The Influence of Fat Suppression Technique on Diffusion-weighted (DW) MRI in Lung Cancer

Purpose: To qualitatively and quantitatively investigate the effect of common vendor-related sequence variations in fat suppression techniques on the diagnostic performance of free-breathing DW protocols for lung imaging.Methods: 8 patients with malignant lung lesions were scanned in free breathing using two diffusion-weighted (DW) protocols with different fat suppression techniques: DWA used short-tau inversion recovery (STIR), and DWB used Spectral Adiabatic Inversion Recovery (SPAIR). Both techniques were obtained at two time points, between 1 hour and 1 week apart. Image quality was assessed using a 5-point scoring system. The number of lesions visible within lung, mediastinum and at thoracic inlet on the DW (b=800 s/mm2) images was compared. Signal-to-noise ratios (SNR) were calculated for lesions and para-spinal muscle. Repeatability of ADC values of the lesions was estimated for both protocols together and separately.Results: There was a signal void at the thoracic inlet in all patients with DWB but not with DWA. DWA images were rated significantly better than DWB images overall quality domains. (Cohens κ = 1). Although 8 more upper mediastinal/thoracic inlet lymph nodes were detected with DWA than DWB, this did not reach statistical significance (p = 0.23). Tumour ADC values were not significantly different between protocols (p=0.93), their ADC reproducibility was satisfactory (CoV=7.7%) and repeatability of each protocol separately was comparable (CoVDWA=3.7% (95% CI 2.5 7.1%) and CoVDWB=4.6% (95% CI 3.18.8%)).Conclusion: In a free-breathing DW-MRI protocol for lung, STIR fat suppression produced images of better diagnostic quality than SPAIR, while maintaining comparable SNR and providing repeatable quantitative ADC acceptable for use in a multicentre trial setting

Nonadiabatic effects in a generalized Jahn-Teller lattice model: heavy and light polarons, pairing and metal-insulator transition

The ground state polaron potential of 1D lattice of two-level molecules with spinless electrons and two Einstein phonon modes with quantum phonon-assisted transitions between the levels is found anharmonic in phonon displacements. The potential shows a crossover from two nonequivalent broad minima to a single narrow minimum corresponding to the level positions in the ground state. Generalized variational approach implies prominent nonadiabatic effects:(i) In the limit of the symmetric E-e Jahn- Teller situation they cause transition between the regime of the predominantly one-level "heavy" polaron and a "light" polaron oscillating between the levels due to phonon assistance with almost vanishing polaron displacement. It implies enhancement of the electron transfer due to decrease of the "heavy" polaron mass (undressing) at the point of the transition. Pairing of "light" polarons due to exchange of virtual phonons occurs. Continuous transition to new energy ground state close to the transition from "heavy" polaron phase to "light" (bi)polaron phase occurs. In the "heavy" phase, there occurs anomalous (anharmonic) enhancements of quantum fluctuations of the phonon coordinate, momentum and their product as functions of the effective coupling. (ii) Dependence of the polaron mass on the optical phonon frequency appears.(iii) Rabi oscillations significantly enhance quantum shift of the insulator-metal transition line to higher values of the critical effective e-ph coupling supporting so the metallic phase. In the E-e JT case, insulator-metal transition coincide with the transition between the "heavy" and the "light" (bi)polaron phase at certain (strong) effective e-ph interaction.Comment: Paper in LaTex format (file jtseptx.tex) and 9 GIF-figures (ppic_1.gif,...ppic_9.gif

A qualitative study of health care professionals' views and experiences of paediatric advance care planning

Background Good end-of-life care planning is vital to ensure optimal care is provided for patients and their families. Two key factors are open and honest advance care planning conversations between the patient (where possible), family, and health care professionals, focusing on exploring what their future wishes are; and the development of an advance care plan document. However, in paediatric and neonatal settings, there has been little research to demonstrate how advance care planning conversations take place. This study explored health care professionals’ views and experiences of paediatric advance care planning in hospitals, community settings and hospices. MethodsA qualitative methodology was employed using purposive sampling of health care professionals involved in the end-of-life care for children aged 0–18 years known to the hospital palliative care team, and had died at least three months before, but less than 18 months prior to the study. Ethics committee approval was obtained for the study. Located in the North of England, the study involved three hospitals, a children’s hospice, and community services. Data were collected using semi-structured, digitally recorded, telephone interviews. All interviews were transcribed verbatim and subjected to thematic analysis. ResultsTwenty-one health care professionals participated, including generalist paediatric staff as well as specialist palliative care staff.Two themes were generated from the study: The timing of planning conversations, including waiting for the relationship with the family to form; the introduction of parallel planning; avoiding a crisis situation. Secondly, supporting effective conversations around advance care planning, including where to have the conversation; introducing the conversation; and how to approach the topic encompassing the value of advance care planning and documentation for families. Conclusion The timing of when to start the advance care planning conversations remains an issue for health care professionals. The value of doing it in stages and considering the environment where the conversations are held was noted. Timely planning was seen as vital to avoid difficult conversations at a crisis point and for co-ordination of care. Good advance care planning is to provide the best person-centred care for the child and experience for the family

Phase I study of IMGN901, a CD56-targeting antibody-drug conjugate, in patients with CD56-positive solid tumors.

Background IMGN901 is a CD56-targeting antibody-drug conjugate designed for tumor-selective delivery of the cytotoxic maytansinoid DM1. This phase 1 study investigated the safety, tolerability, pharmacokinetics, and preliminary activity of IMGN901 in patients with CD56-expressing solid tumors. Methods Patients were enrolled in cohorts of escalating IMGN901 doses, administered intravenously, on 3 consecutive days every 21 days. A dose-expansion phase accrued patients with small cell lung cancer (SCLC), Merkel cell carcinoma (MCC), or ovarian cancer. Results Fifty-two patients were treated at doses escalating from 4 to 94 mg/m(2)/day. The maximum tolerated dose (MTD) was determined to be 75 mg/m(2). Dose-limiting toxicities included fatigue, neuropathy, headache or meningitis-like symptoms, chest pain, dyspnea, and myalgias. In the dose-expansion phase (n = 45), seven patients received 75 mg/m(2) and 38 received 60 mg/m(2) for up to 21 cycles. The recommended phase 2 dose (RP2D) was established at 60 mg/m(2) during dose expansion. Overall, treatment-emergent adverse events (TEAEs) were experienced by 96.9 % of all patients, the majority of which were Grade 1 or 2. The most commonly reported Grade 3 or 4 TEAEs were hyponatremia and dyspnea (each 8.2 %). Responses included 1 complete response (CR), 1 clinical CR, and 1 unconfirmed partial response (PR) in MCC; and 1 unconfirmed PR in SCLC. Stable disease was seen for 25 % of all evaluable patients who received doses ≥60 mg/m(2). Conclusions The RP2D for IMGN901 of 60 mg/m(2) administered for 3 consecutive days every 3 weeks was associated with an acceptable tolerability profile. Objective responses were observed in patients with advanced CD56+ cancers

Etiology of hospital mortality in children living in low- and middle-income countries:a systematic review and meta-analysis

In 2019, 80% of the 7.4 million global child deaths occurred in low- and middle-income countries (LMICs). Global and regional estimates of cause of hospital death and admission in LMIC children are needed to guide global and local priority setting and resource allocation but are currently lacking. The study objective was to estimate global and regional prevalence for common causes of pediatric hospital mortality and admission in LMICs. We performed a systematic review and meta-analysis to identify LMIC observational studies published January 1, 2005-February 26, 2021. Eligible studies included: a general pediatric admission population, a cause of admission or death, and total admissions. We excluded studies with data before 2,000 or without a full text. Two authors independently screened and extracted data. We performed methodological assessment using domains adapted from the Quality in Prognosis Studies tool. Data were pooled using random-effects models where possible. We reported prevalence as a proportion of cause of death or admission per 1,000 admissions with 95% confidence intervals (95% CI). Our search identified 29,637 texts. After duplicate removal and screening, we analyzed 253 studies representing 21.8 million pediatric hospitalizations in 59 LMICs. All-cause pediatric hospital mortality was 4.1% [95% CI 3.4%–4.7%]. The most common causes of mortality (deaths/1,000 admissions) were infectious [12 (95% CI 9–14)]; respiratory [9 (95% CI 5–13)]; and gastrointestinal [9 (95% CI 6–11)]. Common causes of admission (cases/1,000 admissions) were respiratory [255 (95% CI 231–280)]; infectious [214 (95% CI 193–234)]; and gastrointestinal [166 (95% CI 143–190)]. We observed regional variation in estimates. Pediatric hospital mortality remains high in LMICs. Global child health efforts must include measures to reduce hospital mortality including basic emergency and critical care services tailored to the local disease burden. Resources are urgently needed to promote equity in child health research, support researchers, and collect high-quality data in LMICs to further guide priority setting and resource allocation

Postpartum-specific anxiety as a predictor of infant-feeding outcomes and perceptions of infant-feeding behaviours: new evidence for childbearing specific measures of mood

Studies of pregnancy-specific anxiety suggest that it is a distinct construct which predicts perinatal outcomes more effectively than other general measures of anxiety. In response, a novel measure of postpartum-specific anxiety (PSAS) has been developed and validated, but it is not yet clear whether it possesses the same predictive power as its pregnancy-specific counterparts. The aim of this short-term prospective study was to (a) test the predictive validity of the PSAS in the context of one specific perinatal outcome, infant-feeding, and (b) examine whether the PSAS may be more efficacious at predicting infant-feeding outcomes and behaviours than the more commonly used general measures. Eight hundred mothers of infants aged between 0 and 6 months completed the PSAS alongside general measures of anxiety and depression at baseline. A subsample (n = 261) returned to complete a follow-up questionnaire examining infant-feeding outcomes and behaviours two weeks later. Hierarchical regression models revealed that the PSAS was associated with lower odds of breastfeeding exclusively, and breastfeeding in any quantity in the first 6 months postpartum. PSAS scores were also significantly associated with infant-feeding behaviours including a lower perceived enjoyment of food, and greater perceived food responsiveness and satiety responsiveness in the infant. As hypothesised, the PSAS was a stronger predictor of infant-feeding outcomes and behaviours than general anxiety and depression. The findings provide evidence for the predictive validity of the PSAS and call for the use of childbearing specific measures of mood when attempting to predict perinatal outcomes. Replication of these findings across other indices of maternal and infant health is now necessary

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic