bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aligning intuition and theory: enhancing the replicability of behaviour change interventions in cancer genetics
Authors: Taylor Natalie , Healey Emma , Morrow April , Greening Sian , Wakefield Claire E. , Warwick Linda , Williams Rachel , Tucker Katherine M. 
Published: October 2020

AbstractBackgroundDespite considerable encouragement for healthcare professionals to use or be clear about the theory used in their improvement programmes, the uptake of these approaches to design interventions or report their content is lacking. Recommendations suggest healthcare practitioners work with social and/or behavioural scientists to gain expertise in programme theory, ideally before, but even during or after the work is done. We aim to demonstrate the extent to which intuitive intervention strategies designed by healthcare professionals to overcome patient barriers to communicating genetic cancer risk information to family members align with a theoretical framework of behaviour change.MethodsAs part of a pre-post intervention study, a team of genetic counsellors aimed to understand, and design interventions to overcome, the major barriers a group of familial cancer patients face around communicating hereditary cancer risk information to their relatives. A behavioural change specialist worked with the team to review and recode barriers and interventions according to the Theoretical Domains Framework (TDF) and 93 behaviour change techniques (BCTs). Resulting BCTs were cross-referenced against the Theory and Techniques Tool to examine whether evidence-based mechanistic links have been established to date.ResultsFive themes emerged from the genetic counsellor coded barriers, which when recoded according to the TDF represented seven domains of behaviour change. Forty-five experiential and intuitive interventions were used to tackle key barriers. These were represented by 21 BCTs, which were found to be used on 131 occasions. The full mapping exercise is presented, resulting in a suite of intervention strategies explicitly linked to a theoretical framework. Structured, written reflections were provided retrospectively by the core clinical team.ConclusionsAlthough the ideal is to use theory prospectively, or even whilst a project is underway, making links between theory and interventions explicit, even retrospectively, can contribute towards standardising intervention strategies, furthering understanding of intervention effects, and enhancing the opportunities for accurate replicability and generalisability across other settings. Demonstrating to healthcare professionals how their intuition aligns with theory may highlight the additional benefits that theory has to offer and serve to promote its use in improvement.
Deep learning a poroelastic rock-physics model for pressure and saturation discrimination
Authors: Weinzierl Wolfgang , Wiese Bernd 
Published: October 2020

Determining saturation and pore pressure is relevant for hydrocarbon production as well as natural gas and [Formula: see text] storage. In this context, seismic methods provide spatially distributed data used to determine gas and fluid migration. A method is developed that allows the determination of saturation and reservoir pressure from seismic data, more accurately from the rock-physics attributes of velocity, attenuation, and density. Two rock-physics models based on Hertz-Mindlin-Gassmann and Biot-Gassmann are developed. Both generate poroelastic attributes from pore pressure, gas saturation, and other rock-physics parameters. The rock-physics models are inverted with deep neural networks to derive saturation, pore pressure, and porosity from rock-physics attributes. The method is demonstrated with a 65 m deep unconsolidated high-porosity reservoir at the Svelvik ridge, Norway. Tests for the most suitable structure of the neural network are carried out. Saturation and pressure can be meaningfully determined under the condition of a gas-free baseline with known pressure and data from an accurate seismic campaign, preferably cross-well seismic. Including seismic attenuation increases the accuracy. Although training requires hours, predictions can be made in only a few seconds, allowing for rapid interpretation of seismic results.
First-in-Human Phase I Study of Iadademstat (ORY-1001): A First-in-Class Lysine-Specific Histone Demethylase 1A Inhibitor, in Relapsed or Refractory Acute Myeloid Leukemia
Authors: Salamero Olga , Montesinos Pau , Willekens Christophe , Pérez-Simón José Antonio , Pigneux Arnaud , Récher Christian , Popat Rakesh , Carpio Cecilia , Molinero César , Mascaró Cristina , Vila Joaquim , Arévalo M. Isabel , Maes Tamara , Buesa Carlos , Bosch Francesc , Somervaille Tim C. P. 
Published: October 2020

PURPOSE Iadademstat is a novel, highly potent, and selective inhibitor of LSD1 (KDM1A), with preclinical in vitro and in vivo antileukemic activity. This study aimed to determine safety and tolerability of iadademstat as monotherapy in patients with relapsed/refractory acute myeloid leukemia (R/R AML). METHODS This phase I, nonrandomized, open-label, dose-escalation (DE), and extension-cohort (EC) trial included patients with R/R AML and evaluated the safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antileukemic activity of this orally bioavailable first-in-class lysine-specific demethylase 1 inhibitor. RESULTS Twenty-seven patients were treated with iadademstat on days 1 to 5 (5-220 µg/m2/d) of each week in 28-day cycles in a DE phase that resulted in a recommended dose of 140 µg/m2/d of iadademstat as a single agent. This dose was chosen to treat all patients (n = 14) in an EC enriched with patients with MLL/KMT2A-rearranged AML. Most adverse events (AEs) were as expected in R/R AML and included myelosuppression and nonhematologic AEs, such as infections, asthenia, mucositis, and diarrhea. PK data demonstrated a dose-dependent increase in plasma exposure, and PD data confirmed a potent time- and exposure-dependent induction of differentiation biomarkers. Reductions in blood and bone marrow blast percentages were observed, together with induction of blast cell differentiation, in particular, in patients with MLL translocations. One complete remission with incomplete count recovery was observed in the DE arm. CONCLUSION Iadademstat exhibits a good safety profile together with signs of clinical and biologic activity as a single agent in patients with R/R AML. A phase II trial of iadademstat in combination with azacitidine is ongoing (EudraCT No.: 2018-000482-36).
Dietary Fiber, Genetic Variations of Gut Microbiota-derived Short-chain Fatty Acids, and Bone Health in UK Biobank
Authors: Zhou Tao , Wang Mengying , Ma Hao , Li Xiang , Heianza Yoriko , Qi Lu 
Published: October 2020

Abstract

Context
Dietary fiber intake may relate to bone health.

Objective
To investigate whether dietary fiber intake is associated with bone mineral density (BMD), and the modification effect of genetic variations related to gut microbiota-derived short-chain fatty acids (SCFAs).

Design
The associations of dietary fiber intake with estimated BMD derived from heel ultrasound and fractures were assessed in 224 630 and 384 134 participants from the UK Biobank.

Setting
UK Biobank.

Main Outcome Measures
Estimated BMD derived from heel ultrasound

Results
Higher dietary fiber intake (per standard deviation) was significantly associated with higher heel-BMD (β [standard error] = 0.0047 [0.0003], P = 1.10 × 10–54). Similarly significant associations were observed for all the fiber subtypes including cereal, fruit (dried and raw), and vegetable (cooked and raw) (all P &lt; .05). A positive association was found in both women and men but more marked among men except for dietary fiber in cooked vegetables (all Pinteraction &lt; .05). A protective association was found between dietary fiber intake and hip fracture (hazard ratio, 95% confidence interval: 0.94, 0.89-0.99; P = 3.0 × 10–2). In addition, the association between dietary fiber and heel BMD was modified by genetically determined SCFA propionate production (Pinteraction = 5.1 × 10–3). The protective association between dietary fiber and heel BMD was more pronounced among participants with lower genetically determined propionate production.

Conclusions
Our results indicate that greater intakes of total dietary fiber and subtypes from various food sources are associated with higher heel-BMD. Participants with lower genetically determined propionate production may benefit more from taking more dietary fiber.
Sleep, Sedentary Behavior, Physical Activity, and Cardiovascular Health: MESA
Authors: GERMAN CHARLES , MAKAREM NOUR , FANNING JASON , REDLINE SUSAN , ELFASSY TALI , MCCLAIN AMANDA , ABDALLA MARWAH , AGGARWAL BROOKE , ALLEN NORRINA , CARNETHON MERCEDES 
Published: October 2020

ABSTRACT

Introduction
Sleep, sedentary behavior, and physical activity are each independently associated with cardiovascular health (CVH). It is unknown how substituting time in sedentary behavior with sleep or physical activity affects overall CVH.

Methods
Data for this analysis were taken from the Multi-Ethnic Study on Atherosclerosis Sleep Ancillary Study. Eligible participants (N = 1718) wore Actiwatch accelerometers for 24 h and had at least 3 d of valid accelerometry. The American Heart Association’s Life’s Simple 7 was used to represent the CVH score after excluding the physical activity component, with higher scores indicating more favorable CVH. Isotemporal substitution modeling was conducted to examine the effect of substituting 30 min of sedentary time for an equivalent amount of sleep, light-intensity physical activity (LIPA), or moderate to vigorous physical activity (MVPA).

Results
Substituting 30 min of sedentary time to sleep, LIPA, and MVPA was associated with a significantly higher CVH score [β (95% confidence interval) = 0.077 (0.056), 0.039 (0.033), and 0.485 (0.127), respectively]. Substituting 30 min of sedentary time to sleep was associated with lower body mass index (BMI). Substituting 30 min of sedentary time to LIPA was associated with higher diastolic blood pressure and total cholesterol, and lower BMI. Substituting 30 min of sedentary time to MVPA was associated with lower systolic and diastolic blood pressure, and lower BMI.

Conclusions
Sleep, LIPA, and MVPA are all associated with more favorable overall CVH and several key risk factors for cardiovascular disease. These findings underscore the importance of lifestyle modifications in improving CVH.
Carbohydrate Supplementation and the Influence of Breakfast on Fuel Use in Hypoxia
Authors: GRIFFITHS ALEX , DEIGHTON KEVIN , BOOS CHRISTOPHER J. , ROWE JOSHUA , MORRISON DOUGLAS J. , PRESTON TOM , KING RODERICK , O’HARA JOHN P. 
Published: October 2020

ABSTRACT

Purpose
This study investigated the effect of carbohydrate supplementation on substrate oxidation during exercise in hypoxia after preexercise breakfast consumption and omission.

Methods
Eleven men walked in normobaric hypoxia (FiO2 ~11.7%) for 90 min at 50% of hypoxic V˙O2max. Participants were supplemented with a carbohydrate beverage (1.2 g·min−1 glucose) and a placebo beverage (both enriched with U-13C6 D-glucose) after breakfast consumption and after omission. Indirect calorimetry and isotope ratio mass spectrometry were used to calculate carbohydrate (exogenous and endogenous [muscle and liver]) and fat oxidation.

Results
In the first 60 min of exercise, there was no significant change in relative substrate oxidation in the carbohydrate compared with placebo trial after breakfast consumption or omission (both P = 0.99). In the last 30 min of exercise, increased relative carbohydrate oxidation occurred in the carbohydrate compared with placebo trial after breakfast omission (44.0 ± 8.8 vs 28.0 ± 12.3, P < 0.01) but not consumption (51.7 ± 12.3 vs 44.2 ± 10.4, P = 0.38). In the same period, a reduction in relative liver (but not muscle) glucose oxidation was observed in the carbohydrate compared with placebo trials after breakfast consumption (liver, 7.7% ± 1.6% vs 14.8% ± 2.3%, P < 0.01; muscle, 25.4% ± 9.4% vs 29.4% ± 11.1%, P = 0.99) and omission (liver, 3.8% ± 0.8% vs 8.7% ± 2.8%, P < 0.01; muscle, 19.4% ± 7.5% vs 19.2% ± 12.2%, P = 0.99). No significant difference in relative exogenous carbohydrate oxidation was observed between breakfast consumption and omission trials (P = 0.14).

Conclusion
In acute normobaric hypoxia, carbohydrate supplementation increased relative carbohydrate oxidation during exercise (>60 min) after breakfast omission, but not consumption.
Increased Duration of Exercise Decreases Rate of Nonresponse to Exercise but May Not Decrease Risk for Cancer Mortality
Authors: LIN DAN , POTIAUMPAI MELANIE , SCHMITZ KATHRYN , STURGEON KATHLEEN 
Published: October 2020

ABSTRACT

Introduction
Previous studies have observed an inverse relationship between exercise and breast cancer risk. However, there is interindividual variability in response to exercise training interventions. We investigated whether increasing the dose of aerobic exercise (150 or 300 min·wk−1), while keeping intensity of exercise constant (70%–80% HRmax), decreases the number of exercise nonresponders and further decreases associated risk for cancer mortality in our study population of women genetically predisposed for breast cancer.

Methods
Healthy premenopausal women at elevated risk of breast cancer were randomized into control (<75 min·wk−1, n = 47), low-dose exercise (150 min·wk−1, n = 39), and high-dose exercise groups (300 min·wk−1, n = 39) for approximately 6 months. We assessed 1) clinical effectiveness (CE), defined as an improvement in predicted V˙O2max of ≥1 mL·kg−1·min−1, and twice the typical error (2× TE) of V˙O2max as thresholds to classify exercise “nonresponders”; 2) CE and 2× TE relative to exercise adherence levels; and 3) related changes in V˙O2max to predicted cancer mortality risk.

Results
After our 6-month intervention, we observed that 23.5% of women in the low-dose group and 5.6% of women in the high-dose group were clinical nonresponders (P = 0.04). Clinical nonresponder status was independent of adherence level. Associated reduction in risk for cancer mortality was observed among 87.2% of women in the low-dose group and 94.9% in the high-dose group (P = 0.43).

Conclusion
Increasing volume (not intensity) of exercise via time spent exercising significantly decreases the number of “nonresponders.” True nonresponders were observed as some women did not improve their fitness capacity despite high exercise adherence levels. Lastly, it appears 150 min·wk−1 is sufficient to decrease the predicted risk of cancer mortality.
Current provision of simulation in the UK and Republic of Ireland trauma and orthopaedic specialist training: a national survey
Authors: James Hannah K. , Gregory Robert J. H. , Tennent Duncan , Pattison Giles T. R. , Fisher Joanne D. , Griffin Damian R. 
Published: October 2020

Aims The primary aim of the survey was to map the current provision of simulation training within UK and Republic of Ireland (RoI) trauma and orthopaedic (T&O) specialist training programmes to inform future design of a simulation based-curriculum. The secondary aims were to characterize; the types of simulation offered to trainees by stage of training, the sources of funding for simulation, the barriers to providing simulation in training, and to measure current research activity assessing the educational impact of simulation. Methods The development of the survey was a collaborative effort between the authors and the British Orthopaedic Association Simulation Group. The survey items were embedded in the Performance and Opportunity Dashboard, which annually audits quality in training across several domains on behalf of the Speciality Advisory Committee (SAC). The survey was sent via email to the 30 training programme directors in March 2019. Data were retrieved and analyzed at the Warwick Clinical Trials Unit, UK. Results Overall, 28 of 30 programme directors completed the survey (93%). 82% of programmes had access to high-fidelity simulation facilities such as cadaveric laboratories. More than half (54%) had access to a non-technical skills simulation training. Less than half (43%) received centralized funding for simulation, a third relied on local funding such as the departmental budget, and there was a heavy reliance on industry sponsorship to partly or wholly fund simulation training (64%). Provision was higher in the mid-stages (ST3-5) compared to late-stages (ST6-8) of training, and was formally timetabled in 68% of prostgrammes. There was no assessment of the impact of simulation training using objective behavioural measures or real-world clinical outcomes. Conclusion There is currently widespread, but variable, provision of simulation in T&O training in the UK and RoI, which is likely to expand further with the new curriculum. It is important that research activity into the impact of simulation training continues, to develop an evidence base to support investment in facilities and provision.
The treatment of coccydynia in adolescents
Authors: Kalstad Ante Matti , Knobloch Rainer Günter , Finsen Vilhjalmur 
Published: October 2020

Aims To determine if the results of treatment of adolescents with coccydynia are similar to those found in adults. Adult patients with coccydynia may benefit from injection therapy or operative treatment. There is little data evaluating treatment results in adolescents. We have treated adolescent patients similarly to adults and compared the outcomes. Methods Overall, 32 adolescents with coccydynia were treated at our institution during a seven-year period; 28 responded to final follow-up questionnaires after a minimum of one year, 14 had been treated with only injection therapy, and 14 had been operated with coccygectomy. We collected data with regards to pain while sitting, leaning forward, rising from a sitting position, during defecation, while walking or jogging, and while travelling in trains, planes, or automobiles. Pain at follow-up was registered on a numeric pain scale. Each adolescent was then matched to adult patients, and results compared in a case control fashion. The treatment was considered successful if respondents were either completely well or much better at final follow-up after one to seven years. Results Out of the 28 treated adolescents, 14 were regarded as successfully treated. Seven were somewhat better, and the remaining seven were unchanged. In the adult control group the corresponding number was 15 successfully treated, eight patients were somewhat better, and five were unchanged. Six of the 14 successfully treated adolescents had been operated. There were no significant differences between the groups in the various registered domains, or on numeric pain scale. Conclusion Treatment results in adolescent patients seem similar to those in adults. The long-term success rate of injection therapy is low. In case of injection treatment failure, operation may be considered, also in adolescents.
COVID-19 and orthopaedic surgery: evolving strategies and early experience
Authors: Mathai Naveen J. , Venkatesan Aakaash Sethuraman , Key Thomas , Wilson Christopher , Mohanty Khitish 
Published: October 2020

Aims COVID-19 has changed the practice of orthopaedics across the globe. The medical workforce has dealt with this outbreak with varying strategies and adaptations, which are relevant to its field and to the region. As one of the ‘hotspots’ in the UK , the surgical branch of trauma and orthopaedics need strategies to adapt to the ever-changing landscape of COVID-19. Methods Adapting to the crisis locally involved five operational elements: 1) triaging and workflow of orthopaedic patients; 2) operation theatre feasibility and functioning; 3) conservation of human resources and management of workforce in the department; 4) speciality training and progression; and 5) developing an exit strategy to resume elective work. Two hospitals under our trust were redesignated based on the treatment of COVID-19 patients. Registrar/consultant led telehealth reviews were carried out for early postoperative patients. Workflows for the management of outpatient care and inpatient care were created. We looked into the development of a dedicated operating space to perform the emergency orthopaedic surgeries without symptoms of COVID-19. Between March 23 and April 23, 2020, we have surgically treated 133 patients across both our hospitals in our trust. This mainly included hip fractures and fractures/infection affecting the hand. Conclusion The COVID-19 pandemic is not the first disease outbreak affecting the UK, nor will it be the last. The current crisis has necessitated rapid development of new hospital guidelines and early adaptive strategies in our services. Protocols and directives need to be formalized keeping in mind that COVID-19 will have a long and protracted course until a definitive cure is discovered.
Subtrochanteric femoral shortening for hip centre restoration in complex total hip arthroplasty with functional outcome
Authors: Oommen A. T. , Chandy V. J. , Jeyaraj Christo , Kandagaddala Madhavi , Hariharan T. D. , Arun Shankar A. , Poonnoose P. M. , Korula Ravi Jacob 
Published: October 2020

Aims Complex total hip arthroplasty (THA) with subtrochanteric shortening osteotomy is necessary in conditions other than developmental dysplasia of the hip (DDH) and septic arthritis sequelae with significant proximal femur migration. Our aim was to evaluate the hip centre restoration with THAs in these hips. Methods In all, 27 THAs in 25 patients requiring THA with femoral shortening between 2012 and 2019 were assessed. Bilateral shortening was required in two patients. Subtrochanteric shortening was required in 14 out of 27 hips (51.9%) with aetiology other than DDH or septic arthritis. Vertical centre of rotation (VCOR), horizontal centre of rotation, offset, and functional outcome was calculated. The mean followup was 24.4 months (5 to 92 months). Results The mean VCOR was 17.43 mm (9.5 to 27 mm) and horizontal centre of rotation (HCOR) was 24.79 mm (17.2 to 37.6 mm). Dislocation at three months following acetabulum reconstruction required femoral shortening for offset correction and hip centre restoration in one hip. Mean horizontal offset was 39.72 (32.7 to 48.2 mm) compared to 42.89 (26.7 to 50.6 mm) on the normal side. Mean Harris Hip Score (HHS) of 22.64 (14 to 35) improved to 79.43 (68 to 92). Mean pre-operative shortening was 3.95 cm (2 to 8 cm). Residual limb length discrepancy was 1.5 cm (0 to 2 cm). Sciatic neuropraxia in two patients recovered by six months, and femoral neuropraxia in one hip recovered by 12 months. Mean Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was 13.92 (9 to 19). Mean 12-item short form survey (SF-12) physical scores of 50.6 and mental of 60.12 were obtained. Conclusion THA with subtrochanteric shortening is valuable in complex hips with high dislocation. The restoration of the hip centre of rotation and offset is important in these hips. Level of evidence IV Femoral shortening useful in conditions other than DDH and septic sequelae. Restoration of hip centre combined with offset to be planned and ensured.