Survival prediction in mesothelioma using a scalable lasso regression model: instructions for use and initial performance using clinical predictors

Introduction: Accurate prognostication is difficult in malignant pleural mesothelioma (MPM). We developed a set of robust computational models to quantify the prognostic value of routinely available clinical data, which form the basis of published MPM prognostic models. Methods: Data regarding 269 patients with MPM were allocated to balanced training (n=169) and validation sets (n=100). Prognostic signatures (minimal length best performing multivariate trained models) were generated by least absolute shrinkage and selection operator regression for overall survival (OS), OS <6 months and OS <12 months. OS prediction was quantified using Somers DXY statistic, which varies from 0 to 1, with increasing concordance between observed and predicted outcomes. 6-month survival and 12-month survival were described by area under the curve (AUC) scores. Results: Median OS was 270 (IQR 140–450) days. The primary OS model assigned high weights to four predictors: age, performance status, white cell count and serum albumin, and after cross-validation performed significantly better than would be expected by chance (mean DXY0.332 (±0.019)). However, validation set DXY was only 0.221 (0.0935–0.346), equating to a 22% improvement in survival prediction than would be expected by chance. The 6-month and 12-month OS signatures included the same four predictors, in addition to epithelioid histology plus platelets and epithelioid histology plus C-reactive protein (mean AUC 0.758 (±0.022) and 0.737 (±0.012), respectively). The <6-month OS model demonstrated 74% sensitivity and 68% specificity. The <12-month OS model demonstrated 63% sensitivity and 79% specificity. Model content and performance were generally comparable with previous studies. Conclusions: The prognostic value of the basic clinical information contained in these, and previously published models, is fundamentally of limited value in accurately predicting MPM prognosis. The methods described are suitable for expansion using emerging predictors, including tumour genomics and volumetric staging

Tropical cyclone perceptions, impacts and adaptation in the Southwest Pacific: an urban perspective from Fiji, Vanuatu and Tonga

The destruction caused by tropical cyclone (TC) Pam in March 2015 is considered one of the worst natural disasters in the history of Vanuatu. It has highlighted the need for a better understanding of TC impacts and adaptation in the Southwest Pacific (SWP) region. Therefore, the key aims of this study are to (i) understand local perceptions of TC activity, (ii) investigate impacts of TC activity and (iii) uncover adaptation strategies used to offset the impacts of TCs. To address these aims, a survey (with 130 participants from urban areas) was conducted across three SWP small island states (SISs): Fiji, Vanuatu and Tonga (FVT). It was found that respondents generally had a high level of risk perception and awareness of TCs and the associated physical impacts, but lacked an understanding of the underlying weather conditions. Responses highlighted that current methods of adaptation generally occur at the local level, immediately prior to a TC event (preparation of property, gathering of food, finding a safe place to shelter). However higher level adaptation measures (such as the modification to building structures) may reduce vulnerability further. Finally, we discuss the potential of utilising weather-related traditional knowledge and non-traditional knowledge of empirical and climate-model-based weather forecasts to improve TC outlooks, which would ultimately reduce vulnerability and increase adaptive capacity. Importantly, lessons learned from this study may result in the modification and/or development of existing adaptation strategies

Doctors are inconsistent in estimating survival after CPR and are not using such predictions consistently in determining DNACPR decisions

Background: It is unclear whether doctors base their resuscitation decisions solely on their perceived outcome. Through the use of theoretical scenarios, we aimed to examine the ‘do not attempt cardiopulmonary resuscitation’ (DNACPR) decision-making. Methods: A questionnaire survey was sent to consultants and specialty trainees across two Norfolk (UK) hospitals during December 2013. The survey included demographic questions and six clinical scenarios with varying prognosis. Participants were asked if they would resuscitate the patient or not. Identical scenarios were then shown in a different order and doctors were asked to quantify patients’ estimated chance of survival. Results: A total of 137 individuals (mean age 41 years (SD 7.9%)) responded. The response rate was 69%. Approximately 60% were consultants. We found considerable variation in clinician estimates of median chance of survival. In three out of six of our scenarios, the survival estimated varied from <1% to 95%. There was a statistically significant difference identified in the estimated median survival between those clinicians who would or would not resuscitate in four of the six scenarios presented. Conclusion: This study has highlighted the wide variation between clinicians in their estimates of likely survival and little concordance between clinicians over their resuscitation decisions. The diversity in clinician decision-making should be explored further

Electrochemical Characterization of Self-Assembled Monolayers on Gold Substrates Derived from Thermal Decomposition of Monolayer-Protected Cluster Films

Networked films of monolayer-protected clusters (MPCs), alkanethiolate-stabilized gold nanoparticles, can be thermally decomposed to form stable gold on glass substrates that are subsequently modified with self-assembled monolayers (SAMs) for use as modified electrodes. Electrochemical assessment of these SAM-modified gold substrates, including double-layer capacitance measurements, linear sweep desorption of the alkanethiolates, and diffusional redox probing, all show that SAMs formed on gold supports formed from thermolysis of MPC films possess substantially higher defect density compared to SAMs formed on traditional evaporated gold. The density of defects in the SAMs on thermolyzed gold is directly related to the strategies used to assemble the MPC film prior to thermolysis. Specifically, gold substrates formed from thermally decomposing MPC films formed with electrostatic bridges between carboxylic acid-modified MPCs and metal ion linkers are particularly sensitive to the degree of metal exposure during the assembly process. While specific metal dependence was observed, metal concentration within the MPC precursor film was determined to be a more significant factor. Specific MPC film linking strategies and pretreatment methods that emphasized lower metal exposure resulted in gold films that supported SAMs of lower defect density. The defect density of a SAM-modified electrode is shown to be critical in certain electrochemical experiments such as protein monolayer electrochemistry of adsorbed cytochrome c. While the thermal decomposition of nanoparticle film assemblies remains a viable and interesting technique for coating both flat and irregular shaped substrates, this study provides electrochemical assessment tools and tactics for determining and controlling SAM defect density on this type of gold structure, a property critical to their effective use in subsequent electrochemical applications

Chest drain aerosol generation in COVID-19 and emission reduction using a simple anti-viral filter

Introduction: The COVID-19 pandemic has been characterised by significant in-hospital virus transmission and deaths among healthcare workers. Sources of in-hospital transmission are not fully understood, with special precautions currently reserved for procedures previously shown to generate aerosols (particles &lt;5 μm). Pleural procedures are not currently considered AGPs (Aerosol Generating Procedures), reflecting a lack of data in this area. Methods: An underwater seal chest drain bottle (R54500, Rocket Medical UK) was set up inside a 60-litre plastic box and connected via an airtight conduit to a medical air supply. A multichannel particle counter (TSI Aerotrak 9310 Aerosol Monitor) was placed inside the box, allowing measurement of particle count/cubic foot (pc/ft3) within six channel sizes: 0.3–0.5, 0.5–1, 1–3, 3–5, 5–10 and &gt;10 μm. Stabilised particle counts at 1, 3 and 5 L/min were compared by Wilcoxon signed rank test; p values were Bonferroni-adjusted. Measurements were repeated with a simple anti-viral filter, designed using repurposed materials by the study team, attached to the drain bottle. The pressure within the bottle was measured to assess any effect of the filter on bottle function. Results: Aerosol emissions increased with increasing air flow, with the largest increase observed in smaller particles (0.3–3 μm). Concentration of the smallest particles (0.3–0.5 μm) increased from background levels by 700, 1400 and 2500 pc/ft3 at 1, 3 and 5 L/min, respectively. However, dispersion of particles of all sizes was effectively prevented by use of the viral filter at all flow rates. Use of the filter was associated with a maximum pressure rise of 0.3 cm H2O after 24 hours of flow at 5 L/min, suggesting minimal impact on drain function. Conclusion: A bubbling chest drain is a source of aerosolised particles, but emission can be prevented using a simple anti-viral filter. These data should be considered when designing measures to reduce in-hospital spread of SARS-CoV-2

A Multi-Institutional Analysis of Adjuvant Chemotherapy and Radiation Sequence in Women With Stage IIIC Endometrial Cancer

PURPOSE: Our purpose was to evaluate the effect of sequence and type of adjuvant therapy for patients with stage IIIC endometrial carcinoma (EC) on outcomes. METHODS AND MATERIALS: In a multi-institutional retrospective cohort study, patients with stage IIIC EC who had surgical staging and received both adjuvant chemotherapy and radiation therapy (RT) were included. Adjuvant treatment regimens were classified as adjuvant chemotherapy followed by sequential RT (upfront chemo), which was predominant sequence; RT with concurrent chemotherapy followed by chemotherapy (concurrent); systemic chemotherapy before and after RT (sandwich); adjuvant RT followed by chemotherapy (upfront RT); or chemotherapy concurrent with vaginal cuff brachytherapy alone (chemo-brachy). Overall survival (OS) and recurrence-free survival (RFS) rates were estimated by the Kaplan-Meier method. RESULTS: A total of 686 eligible patients were included with a median follow-up of 45.3 months. The estimated 5-year OS and RFS rates were 74% and 66%, respectively. The sequence and type of adjuvant therapy were not correlated with OS or RFS (adjusted P = .68 and .84, respectively). On multivariate analysis, black race, nonendometrioid histology, grade 3 tumor, stage IIIC2, and presence of adnexal and cervical involvement were associated with worse OS and RFS (all P \u3c .05). Regardless of the sequence of treatment, the most common site of first recurrence was distant metastasis (20.1%). Vaginal only, pelvic only, and paraortic lymph node (PALN) recurrences occurred in 11 (1.6%),15 (2.2 %), and 43 (6.3 %) patients, respectively. Brachytherapy alone was associated with a higher rate of PALN recurrence (15%) compared with external beam radiation therapy (5%) P \u3c .0001. CONCLUSIONS: The sequence and type of combined adjuvant therapy did not affect OS or RFS rates. Brachytherapy alone was associated with a higher rate of PALN recurrence, emphasizing the role of nodal radiation for stage IIIC EC. The vast proportion of recurrences were distant despite systemic chemotherapy, highlighting the need for novel regimens

A global view of the OCA2-HERC2 region and pigmentation

Mutations in the gene OCA2 are responsible for oculocutaneous albinism type 2, but polymorphisms in and around OCA2 have also been associated with normal pigment variation. In Europeans, three haplotypes in the region have been shown to be associated with eye pigmentation and a missense SNP (rs1800407) has been associated with green/hazel eyes (Branicki et al. in Ann Hum Genet 73:160–170, 2009). In addition, a missense mutation (rs1800414) is a candidate for light skin pigmentation in East Asia (Yuasa et al. in Biochem Genet 45:535–542, 2007; Anno et al. in Int J Biol Sci 4, 2008). We have genotyped 3,432 individuals from 72 populations for 21 SNPs in the OCA2-HERC2 region including those previously associated with eye or skin pigmentation. We report that the blue-eye associated alleles at all three haplotypes were found at high frequencies in Europe; however, one is restricted to Europe and surrounding regions, while the other two are found at moderate to high frequencies throughout the world. We also observed that the derived allele of rs1800414 is essentially limited to East Asia where it is found at high frequencies. Long-range haplotype tests provide evidence of selection for the blue-eye allele at the three haplotyped systems but not for the green/hazel eye SNP allele. We also saw evidence of selection at the derived allele of rs1800414 in East Asia. Our data suggest that the haplotype restricted to Europe is the strongest marker for blue eyes globally and add further inferential evidence that the derived allele of rs1800414 is an East Asian skin pigmentation allele