The NeST (Neoadjuvant systemic therapy in breast cancer) study: National Practice Questionnaire of United Kingdom multi-disciplinary decision making.

BACKGROUND: Neoadjuvant systemic therapy (NST) is increasingly used in the treatment of breast cancer, yet it is clear that there is significant geographical variation in its use in the UK. This study aimed to examine stated practice across UK breast units, in terms of indications for use, radiological monitoring, pathological reporting of treatment response, and post-treatment surgical management. METHODS: Multidisciplinary teams (MDTs) from all UK breast units were invited to participate in the NeST study. A detailed questionnaire assessing current stated practice was distributed to all participating units in December 2017 and data collated securely usingREDCap. Descriptive statistics were calculated for each questionnaire item. RESULTS: Thirty-nine MDTs from a diverse range of hospitals responded. All MDTs routinely offered neoadjuvant chemotherapy (NACT) to a median of 10% (range 5-60%) of patients. Neoadjuvant endocrine therapy (NET) was offered to a median of 4% (range 0-25%) of patients by 66% of MDTs. The principal indication given for use of neoadjuvant therapy was for surgical downstaging. There was no consensus on methods of radiological monitoring of response, and a wide variety of pathological reporting systems were used to assess tumour response. Twenty-five percent of centres reported resecting the original tumour footprint, irrespective of clinical/radiological response. Radiologically negative axillae at diagnosis routinely had post-NACT or post-NET sentinel lymph node biopsy (SLNB) in 73.0 and 84% of centres respectively, whereas 16% performed SLNB pre-NACT. Positive axillae at diagnosis would receive axillary node clearance at 60% of centres, regardless of response to NACT. DISCUSSION: There is wide variation in the stated use of neoadjuvant systemic therapy across the UK, with general low usage of NET. Surgical downstaging remains the most common indication of the use of NAC, although not all centres leverage the benefits of NAC for de-escalating surgery to the breast and/or axilla. There is a need for agreed multidisciplinary guidance for optimising selection and management of patients for NST. These findings will be corroborated in phase II of the NeST study which is a national collaborative prospective audit of NST utilisation and clinical outcomes.

Search for Sterile Neutrinos in MINOS and MINOS+ Using a Two-Detector Fit.

A search for mixing between active neutrinos and light sterile neutrinos has been performed by looking for muon neutrino disappearance in two detectors at baselines of 1.04 and 735 km, using a combined MINOS and MINOS+ exposure of 16.36×10^{20} protons on target. A simultaneous fit to the charged-current muon neutrino and neutral-current neutrino energy spectra in the two detectors yields no evidence for sterile neutrino mixing using a 3+1 model. The most stringent limit to date is set on the mixing parameter sin^{2}θ_{24} for most values of the sterile neutrino mass splitting Δm_{41}^{2}>10^{-4} eV^{2}.

Establishing an electronic health record-supported approach for outreach to and recruitment of persons at high risk of type 2 diabetes in clinical trials: The vitamin D and type 2 diabetes (D2d) study experience.

AIMS: To establish recruitment approaches that leverage electronic health records in multicenter prediabetes/diabetes clinical trials and compare recruitment outcomes between electronic health record-supported and conventional recruitment methods. METHODS: Observational analysis of recruitment approaches in the vitamin D and type 2 diabetes (D2d) study, a multicenter trial in participants with prediabetes. Outcomes were adoption of electronic health record-supported recruitment approaches by sites, number of participants screened, recruitment performance (proportion screened who were randomized), and characteristics of participants from electronic health record-supported versus non-electronic health record methods. RESULTS: In total, 2423 participants were randomized: 1920 from electronic health record (mean age of 60 years, 41% women, 68% White) and 503 from non-electronic health record sources (mean age of 56.9 years, 58% women, 61% White). Electronic health record-supported recruitment was adopted by 21 of 22 sites. Electronic health record-supported recruitment was associated with more participants screened versus non-electronic health record methods (4969 vs 2166 participants screened), higher performance (38.6% vs 22.7%), and more randomizations (1918 vs 505). Participants recruited via electronic health record were older, included fewer women and minorities, and reported higher use of dietary supplements. Electronic health record-supported recruitment was incorporated in diverse clinical environments, engaging clinicians either at the individual or the healthcare system level. CONCLUSION: Establishing electronic health record-supported recruitment approaches across a multicenter prediabetes/diabetes trial is feasible and can be adopted by diverse clinical environments.

Gender differences in the order of appearance of elbow ossification centres.

BACKGROUND: The predictable order of appearance of elbow secondary ossification centres in children is important in interpreting elbow radiographs, most commonly in the context of trauma. The usual sequence of appearance of these ossification centres is given by the acronym CRITOL, but exceptions have been described and are recognised as normal variants. AIM: To investigate the extent to which the appearance of the elbow secondary ossification centres follows a predictable sequence, and to establish the incidence of exceptions to the usual CRITOL order. METHODS: Two-stage retrospective review of 421 elbow radiographs in children at our centre. RESULTS: Of 64 children with two visible ossification centres, there was a 23% overall variant incidence (49 CR, 15 CI). Twenty-eight children had four visible ossification centres, with an overall variant incidence of 32% (19 CRIT, 9 CRIO). The variants were significantly more common in girls than in boys ( p < 0.001). CONCLUSION: Whilst the majority of radiographs remained consistent with the described CRITOL sequence, variance in this order was seen in a quarter of children with two visible ossification centres, and a third of children with four visible ossification centres. Incidence of variance was much more common in girls, reaching statistical significance. Awareness of these normal variations, particularly in girls, should help to avoid misinterpretation.

Wild, connected, and diverse: building a more resilient system of protected areas.

Current systems of conservation reserves may be insufficient to sustain biodiversity in the face of climate change and habitat losses. Consequently, calls have been made to protect Earth's remaining wildlands and complete the system of protected areas by establishing conservation reserves that (1) better represent ecosystems, (2) increase connectivity to facilitate biota movement in response to stressors including climate change, and (3) promote species persistence within intact landscapes. Using geospatial data, we conducted an assessment for expanding protected areas within the contiguous United States to include the least human-modified wildlands, establish a connected network, and better represent ecosystem diversity and hotspots of biodiversity. Our composite map highlights areas of high value to achieve these goals in the western United States, where existing protected areas and lands with high ecological integrity are concentrated. We also identified important areas in the East rich in species and containing ecosystems that are poorly represented in the existing protected area system. Expanding protection to these priority areas is ultimately expected to create a more resilient system for protecting the nation's biological heritage. This expectation should be subject to rigorous testing prior to implementation, and regional monitoring will ensure areas and actions are adjusted over time.

Strength and performance asymmetry during maximal velocity sprint running.

The aim of this study was to empirically examine the interaction of athlete-specific kinematic kinetic and strength asymmetry in sprint running. Bilateral ground reaction force and kinematic data were collected during maximal velocity (mean = 9.05 m/s) sprinting for eight athletes. Bilateral ground reaction force data were also collected while the same athletes performed maximal effort squat jumps. Using novel composite asymmetry scores, interactions between kinematic and kinetic asymmetry were compared for the group of sprinters. Asymmetry was greater for kinematic variables than step characteristics, with largest respective values of 6.68% and 1.68%. Kinetic variables contained the largest asymmetry values, peaking at >90%. Asymmetry was present in all kinematic and kinetic variables analyzed during sprint trials. However, individual athlete asymmetry profiles were reported for sprint and jump trials. Athletes' sprint performance was not related to their overall asymmetry. Positive relationships were found between asymmetry in ankle work during sprint running and peak vertical force (r = 0.895) and power (r = 0.761) during jump trials, suggesting that the ankle joint may be key in regulating asymmetry in sprinting and highlighting the individual nature of asymmetry. The individual athlete asymmetry profiles and lack of relationship between asymmetry of limb strength and sprint performance suggest that athletes are not "limb dominant" and that strength imbalances are joint and task specific. Compensatory kinetic mechanisms may serve to reduce the effects of strength or biological asymmetry on the performance outcome of step velocity.

Search for Sterile Neutrinos Mixing with Muon Neutrinos in MINOS.

We report results of a search for oscillations involving a light sterile neutrino over distances of 1.04 and 735 km in a ν_{µ}-dominated beam with a peak energy of 3 GeV. The data, from an exposure of 10.56×10^{20} protons on target, are analyzed using a phenomenological model with one sterile neutrino. We constrain the mixing parameters θ_{24} and Δm_{41}^{2} and set limits on parameters of the four-dimensional Pontecorvo-Maki-Nakagawa-Sakata matrix, |U_{µ4}|^{2} and |U_{τ4}|^{2}, under the assumption that mixing between ν_{e} and ν_{s} is negligible (|U_{e4}|^{2}=0). No evidence for ν_{µ}→ν_{s} transitions is found and we set a world-leading limit on θ_{24} for values of Δm_{41}^{2}≲1 eV^{2}.

Combined analysis of νµ disappearance and νµâ†’νe appearance in MINOS using accelerator and atmospheric neutrinos.

We report on a new analysis of neutrino oscillations in MINOS using the complete set of accelerator and atmospheric data. The analysis combines the ν(µ) disappearance and ν(e) appearance data using the three-flavor formalism. We measure |Δm(32)(2)| = [2.28-2.46] × 10(-3) eV(2) (68% C.L.) and sin(2)θ(23) = 0.35-0.65 (90% C.L.) in the normal hierarchy, and |Δm(32)(2)| = [2.32-2.53] × 10(-3) eV(2) (68% C.L.) and sin(2)θ(23) = 0.34-0.67 (90% C.L.) in the inverted hierarchy. The data also constrain δ(CP), the θ(23} octant degeneracy and the mass hierarchy; we disfavor 36% (11%) of this three-parameter space at 68% (90%) C.L.

Well-differentiated papillary mesothelioma: peritoneal implants are not always metastases in the presence of cancer.

INTRODUCTION: Well-differentiated papillary mesothelioma is a rare condition that can cause diagnostic uncertainty. Its appearance resembles metastatic deposits and in the presence of a known primary can often be confused for such. CASE PRESENTATION: In this case, we present a patient who had WDPM in the presence of gastric cancer and emphasise the difficulties in making the diagnosis. CONCLUSION: We highlight the need for a high index of suspicion, biopsies at staging laparoscopy and undertake a review of the literature regarding this uncommon condition.

Measurement of neutrino and antineutrino oscillations using beam and atmospheric data in MINOS.

We report measurements of oscillation parameters from ν(µ) and ν(µ) disappearance using beam and atmospheric data from MINOS. The data comprise exposures of 10.71×10(20) protons on target in the ν(µ)-dominated beam, 3.36×10(20) protons on target in the ν(µ)-enhanced beam, and 37.88 kton yr of atmospheric neutrinos. Assuming identical ν and ν oscillation parameters, we measure |Δm2| = (2.41(-0.10)(+0.09))×10(-3) eV2 and sin2(2θ) = 0.950(-0.036)(+0.035). Allowing independent ν and ν oscillations, we measure antineutrino parameters of |Δm2| = (2.50(-0.25)(+0.23))×10(-3) eV2 and sin2(2θ) = 0.97(-0.08)(+0.03), with minimal change to the neutrino parameters.

Electron neutrino and antineutrino appearance in the full MINOS data sample.

We report on ν(e) and ν(e) appearance in ν(µ) and ν(µ) beams using the full MINOS data sample. The comparison of these ν(e) and ν(e) appearance data at a 735 km baseline with θ13 measurements by reactor experiments probes δ, the θ23 octant degeneracy, and the mass hierarchy. This analysis is the first use of this technique and includes the first accelerator long-baseline search for ν(µ) → ν(e). Our data disfavor 31% (5%) of the three-parameter space defined by δ, the octant of the θ23, and the mass hierarchy at the 68% (90%) C.L. We measure a value of 2sin(2)(2θ13)sin(2)(θ23) that is consistent with reactor experiments.

Neonatal hip septic arthritis: ultrasound should not influence decision to aspirate.

An 18-week-old boy presented to the emergency department with 24-h history of fever and irritability with a painful left hip held in flexion. Blood tests showed an elevated ESR of 65 mm/h, but white cell count and C-reactive protein were in the reference range. Admission hip ultrasound identified a small effusion (<2 mm at the recess), not large enough to determine turbidity. Joint aspiration under general anaesthesia yielded frank pus and mandated open arthrotomy. Physicians must maintain a high index of suspicion of hip septic arthritis irrespective of ultrasound findings and have a low threshold for joint aspiration. Aspiration 'to dryness' would have left substantial pus within the joint and is consistent with advocating arthrotomy and washout in this age group, when the diagnosis of septic arthritis has been made.

Diffusion-weighted magnetic resonance imaging for diagnosis of post-operative paediatric cholesteatoma.

OBJECTIVES: High rates of recidivism are reported after paediatric cholesteatoma surgery. Our practice has adapted to include non-echoplanar diffusion-weighted magnetic resonance imaging for the diagnosis of residual or recurrent cholesteatoma. This audit aimed to evaluate the performance of non-echoplanar diffusion-weighted magnetic resonance imaging in our paediatric population. METHODS: A retrospective review was conducted of non-echoplanar diffusion-weighted magnetic resonance imaging scans performed to detect residual disease or recurrence after surgery for cholesteatoma in children from 1 January 2012 to 30 November 2017 in our centre. Follow-up diffusion-weighted magnetic resonance imaging scans were reviewed to 16 August 2019. RESULTS: Thirty-four diffusion-weighted magnetic resonance imaging scans were included. The sensitivity and specificity values of diffusion-weighted magnetic resonance imaging for detecting post-operative cholesteatoma were 81 per cent and 72 per cent, respectively. Positive predictive and negative predictive values were 72 per cent and 81 per cent, respectively. CONCLUSION: Use of diffusion-weighted magnetic resonance imaging is recommended as a replacement for routine second-look surgical procedures in the paediatric population. However, we would caution that patients require close follow up after negative diffusion-weighted magnetic resonance imaging findings.

Current issues and future directions in gymnastics research: biomechanics, motor control and coaching interface.

The sport of gymnastics is undergoing a global examination of its culture and the relationship between the gymnast, coach and environment is a central focus. The aim of this review is to explore biomechanics and motor control research in skill development and technique selection in artistic gymnastics with a focus on the underlying concepts and scientific principles that allow performance enhancement, skill development and injury risk reduction. The current review examines peer reviewed papers from 2000 onwards, with a focus on contemporary approaches in the field of gymnastics research, and highlights several key directions for future gymnastics research. Based on our review and the integration of the models of Newell (1986) and Irwin et al. (2005), we recommend that future gymnastics research should embrace at the very least a multidisciplinary approach and aim for an interdisciplinary paradigm.

Improved measurement of muon antineutrino disappearance in MINOS.

We report an improved measurement of ν(µ) disappearance over a distance of 735 km using the MINOS detectors and the Fermilab Main Injector neutrino beam in a ν(µ)-enhanced configuration. From a total exposure of 2.95×10(20) protons on target, of which 42% have not been previously analyzed, we make the most precise measurement of Δm2=[2.62(-0.28)(+0.31)(stat)±0.09(syst)]×10(-3) eV2 and constrain the ν(µ) mixing angle sin2(2θ)>0.75 (90% C.L.). These values are in agreement with Δm2 and sin2(2θ) measured for ν(µ), removing the tension reported in [P. Adamson et al. (MINOS), Phys. Rev. Lett. 107, 021801 (2011).].

Lateral condyle fracture of a child's humerus: the radiographic features may be subtle.

Fractures of the lateral condyle of the humerus in children are relatively common and can be easily missed on initial plain radiographs especially in the younger age group. We present a case in which diagnosis of this fracture was delayed for five weeks and therefore presented more challenging surgical management. The salient features that were apparent on the initial radiograph at presentation are discussed as is the use of further imaging techniques that may help to clarify the initial diagnosis. This could significantly reduce the risk of serious complications such as chronic pain, deformity and nerve palsy.

Effects of Vitamin D Supplementation on Insulin Sensitivity and Secretion in Prediabetes.

CONTEXT: Vitamin D regulates glucose homeostasis pathways, but effects of vitamin D supplementation on ß-cell function remain unclear. OBJECTIVE: To investigate the effects of vitamin D3 supplementation on insulin sensitivity and ß-cell function. METHODS: This is a prespecified secondary analysis of the Vitamin D and Type 2 Diabetes study. Overweight/obese adults at high risk for type 2 diabetes (prediabetes) were randomly treated with vitamin D3 4000 IU or matching placebo daily for 24 months. MAIN OUTCOME: Disposition index (DI), as an estimate of ß-cell function, was calculated as the product of Homeostasis Model Assessment 2 indices derived from C-peptide values (HOMA2%Scpep) and C-peptide response during the first 30 minutes of a 75-g oral glucose tolerance test (OGTT). RESULTS: Mean age was 60.5 ± 9.8 years and body mass index was 31.9 ± 4.4 kg/m2. Mean serum 25(OH)D level increased from 27.9 ± 10.3 ng/mL at baseline to 54.9 ng/mL at 2 years in the vitamin D group and was unchanged (28.5 ± 10.0 ng/mL) in the placebo group. The baseline DI predicted incident diabetes independent of the intervention. In the entire cohort, there were no significant differences in changes in DI, HOMA2%Scpep, or C-peptide response between the 2 groups. Among participants with baseline 25(OH)D level <12 ng/mL, the mean percent differences for DI between the vitamin D and placebo groups was 8.5 (95% CI, 0.2-16.8). CONCLUSIONS: Supplementation with vitamin D3 for 24 months did not improve an OGTT-derived index of ß-cell function in people with prediabetes not selected based on baseline vitamin D status; however, there was benefit among those with very low baseline vitamin D status.

Measurement of the neutrino mass splitting and flavor mixing by MINOS.

Measurements of neutrino oscillations using the disappearance of muon neutrinos from the Fermilab NuMI neutrino beam as observed by the two MINOS detectors are reported. New analysis methods have been applied to an enlarged data sample from an exposure of 7.25×10(20) protons on target. A fit to neutrino oscillations yields values of |Δm(2)|=(2.32(-0.08)(+0.12))×10(-3) eV(2) for the atmospheric mass splitting and sin(2)(2θ)>0.90 (90% C.L.) for the mixing angle. Pure neutrino decay and quantum decoherence hypotheses are excluded at 7 and 9 standard deviations, respectively.

Active to sterile neutrino mixing limits from neutral-current interactions in MINOS.

Results are reported from a search for active to sterile neutrino oscillations in the MINOS long-baseline experiment, based on the observation of neutral-current neutrino interactions, from an exposure to the NuMI neutrino beam of 7.07×10(20) protons on target. A total of 802 neutral-current event candidates is observed in the Far Detector, compared to an expected number of 754 ± 28(stat) ± 37(syst) for oscillations among three active flavors. The fraction f(s) of disappearing ν(µ) that may transition to ν(s) is found to be less than 22% at the 90% C.L.

First direct observation of muon antineutrino disappearance.

This Letter reports the first direct observation of muon antineutrino disappearance. The MINOS experiment has taken data with an accelerator beam optimized for ν(µ) production, accumulating an exposure of 1.71 × 10²° protons on target. In the Far Detector, 97 charged current ν(µ) events are observed. The no-oscillation hypothesis predicts 156 events and is excluded at 6.3σ. The best fit to oscillation yields |Δm²| = [3.36(-0.40)(+0.46)(stat) ± 0.06(syst)] × 10⁻³ eV², sin²(2θ) = 0.86(-0.12)(+0.11)(stat) ± 0.01(syst). The MINOS ν(µ) and ν(µ) measurements are consistent at the 2.0% confidence level, assuming identical underlying oscillation parameters.