NTCP modeling and dose-volume correlations for acute xerostomia and dry eye after whole brain radiation.

BACKGROUND: Whole brain radiation (WBRT) may lead to acute xerostomia and dry eye from incidental parotid and lacrimal exposure, respectively. We performed a prospective observational study to assess the incidence/severity of this toxicity. We herein perform a secondary analysis relating parotid and lacrimal dosimetric parameters to normal tissue complication probability (NTCP) rates and associated models. METHODS: Patients received WBRT to 25-40 Gy in 10-20 fractions using 3D-conformal radiation therapy without prospective delineation of the parotids or lacrimals. Patients completed questionnaires at baseline and 1 month post-WBRT. Xerostomia was assessed using the University of Michigan xerostomia score (scored 0-100, toxicity defined as ≥ 20 pt increase) and xerostomia bother score (scored from 0 to 3, toxicity defined as ≥ 2 pt increase). Dry eye was assessed using the Subjective Evaluation of Symptom of Dryness (SESoD, scored from 0 to 4, toxicity defined as ≥ 2 pt increase). The clinical data were fitted by the Lyman-Kutcher-Burman (LKB) and Relative Seriality (RS) NTCP models. RESULTS: Of 55 evaluable patients, 19 (35%) had ≥ 20 point increase in xerostomia score, 11 (20%) had ≥ 2 point increase in xerostomia bother score, and 13 (24%) had ≥ 2 point increase in SESoD score. For xerostomia, parotid V10Gy-V20Gy correlated best with toxicity, with AUC 0.68 for xerostomia score and 0.69-0.71 for bother score. The values for the D50, m and n parameters of the LKB model were 22.3 Gy, 0.84 and 1.0 for xerostomia score and 28.4 Gy, 0.55 and 1.0 for bother score, respectively. The corresponding values for the D50, γ and s parameters of the RS model were 23.5 Gy, 0.28 and 0.0001 for xerostomia score and 32.0 Gy, 0.45 and 0.0001 for bother score, respectively. For dry eye, lacrimal V10Gy-V15Gy were found to correlate best with toxicity, with AUC values from 0.67 to 0.68. The parameter values of the LKB model were 53.5 Gy, 0.74 and 1.0, whereas of the RS model were 54.0 Gy, 0.37 and 0.0001, respectively. CONCLUSIONS: Xerostomia was most associated with parotid V10Gy-V20Gy, and dry eye with lacrimal V10Gy-V15Gy. NTCP models were successfully created for both toxicities and may help clinicians refine dosimetric goals and assess levels of risk in patients receiving palliative WBRT.

Probing gravity by holding atoms for 20 seconds.

Atom interferometers are powerful tools for both measurements in fundamental physics and inertial sensing applications. Their performance, however, has been limited by the available interrogation time of freely falling atoms in a gravitational field. By suspending the spatially separated atomic wave packets in a lattice formed by the mode of an optical cavity, we realize an interrogation time of 20 seconds. Our approach allows gravitational potentials to be measured by holding, rather than dropping, atoms. After seconds of hold time, gravitational potential energy differences from as little as micrometers of vertical separation generate megaradians of interferometer phase. This trapped geometry suppresses the phase variance due to vibrations by three to four orders of magnitude, overcoming the dominant noise source in atom-interferometric gravimeters.

Use of the Consultation Letter Rating Scale among Geriatric Medicine Postgraduate Trainees.

OBJECTIVES: The implementation of competency-based evaluations increases the emphasis on in-training assessment. The Consultation Letter Rating Scale (CLRS), published by the Royal College of Physicians and Surgeons of Canada, is a tool that assesses written-communication competencies. This multisite project evaluated the tool's validity, reliability, feasibility, and acceptability for use in postgraduate geriatric medicine training. METHODS: Geriatric medicine trainees provided consultation letters from the 2017-2018 academic year. Geriatricians reviewed a standardized module and completed the tool for all the deidentified letters. The reviewers recorded the time used to complete the tool for each letter and completed a survey on content validity. Trainees completed a survey on the tool's usefulness. Responses were reviewed independently by two authors for thematic content. The unweighted and the weighted κ were used to measure interrater reliability. RESULTS: A total of 10 of 11 (91%) eligible trainees each provided five letters that were reviewed independently by six geriatricians, leading to a total of 300 assessments. A very small portion (4% [N = 12]) of assessments was incomplete. An average of 4.82 minutes (standard deviation = 3.17) was used to complete the tool. There was high interrater agreement for overall scores, with a multiple-rater weighted κ of 83% (95% confidence interval = 76%-89%). The interrater agreement was lower for the individual components. Both raters and trainees found the comments more useful than the numerical ratings. CONCLUSIONS: Our results support the use of the CLRS for facilitating feedback on the quality of consult letters to improve written-communication competencies among geriatric medicine trainees. J Am Geriatr Soc 67:2157-2160, 2019.

Efficient Adiabatic Spin-Dependent Kicks in an Atom Interferometer.

We present an atom interferometry technique in which the beam splitter is split into two separate operations. A microwave pulse first creates a spin-state superposition, before optical adiabatic passage spatially separates the arms of that superposition. Despite using a thermal atom sample in a small (600 µm) interferometry beam, this procedure delivers an efficiency of 99% per ℏk of momentum separation. Utilizing this efficiency, we first demonstrate interferometry with up to 16ℏk momentum splitting and free-fall limited interrogation times. We then realize a single-source gradiometer, in which two interferometers measuring a relative phase originate from the same atomic wave function. Finally, we demonstrate a resonant interferometer with over 100 adiabatic passages, and thus over 400ℏk total momentum transferred.

Selective Blockade of T-Type Ca2+ Channels is Protective Against Alcohol-Withdrawal Induced Seizure and Mortality.

AIMS: We have previously demonstrated that blockade of T-type calcium channels by the non-selective antagonist, ethosuximide (ETX), is effective at reducing electrographical and behavioral correlates of alcohol-withdrawal (WD) seizure. Here, we investigated whether blockade of these calcium channels with the selective antagonist TTA-P2 also reduces alcohol-WD seizure. SHORT SUMMARY: The non-specific T-type calcium channel antagonist, ETX, is protective against alcohol-WD seizure. However, the mechanism of this effect is unclear. Here, we provide evidence that further suggests selective blockade of T-type calcium channels are protective against alcohol-WD seizure and WD-related mortality. METHODS: We used an intermittent ethanol exposure model to produce WD-induced hyperexcitability in DBA/2 J mice. Seizure severity was intensified with the chemoconvulsant pentylenetetrazole (PTZ). RESULTS: TTA-P2 (10 mg/kg) reduced seizure severity in mice undergoing alcohol WD with concurrent PTZ treatment (20 mg/kg). Moreover, TTA-P2 (20 and 40 mg/kg) was also protective against PTZ-induced (40 mg/kg) seizure and mortality. CONCLUSIONS: These results are consistent with prior results using ETX, and suggest that the protective effects of ETX and TTA-P2 against EtOH WD seizures are mediated by T-type calcium channels.

A Challenging Diagnosis of IgG4-Related Disease When Understanding Limitations of Laboratory Testing Was Pivotal.

A 76-year-old man was incidentally found on a CT scan to have lymphadenopathy and bilateral kidney enlargement suggestive of infiltrative renal disease. He was largely asymptomatic but had bilateral salivary and lacrimal gland enlargement. A grossly elevated serum IgG (>70 g/L) with concomitant suppression of other immunoglobulins, a small IgG restriction, and a parotid biopsy revealing lymphoplasmacytic infiltrate with slight kappa light chain excess all suggested a lymphoproliferative disorder (LPD). The diagnostic workup was further confounded by a normal serum IgG4 concentration. Moreover, bone marrow and renal biopsies did not reveal evidence of LPD. Discussion with the laboratory not only clarified that the markedly increased total IgG could not be accounted for by the small IgG restriction, but also identified a discrepancy in the IgG4 measurement. Repeat analysis of a follow-up sample revealed an elevated IgG4 of 5.94 (reference interval: 0.039-0.864) g/L, which prompted a repeat parotid biopsy that showed predominant IgG4+ lymphocytic infiltrates. Despite the deluding presentations, a final diagnosis of IgG4-related disease (IgG4-RD) was made based on elevated serum IgG4 concentrations and histopathological findings. This case highlights the importance of recognizing limitations of laboratory testing and the benefit of close communications among clinical subspecialties and the laboratory.

Validation of a Food Frequency Questionnaire for Bone Nutrients in Pregnant Women.

PURPOSE: The aim was to validate a food frequency questionnaire (FFQ) against a 3-day food record (3DFR) for pregnant women with a focus on nutrients important for bone health from food and supplements. METHODS: The FFQ and 3DFR were administered to pregnant women (n = 42) aged 18-45 years in their third trimester of pregnancy in Hamilton, Ontario. Nutrient analysis of intakes was conducted using an FFQ calculator and Nutritionist-Pro software. The average daily serving consumption of Milk and alternatives group and Vegetable subgroup from Canada's Food Guide were also compared. RESULTS: There was a high positive correlation between methods for total dietary vitamin D (r = 0.83). Low positive associations were observed for total protein (r = 0.37), calcium (r = 0.36), vitamin K (r = 0.41), and servings of Milk and alternatives (r = 0.36). A cross-classification analysis using participants' intake quartiles revealed no major misclassifications. Bland-Altman analysis showed that the FFQ mildly underestimated the intake for protein, whereas it grossly overestimated the intake of vitamin K, and daily servings of Milk and alternatives and Vegetable. CONCLUSIONS: This FFQ can serve as a useful tool in clinical and research settings to assess key bone nutrients from foods and supplement sources in pregnant women.

Ethosuximide Reduces Mortality and Seizure Severity in Response to Pentylenetetrazole Treatment During Ethanol Withdrawal.

AIMS: We recently demonstrated that T-type calcium channels are affected by alcohol abuse and withdrawal. Treatment with ethosuximide, an antiepileptic drug that blocks T-type calcium channels, reduces seizure activity induced by intermittent ethanol exposures and withdrawals. Here, we expand on these findings to test whether ethosuximide can reduce the sensitivity to pentylenetetrazole-induced seizures during ethanol withdrawal. METHODS: We used an intermittent ethanol exposure model to produce withdrawal-induced hyperexcitability in DBA/2J mice. RESULTS: Ethosuximide (250 mg/kg) reduced seizure severity in mice undergoing ethanol withdrawal with concurrent PTZ treatment (20 mg/kg). Importantly, ethosuximide did not produce rebound excitability and protected against ethanol withdrawal-induced mortality produced by concurrent PTZ treatment (40 mg/kg). CONCLUSION: These results, in addition to previous preclinical findings, suggest that ethosuximide should be further evaluated as a safe, effective alternative to benzodiazepines for the treatment of alcohol withdrawal.

Pre-Clerkship Observerships to Increase Early Exposure to Geriatric Medicine.

BACKGROUND AND PURPOSE: To foster interest in geriatric care, the Queen's Geriatrics Interest Group (QGIG) collaborated with the Division of Geriatric Medicine to arrange a Geriatrics Pre-Clerkship Observership Program. METHODS: Forty-two pre-clerkship medical students participated in the program between October 2013 and May 2014. Participants were paired with a resident and/or attending physician for a four-hour weekend observership on an inpatient geriatric rehabilitation unit. The program was assessed using: (1) internally developed Likert scales assessing student's experiences and interest in geriatric medicine before and after the observership; (2) University of California Los Angeles-Geriatric Attitudes Scale (UCLA-GAS); and (3) narrative feedback. RESULTS: All participants found the process of setting up the observership easy. Some 72.7% described the observership experience as leading to positive changes in their attitude toward geriatric medicine and 54.5% felt that it stimulated their interest in the specialty. No statistically significant change in UCLA-GAS scores was detected (mean score pre- versus post-observership: 3.5 ± 0.5 versus 3.7 ± 0.4; p=.35). All participants agreed that the program should continue, and 90% stated that they would participate again. CONCLUSIONS: The observership program was positively received by students. Structured pre-clerkship observerships may be a feasible method for increasing exposure to geriatric medicine.