Toward the realization of a primary low-pressure standard using a superconducting microwave resonator.

We describe a primary gas pressure standard based on the measurement of the refractive index of helium gas using a microwave resonant cavity in the range between 500 Pa and 20 kPa. To operate in this range, the sensitivity of the microwave refractive gas manometer (MRGM) to low-pressure variations is substantially enhanced by a niobium coating of the resonator surface, which becomes superconducting at temperatures below 9 K, allowing one to achieve a frequency resolution of about 0.3 Hz at 5.2 GHz, corresponding to a pressure resolution below 3 mPa at 20 Pa. The determination of helium pressure requires precise thermometry but is favored by the remarkable accuracy achieved by ab initio calculations of the thermodynamic and electromagnetic properties of the gas. The overall standard uncertainty of the MRGM is estimated to be of the order of 0.04%, corresponding to 0.2 Pa at 500 and 8.1 Pa at 20 kPa, with major contributions from thermometry and the repeatability of microwave frequency measurements. A direct comparison of the pressures realized by the MRGM with the reference provided by a traceable quartz transducer shows relative pressure differences between 0.025% at 20 kPa and -1.4% at 500 Pa.

Avasopasem manganese (GC4419) protects against cisplatin-induced chronic kidney disease: An exploratory analysis of renal metrics from a randomized phase 2b clinical trial in head and neck cancer patients.

Head and neck squamous cell carcinoma (HNSCC) patients treated with high-dose cisplatin concurrently with radiotherapy (hdCis-RT) commonly suffer kidney injury leading to acute and chronic kidney disease (AKD and CKD, respectively). We conducted a retrospective analysis of renal function and kidney injury-related plasma biomarkers in a subset of HNSCC subjects receiving hdCis-RT in a double-blinded, placebo-controlled clinical trial (NCT02508389) evaluating the superoxide dismutase mimetic, avasopasem manganese (AVA), an investigational new drug. We found that 90 mg AVA treatment prevented a significant reduction in estimated glomerular filtration rate (eGFR) three months as well as six and twelve months after treatment compared to 30 mg AVA and placebo. Moreover, AVA treatment may have allowed renal repair in the first 22 days following cisplatin treatment as evidenced by an increase in epithelial growth factor (EGF), known to aid in renal recovery. An upward trend was also observed in plasma iron homeostasis proteins including total iron (Fe-blood) and iron saturation (Fe-saturation) in the 90 mg AVA group versus placebo. These data support the hypothesis that treatment with 90 mg AVA mitigates cisplatin-induced CKD by inhibiting hdCis-induced renal changes and promoting renal recovery.

A multicentre, randomised trial comparing schedules of G-CSF (filgrastim) administration for primary prophylaxis of chemotherapy-induced febrile neutropenia in early stage breast cancer.

BACKGROUND: The optimal duration of filgrastim as primary febrile neutropenia (FN) prophylaxis in early breast cancer patients is unknown, with 5, 7 or 10 days being commonly prescribed. This trial evaluates whether 5 days of filgrastim was non-inferior to 7/10 days. PATIENTS AND METHODS: In this randomised, open-label trial, early breast cancer patients who were to receive filgrastim as primary FN prophylaxis were randomly allocated to 5 versus 7 versus 10 days of filgrastim for all chemotherapy cycles. A protocol amendment in November 2017 allowed subsequent patients (N = 324) to be randomised to either 5 or 7/10 days. The primary outcome was a composite of either FN or treatment-related hospitalisations. Secondary outcomes included chemotherapy dose reductions, delays and discontinuations. Analyses were carried out by per protocol (primary) and intention-to-treat, and the non-inferiority margin was set at 3% for the risk of having FN and/or hospitalisation per cycle of chemotherapy. RESULTS: Patients (N = 466) were randomised to receive 5 (184, 39.5%), or 7/10 (282, 60.5%) days of filgrastim. In our primary analysis, the difference in risk of either FN or treatment-related hospitalisation per cycle was -1.52% [95% confidence interval (CI): -3.22% to 0.19%] suggesting non-inferiority of a 5-day filgrastim schedule compared with 7/10-days. The difference in events per cycle for FN was 0.11% (95% CI: -1.05 to 1.27) while for treatment-related hospitalisations it was -1.68% (95% CI: -2.73% to -0.63%). The overall proportions of patients having at least one occurrence of either FN or treatment-related hospitalisation were 11.8% and 14.96% for the 5- and 7/10-day groups, respectively (risk difference: -3.17%, 95% CI: -9.51% to 3.18%). CONCLUSION: Five days of filgrastim was non-inferior to 7/10 days. Given the cost and toxicity of this agent, 5 days should be considered standard of care. CLINICALTRIALS. GOV REGISTRATION: NCT02428114 and NCT02816164.

The Boltzmann project.

The International Committee for Weights and Measures (CIPM), at its meeting in October 2017, followed the recommendation of the Consultative Committee for Units (CCU) on the redefinition of the kilogram, ampere, kelvin and mole. For the redefinition of the kelvin, the Boltzmann constant will be fixed with the numerical value 1.380 649 × 10-23 J K-1. The relative standard uncertainty to be transferred to the thermodynamic temperature value of the triple point of water will be 3.7 × 10-7, corresponding to an uncertainty in temperature of 0.10 mK, sufficiently low for all practical purposes. With the redefinition of the kelvin, the broad research activities of the temperature community on the determination of the Boltzmann constant have been very successfully completed. In the following, a review of the determinations of the Boltzmann constant k, important for the new definition of the kelvin and performed in the last decade, is given.

Improving medical students' written communication skills: design and evaluation of an educational curriculum.

BACKGROUND AND OBJECTIVES: Written and verbal communication skills are important skills for all physicians. While verbal skills are taught and assessed in medical school, medical students report limited instruction in written communication skills. This study examined the impact of a curriculum delivered during a 6-week clinical rotation in Internal Medicine on the objective assessment of medical students' written communication skills. METHODS: The curriculum consisted of two educational programmes: a medical student communication tutorial and a resident feedback workshop. The study was conducted from March 2012 to January 2013 at McMaster University in Hamilton, Ontario, Canada. The study featured three arms: (1) control, (2) medical student communication tutorial alone and (3) student tutorial and resident feedback workshop. Data were collected on 126 students during 6-week Internal Medicine clerkship rotations. Students' written consultation notes were collected prior to the educational programmes and at 6 weeks. Blinded faculty assessors used an independently validated Assessment Checklist to evaluate consultation notes. RESULTS: Consultation note scores improved from week 1 to week 6 across all study arms. However, the change was statistically significant only in arm 3, featuring both the medical student tutorial and the resident feedback workshop, with mean scores improving from 4.75 (SD=1.496) to 5.56 (SD=0.984) out of 7. The mean difference between week 1 and week 6 was significantly different (0.806, p=0.002, 95% CI 0.306 to 1.058). CONCLUSIONS: The combination of a resident feedback workshop with medical student written communication tutorial improves objective evaluations of consultation note scores over student tutorial alone.