were reported between age groups. It is crucial to encourage the development of clinical trials dedicated to older patients with geriatric parameters (G8 score, G-CODE…) so that results can be more representative of this population outside of clinical trials.

The problem with picking: Permittance, escape and shame in problematic skin picking.

OBJECTIVES: Problematic skin picking (SP) is a poorly understood experience characterised by a drive to pick the skin and related psychosocial impact. In the DSM-5, problematic SP is classified as 'excoriation (skin picking) disorder'. The aim of this article is to present a rare qualitative perspective on the lived experience of problematic SP, prioritising participants' voices and sense-making. DESIGN: An in-depth qualitative study of individuals who self-identified as picking their skin problematically and experienced related distress. METHODS: Seventeen UK-based participants were recruited online and interviewed about their SP. Participants were given choice of interview modality, including instant messenger platforms, telephone, email and Skype, to maximise comfort and improve the accessibility of the study. Transcripts were analysed using thematic analysis. RESULTS: Three themes offering novel insight into the phenomenology of participants' SP are highlighted and explored: (1) how cognitions and circumstances drove and permitted SP, (2) how participants 'zoned out' while SP and the escape or relief that this attentional experience offered and (3) participants' feelings of shame and distress in how they felt their SP may appear to others. CONCLUSIONS: This study contributes in-depth and novel ideas to the understanding of SP phenomenology and identifies how environmental factors, cognitions, contextual distress and shame may be considerations in therapeutic intervention. It presents the complexity of SP sense-making and demonstrates the need for individual formulation.

The IBER study: a feasibility randomised controlled trial of imagery based emotion regulation for the treatment of anxiety in bipolar disorder.

BACKGROUND: Intrusive mental imagery is associated with anxiety and mood instability within bipolar disorder and therefore represents a novel treatment target. Imagery Based Emotion Regulation (IBER) is a brief structured psychological intervention developed to enable people to use the skills required to regulate the emotional impact of these images. METHODS: Participants aged 18 and over with a diagnosis of bipolar disorder and at least a mild level of anxiety were randomly assigned (1:1) to receive IBER plus treatment as usual (IBER + TAU) or treatment as usual alone (TAU). IBER was delivered in up to 12 sessions overs 16 weeks. Clinical and health economic data were collected at baseline, end of treatment and 16-weeks follow-up. Objectives were to inform the recruitment process, timeline and sample size estimate for a definitive trial and to refine trial procedures. We also explored the impact on participant outcomes of anxiety, depression, mania, and mood stability at 16-weeks and 32-weeks follow-up. RESULTS: Fifty-seven (28: IBER + TAU, 27: TAU) participants from two sites were randomised, with 50 being recruited within the first 12 months. Forty-seven (82%) participants provided outcome data at 16 and 32-weeks follow-up. Thirty-five participants engaged in daily mood monitoring at the 32-week follow-up stage. Retention in IBER treatment was high with 27 (96%) attending ≥ 7 sessions. No study participants experienced a serious adverse event. DISCUSSION: The feasibility criteria of recruitment, outcome completion, and intervention retention were broadly achieved, indicating that imagery-focused interventions for bipolar disorder are worthy of further investigation.

Pre-Therapeutic Sarcopenia among Cancer Patients: An Up-to-Date Meta-Analysis of Prevalence and Predictive Value during Cancer Treatment.

This study will address the prevalence of pre-therapeutic sarcopenia (PS) and its clinical impact during cancer treatment among adult cancer patients ≥ 18 years of age. A meta-analysis (MA) with random-effect models was performed via a MEDLINE systematic review, according to the PRISMA statement, focusing on articles published before February 2022 that reported observational studies and clinical trials on the prevalence of PS and the following outcomes: overall survival (OS), progression-free survival (PFS), post-operative complications (POC), toxicities (TOX), and nosocomial infections (NI). A total of 65,936 patients (mean age: 45.7-85 y) with various cancer sites and extensions and various treatment modes were included. Mainly defined by CT scan-based loss of muscle mass only, the pooled prevalence of PS was 38.0%. The pooled relative risks were 1.97, 1.76, 2.70, 1.47, and 1.76 for OS, PFS, POC, TOX, and NI, respectively (moderate-to-high heterogeneity, I2: 58-85%). Consensus-based algorithm definitions of sarcopenia, integrating low muscle mass and low levels of muscular strength and/or physical performance, lowered the prevalence (22%) and heterogeneity (I2 < 50%). They also increased the predictive values with RRs ranging from 2.31 (OS) to 3.52 (POC). PS among cancer patients is prevalent and strongly associated with poor outcomes during cancer treatment, especially when considering a consensus-based algorithm approach.

Patterning of the antero-ventral mammalian brain: Lessons from holoprosencephaly comparative biology in man and mouse.

Adult form and function are dependent upon the activity of specialized signaling centers that act early in development at the embryonic midline. These centers instruct the surrounding cells to adopt a positional fate and to form the patterned structures of the phylotypic embryo. Abnormalities in these processes have devastating consequences for the individual, as exemplified by holoprosencephaly in which anterior midline development fails, leading to structural defects of the brain and/or face. In the 25 years since the first association between human holoprosencephaly and the sonic hedgehog gene, a combination of human and animal genetic studies have enhanced our understanding of the genetic and embryonic causation of this congenital defect. Comparative biology has extended the holoprosencephaly network via the inclusion of gene mutations from multiple signaling pathways known to be required for anterior midline formation. It has also clarified aspects of holoprosencephaly causation, showing that it arises when a deleterious variant is present within a permissive genome, and that environmental factors, as well as embryonic stochasticity, influence the phenotypic outcome of the variant. More than two decades of research can now be distilled into a framework of embryonic and genetic causation. This framework means we are poised to move beyond our current understanding of variants in signaling pathway molecules. The challenges now at the forefront of holoprosencephaly research include deciphering how the mutation of genes involved in basic cell processes can also cause holoprosencephaly, determining the important constituents of the holoprosencephaly permissive genome, and identifying environmental compounds that promote holoprosencephaly. This article is categorized under: Congenital Diseases > Stem Cells and Development Congenital Diseases > Genetics/Genomics/Epigenetics Congenital Diseases > Molecular and Cellular Physiology Congenital Diseases > Environmental Factors.

Adapted Behavioural Activation for Bipolar Depression: A Randomised Multiple Baseline Case Series.

Behavioural Activation (BA) is associated with a substantial evidence base for treatment of acute unipolar depression, and has promise as an easily disseminable psychological intervention for bipolar depression. Using a randomised multiple baseline case series design we examined the feasibility and acceptability of an adapted version of BA in a U.K. outpatient sample of 12 adults with acute bipolar depression. Participants were allocated at random to a 3-8 week wait period before being offered up to 20 sessions of BA. They completed outcome measures at intake, pre- and post-treatment and weekly symptom measures across the study period. Retention in therapy was high (11/12 participants completed the target minimum number of sessions), and all participants returning acceptability measures reported high levels of satisfaction with the intervention. No therapy-related serious adverse events were reported, nor were there exacerbations in manic symptoms that were judged to be a result of the intervention. The pattern of change on outcome measures is consistent with the potential for clinical benefit; six of the nine participants with a stable baseline showed clinically significant improvement on the primary outcome measure. The findings suggest adapted BA for bipolar depression is a feasible and acceptable approach that merits further investigation.

Late Holocene climate anomaly concurrent with fire activity and ecosystem shifts in the eastern Australian Highlands.

The alpine area of the Australian mainland is highly sensitive to climate and environmental change, and potentially vulnerable to ecosystem tipping points. Over the next two decades the Australian alpine region is predicted to experience temperature increases of at least 1 °C, coupled with a substantial decrease in snow cover. Extending the short instrumental record in these regions is imperative to put future change into context, and potentially provide analogues of warming. We reconstructed past temperatures, using a lipid biomarker palaeothermometer technique and mercury flux changes for the past 3500 years from the sediments of Club Lake, a high-altitude alpine tarn in the Snowy Mountains, southeastern Australia. Using a multi-proxy framework, including pollen and charcoal analyses, high-resolution geochemistry, and ancient microbial community composition, supported by high-resolution 210Pb and AMS 14C dating, we investigated local and regional ecological and environmental changes occurring in response to changes in temperature. We find the region experienced a general warming trend over the last 3500 years, with a pronounced climate anomaly occurring between 1000 and 1600 cal yrs. BP. Shifts in vegetation took place during this warm period, characterised by a decline in alpine species and an increase in open woodland taxa which co-occurred with an increase in regional fire activity. Given the narrow altitudinal band of Australian alpine vegetation, any future warming has the potential to result in the extinction of alpine species, including several endemic to the area, as treelines are driven to higher elevations. These findings suggest ongoing conservation efforts will be needed to protect the vulnerable alpine environments from the combined threats of climate changes, fire and invasive species.

Health librarians: developing professional competence through a 'legitimate peripheral participation' model.

This feature considers the legitimate peripheral participation model in developing professional competencies in health librarianship. It is described how this model was used in the development of a framework for mapping and recognising the competencies gained by new health librarians at the Royal Free Hospital Medical Library. HS.

Comparison of inherited neural tube defects in companion animals and livestock.

Neural tube defects (NTDs) are congenital malformations resulting from the improper or incomplete closure of the neural tube during embryonic development. A number of similar malformations of the protective coverings surrounding the central nervous system are also often included under this umbrella term, which may not strictly fit this definition. A range of NTD phenotypes exist and have been reported in humans and a wide range of domestic and livestock species. In the veterinary literature, these include cases of anencephaly, encephalocele, dermoid sinus, spina bifida, and craniorachischisis. While environmental factors have a role, genetic predisposition may account for a significant part of the risk of NTDs in these animal cases. Studies of laboratory model species (fish, birds, amphibians, and rodents) have been instrumental in improving our understanding of the neurulation process. In mice, over 200 genes that may be involved in this process have been identified and variant phenotypes investigated. Like laboratory mouse models, domestic animals and livestock species display a wide range of NTD phenotypes. They remain, however, a largely underutilized population and could complement already established laboratory models. Here we review reports of NTDs in companion animals and livestock, and compare these to other animal species and human cases. We aim to highlight the potential of nonlaboratory animal models for mutation discovery as well as general insights into the mechanisms of neurulation and the development of NTDs.

Decadal-scale onset and termination of Antarctic ice-mass loss during the last deglaciation.

Emerging ice-sheet modeling suggests once initiated, retreat of the Antarctic Ice Sheet (AIS) can continue for centuries. Unfortunately, the short observational record cannot resolve the tipping points, rate of change, and timescale of responses. Iceberg-rafted debris data from Iceberg Alley identify eight retreat phases after the Last Glacial Maximum that each destabilized the AIS within a decade, contributing to global sea-level rise for centuries to a millennium, which subsequently re-stabilized equally rapidly. This dynamic response of the AIS is supported by (i) a West Antarctic blue ice record of ice-elevation drawdown >600 m during three such retreat events related to globally recognized deglacial meltwater pulses, (ii) step-wise retreat up to 400 km across the Ross Sea shelf, (iii) independent ice sheet modeling, and (iv) tipping point analysis. Our findings are consistent with a growing body of evidence suggesting the recent acceleration of AIS mass loss may mark the beginning of a prolonged period of ice sheet retreat and substantial global sea level rise.

The Pre-Operative GRADE Score Is Associated with 5-Year Survival among Older Patients with Cancer Undergoing Surgery.

We aimed to assess the prognostic value of the pre-operative GRADE score for long-term survival among older adults undergoing major surgery for digestive or non-breast gynaecological cancers. Between 2013 and 2019, 136 consecutive older adults with cancer were prospectively recruited from the PF-EC cohort study before major cancer surgery and underwent a geriatric assessment. The GRADE score includes weight loss, gait speed at the threshold of 0.8 m/s, cancer site and cancer extension. The primary outcome was post-operative 5-year mortality. Patients were classified as low risk (GRADE ≤ 8) or high risk (GRADE > 8) on the basis of the median score. A Cox multivariate proportional hazards regression model was performed to assess the association between pre-operative factors and 5-year mortality expressed by adjusted hazard ratio (aHR) and 95% CI. The median age was 80 years, 52% were men, 73% had colorectal cancer. The 30-day post-operative severe complication rate (Clavien-Dindo ≥ 3) was 37%. The 5-year post-operative mortality rate was 34.5%. A GRADE score ≥ 8 (aHR = 2.64 [1.34-5.21], p = 0.0002) was associated with post-operative mortality after adjustment for Body Mass Index < 21 kg/m2 and Instrumental Activities of Daily Living <3/4. By combining very simple geriatric and cancer parameters, the pre-operative GRADE score provides a discriminant prognosis and could help to choose the most suitable treatment strategy for older cancer patients, avoiding under or over-treatment.

Do Brief Mindfulness Interventions (BMI) and Health Enhancement Programs (HEP) Improve Sleep in Patients in Hemodialysis with Depression and Anxiety?

(1) Objective: to determine if a brief mindfulness intervention (BMI) and a health education program (HEP) could improve measures of insomnia in patients undergoing hemodialysis. (2) Methods: this was a planned secondary analysis of a randomized controlled trial of BMI vs. HEP for hemodialysis patients with depression and/or anxiety symptoms. The primary outcome for the analysis was the Athens Insomnia Scale (AIS). The secondary outcome was consolidation of daily inactivity (ConDI), an actigraphy measure that describes sleep continuity and is based on a sleep detection algorithm validated by polysomnography. We also explored whether changes in AIS and ConDI were associated with changes in depression, anxiety, and quality of life scores over 8-week follow-up. (3) Results: BMI and HEP groups did not differ significantly from one another. Exposure to BMI or HEP improved sleep quality (baseline AIS 9.9 (±5.0) vs. 8-week follow-up 6.4 (±3.9), (V = 155.5, p = 0.015)), but not ConDI. Improvements in AIS were associated with lower depression scores (Rho = 0.57, p = 0.01) and higher quality-of-life scores (Rho = 0.46, p = 0.04). (4) Conclusions: mindfulness and HEP may be helpful interventions to improve self-reported sleep quality in patients undergoing hemodialysis. Decreases in insomnia scores were associated with decreased depression symptoms and increased quality of life scores.

Brief Mindfulness Intervention vs. Health Enhancement Program for Patients Undergoing Dialysis: A Randomized Controlled Trial.

BACKGROUND: Between 20-50% of patients undergoing maintenance dialysis for end-stage kidney disease experience symptoms of depression and/or anxiety, associated with increased mortality, greater health care utilization, and decreased quality of life. It is unknown whether mindfulness-based interventions can improve depression and anxiety symptoms in patients receiving this treatment. METHODS: We conducted an 8-week multicenter randomized controlled trial comparing a brief mindfulness intervention (BMI) vs. an active control (Health Enhancement Program [HEP]) in 55 patients receiving dialysis with symptoms of depression and/or anxiety. The primary outcome was change in Patient Health Questionnaire-9 (PHQ-9) depression scores, with a primary analysis in participants with baseline PHQ-9 ≥ 10, and a secondary analysis including all participants. The secondary outcome was change in Generalized Anxiety Disorder-7 (GAD-7) anxiety scores with corresponding primary and secondary analyses. RESULTS: Both BMI and HEP reduced depressive symptoms, with no difference between trial arms (PHQ-9 change = -7.0 vs. -6.1, p = 0.62). BMI was more effective than HEP in reducing anxiety (GAD-7 change = -8.7 vs. -1.4, p = 0.01). Secondary analyses revealed no differences between arms. CONCLUSIONS: For patients undergoing dialysis, both BMI and HEP may be helpful interventions for depression symptoms, and BMI may be superior to HEP for anxiety symptoms. Mindfulness-based and other psychosocial interventions may be further evaluated in those undergoing dialysis as treatment options for symptoms of depression and anxiety.

Response to Comment on "A global environmental crisis 42,000 years ago".

Our study on the exact timing and the potential climatic, environmental, and evolutionary consequences of the Laschamps Geomagnetic Excursion has generated the hypothesis that geomagnetism represents an unrecognized driver in environmental and evolutionary change. It is important for this hypothesis to be tested with new data, and encouragingly, none of the studies presented by Picin et al. undermine our model.

Response to Comment on "A global environmental crisis 42,000 years ago".

Our paper about the impacts of the Laschamps Geomagnetic Excursion 42,000 years ago has provoked considerable scientific and public interest, particularly in the so-called Adams Event associated with the initial transition of the magnetic poles. Although we welcome the opportunity to discuss our new ideas, Hawks' assertions of misrepresentation are especially disappointing given his limited examination of the material.