A nearby long gamma-ray burst from a merger of compact objects.

Gamma-ray bursts (GRBs) are flashes of high-energy radiation arising from energetic cosmic explosions. Bursts of long (greater than two seconds) duration are produced by the core-collapse of massive stars1, and those of short (less than two seconds) duration by the merger of compact objects, such as two neutron stars2. A third class of events with hybrid high-energy properties was identified3, but never conclusively linked to a stellar progenitor. The lack of bright supernovae rules out typical core-collapse explosions4-6, but their distance scales prevent sensitive searches for direct signatures of a progenitor system. Only tentative evidence for a kilonova has been presented7,8. Here we report observations of the exceptionally bright GRB 211211A, which classify it as a hybrid event and constrain its distance scale to only 346 megaparsecs. Our measurements indicate that its lower-energy (from ultraviolet to near-infrared) counterpart is powered by a luminous (approximately 1042 erg per second) kilonova possibly formed in the ejecta of a compact object merger.

Genomic SEM applied to explore etiological divergences in bipolar subtypes.

BACKGROUND: Bipolar disorder (BD) is an overarching diagnostic class defined by the presence of at least one prior manic episode (BD I) or both a prior hypomanic episode and a prior depressive episode (BD II). Traditionally, BD II has been conceptualized as a less severe presentation of BD I, however, extant literature to investigate this claim has been mixed. METHODS: We apply genomic structural equation modeling (Genomic SEM) to investigate divergent genetic pathways across BD's two major subtypes using the most recent GWAS summary statistics from the PGC. We begin by identifying divergences in genetic correlations across 98 external traits using a Bonferroni-corrected threshold. We also use a theoretically informed follow-up model to examine the extent to which the genetic variance in each subtype is explained by schizophrenia and major depression. Lastly, transcriptome-wide SEM (T-SEM) was used to identify neuronal gene expression patterns associated with BD subtypes. RESULTS: BD II was characterized by significantly larger genetic overlap across non-psychiatric medical and internalizing traits (e.g. heart disease, neuroticism, insomnia), while stronger associations for BD I were absent. Consistent with these findings, follow-up modeling revealed a substantial major depression component for BD II. T-SEM results revealed 35 unique genes associated with shared risk across BD subtypes. CONCLUSIONS: Divergent patterns of genetic relationships across external traits provide support for the distinction of the bipolar subtypes. However, our results also challenge the illness severity conceptualization of BD given stronger genetic overlap across BD II and a range of clinically relevant traits and disorders.

The Relationship Between Autonomic Dysfunction and Mood Symptoms in De Novo Parkinson's Disease Patients Over Time.

BACKGROUND: Autonomic dysfunction is prevalent in Parkinson's disease (PD) and can worsen quality of life. We examined: (a) whether specific autonomic symptoms were more strongly associated with anxiety or depression in PD and (b) whether overall autonomic dysfunction predicted mood trajectories over a 5-year period. METHODS: Newly diagnosed individuals with PD (N = 414) from the Parkinson's Progression Markers Initiative completed self-report measures of depression, anxiety, and autonomic symptoms annually. Cross-sectional linear regressions examined relationships between specific autonomic subdomains (gastrointestinal, cardiovascular, thermoregulatory, etc.) and mood. Multilevel modeling examined longitudinal relationships with total autonomic load. RESULTS: Gastrointestinal symptoms were associated with both higher anxiety (b = 1.04, 95% CI [.55, 1.53], P < .001) and depression (b = .24, 95% CI [.11, .37], P = .012), as were thermoregulatory symptoms (anxiety: b = 1.06, 95% CI [.46, 1.65], P = .004; depression: b = .25, 95% CI [.09, .42], P = .013), while cardiovascular (b = .36, 95% CI [.10, .62], P = .012) and urinary symptoms (b = .10, 95% CI [.01, .20], P = .037) were associated only with depression. Longitudinally, higher total autonomic load was associated with increases in both depression (b = .01, 95% CI [.00, .02], P = .015) and anxiety (b = .04, 95% CI [.01, .06], P < .001) over time, as well as occasion-to-occasion fluctuations (depression: b = .08, 95% CI [.05, .10], P < .001; anxiety: b = .24, 95% CI [.15, .32], P < .001). CONCLUSION: Findings suggest autonomic dysfunction, particularly gastrointestinal and thermoregulatory symptoms, may be an indicator for elevated anxiety/depression and a potential treatment target early on in PD.

Greater Apathy Associated With Selective Serotonin Reuptake Inhibitor Use in Parkinson's Disease.

OBJECTIVE: Apathy, a motivational disorder, is common in Parkinson's disease (PD) and often misdiagnosed as depression. Use of selective serotonin reuptake inhibitors (SSRIs) has been associated with increased apathy in adolescents and adults with depression. Based on observations that serotonin may downregulate dopaminergic systems, we examined the relationship between apathy and SSRI use in individuals with PD. METHODS: Medications, mood/motivation scales, and clinical data were collected from a convenience sample of 400 individuals with PD. Depression and apathy were measured using the Beck Depression Inventory-II (BDI-Il) and the Apathy Scale (AS). Antidepressant medications were grouped by mechanism type. RESULTS: Of the 400 PD patients, 26% were on SSRIs. On standard mood/motivation scales, 38% of the sample exceeded clinical cut-offs for apathy and 28% for depression. Results of hierarchical regression analyses revealed that SSRIs were the only antidepressant that were significantly associated with higher apathy scores (ß = .1, P = .02). Less education (ß = -.1, P = .01) worse cognition (ß = -.1, P = .01), and greater depressive symptoms (ß = .5, P < .001) were also significant predictors of apathy. CONCLUSION: These findings suggest that use of SSRIs, but not other antidepressants, is associated with greater apathy in PD. Given the interactive relationship between serotonin and dopamine, the current findings highlight the importance of considering apathy when determining which antidepressants to prescribe to individuals with PD. Similarly, switching a SSRI for an alternative antidepressant in individuals with PD who are apathetic may be a potential treatment for apathy that needs further study.

Liquid Chromatography-Mass Spectrometry Analysis of Frataxin Proteoforms in Whole Blood as Biomarkers of the Genetic Disease Friedreich's Ataxia.

Friedreich's ataxia (FRDA) is caused primarily by expanded GAA repeats in intron 1 of both alleles of the FXN gene, which causes transcriptional silencing and reduced expression of frataxin mRNA and protein. FRDA is characterized by slowly progressive ataxia and cardiomyopathy. Symptoms generally appear during adolescence, and patients slowly progress to wheelchair dependency usually in the late teens or early twenties with death on average in the 4th decade. There are two known mature proteoforms of frataxin. Mitochondrial frataxin (frataxin-M) is a 130-amino acid protein with a molecular weight of 14,268 Da, and there is an alternatively spliced N-terminally acetylated 135-amino acid form (frataxin-E) with a molecular weight of 14,953 Da found in erythrocytes. There is reduced expression of frataxin in the heart and brain, but frataxin is not secreted into the systemic circulation, so it cannot be analyzed in serum or plasma. Blood is a readily accessible biofluid that contains numerous different cell types that express frataxin. We have found that pig blood can serve as an excellent surrogate matrix to validate an assay for frataxin proteoforms because pig frataxin is lost during the immunoprecipitation step used to isolate human frataxin. Frataxin-M is expressed in blood cells that contain mitochondria, whereas extra-mitochondrial frataxin-E is found in erythrocytes. This means that the analysis of frataxin in whole blood provides information on the concentration of both proteoforms without having to isolate the individual cell types. In the current study, we observed that the distributions of frataxin levels for a sample of 25 healthy controls and 50 FRDA patients were completely separated from each other, suggesting 100% specificity and 100% sensitivity for distinguishing healthy controls from FRDA cases, a very unusual finding for a biomarker assay. Additionally, frataxin levels were significantly correlated with the GAA repeat length and age of onset with higher correlations for extra-mitochondrial frataxin-E than those for mitochondrial frataxin-M. These findings auger well for using frataxin levels measured by the validated stable isotope dilution ultrahigh-performance liquid chromatography-multiple reaction monitoring/mass spectrometry assay to monitor therapeutic interventions and the natural history of FRDA. Our study also illustrates the utility of using whole blood for protein disease biomarker discovery and validation.

Temporal Trends and Factors Associated with Receipt of Post-mastectomy Radiation After Neoadjuvant Chemotherapy in Women with cT3 Breast Cancer.

INTRODUCTION: Given the potential impact of increasingly effective neoadjuvant chemotherapy (NACT) on post-mastectomy radiotherapy (PMRT) recommendations, we examined temporal trends in post-NACT PMRT for cT3 breast cancer. METHODS: We identified women ≥ 18 years in the National Cancer Database (NCDB) diagnosed 2004-2019 with cT3N0-1M0 breast cancer treated with chemotherapy and mastectomy. Multivariable logistic regression and Cox proportional hazards models were used to estimate associations between pathologic NACT response [complete response (CR), partial response (PR), or no response (NR); or disease progression (DP)] and PMRT and between PMRT and overall survival (OS), respectively. RESULTS: We identified 39,901 women (Asian/Pacific Islander 1731, Black 5875, Hispanic 3265, White 27,303). Among cN0 patients with CR, PMRT rates declined from 67% in 2004 to 35% in 2019 but remained unchanged for patients with DP. Relative to NR, CR [odds ratio (OR) 0.36, 95% confidence interval (CI) 0.29-0.46] and PR (OR 0.44, 95% CI 0.36-0.55) in cN0 patients were associated with lower odds of PMRT while DP (OR 1.33, 95% CI 1.05-1.69) was associated with higher odds. Among cN1 patients, PMRT rates decreased from 90% to 73% for CR between 2005 and 2019 and increased from 76% to 82% for DP between 2004 and 2019. Relative to NR, CR (OR 0.78, 95% CI 0.63-0.95) was associated with lower odds of PMRT while DP (OR 1.93, 95% CI 1.58-2.37) was associated with higher odds. PMRT was associated with improved OS among cN1 patients (hazard ratio (HR) 0.77, 95% CI 0.67-0.88). CONCLUSION: CR was associated with decreased PMRT receipt over time, while temporal trends following PR and DP differed by cN status, suggesting that nodal involvement guided PMRT receipt more than in-breast disease.

Persisting Effects in Daphnia magna Following an Acute Exposure to Flowback and Produced Waters from the Montney Formation.

Hydraulic fracturing extracts oil and gas through the injection of water and proppants into subterranean formations. These injected fluids mix with the host rock formation and return to the surface as a complex wastewater containing salts, metals, and organic compounds, termed flowback and produced water (FPW). Previous research indicates that FPW is toxic to Daphnia magna (D. magna), impairing reproduction, molting, and maturation time; however, recovery from FPW has not been extensively studied. Species unable to recover have drastic impacts on populations on the ecological scale; thus, this study sought to understand if recovery from an acute 48 h FPW exposure was possible in the freshwater invertebrate, D. magna by using a combination of physiological and molecular analyses. FPW (0.75%) reduced reproduction by 30% and survivorship to 32% compared to controls. System-level quantitative proteomic analyses demonstrate extensive perturbation of metabolism and protein transport in both 0.25 and 0.75% FPW treatments after a 48 h FPW exposure. Collectively, our data indicate that D. magna are unable to recover from acute 48 h exposures to ≥0.25% FPW, as evidence of toxicity persists for at least 19 days post-exposure. This study highlights the importance of considering persisting effects following FPW remediation when modeling potential spill scenarios.

Mechanisms for bacterial gliding motility on soft substrates.

The motility mechanism of certain prokaryotes has long been a mystery, since their motion, known as gliding, involves no external appendages. The physical principles behind gliding still remain poorly understood. Using myxobacteria as an example of such organisms, we identify here the physical principles behind gliding motility and develop a theoretical model that predicts a 2-regime behavior of the gliding speed as a function of the substrate stiffness. Our theory describes the elasto-capillary-hydrodynamic interactions between the membrane of the bacteria, the slime it secretes, and the soft substrate underneath. Defining gliding as the horizontal translation under zero net force, we find the 2-regime behavior is due to 2 distinct mechanisms of motility thrust. On mildly soft substrates, the thrust arises from bacterial shape deformations creating a flow of slime that exerts a pressure along the bacterial length. This pressure in conjunction with the bacterial shape provides the necessary thrust for propulsion. On very soft substrates, however, we show that capillary effects must be considered that lead to the formation of a ridge at the slime-substrate-air interface, thereby creating a thrust in the form of a localized pressure gradient at the bacterial leading edge. To test our theory, we perform experiments with isolated cells on agar substrates of varying stiffness and find the measured gliding speeds in good agreement with the predictions from our elasto-capillary-hydrodynamic model. The mechanisms reported here serve as an important step toward an accurate theory of friction and substrate-mediated interactions between bacteria proliferating in soft media.

Patient evaluation of a virtual visit program for adults with congenital heart disease.

BACKGROUND: Improved longevity for adults with congenital heart disease (ACHD) necessitates regular, longitudinal care for this population. Telemedicine has emerged as a strategy to increase access to subspecialty care. We evaluated patient experience with a virtual visit program in the pre-COVID era to identify patient-centered benefits and limitations. METHODS: We enrolled patients for 30-minute synchronous videoconferencing virtual visits at our institution between October 2013 and March 2019. All patients were Massachusetts residents. Patients were surveyed and their characteristics were abstracted from electronic medical records. RESULTS: A total of 264 virtual visits were conducted among 174 patients with a median age of 40 years. Patients traveled a median of 70 miles for in-person visits. Many visits were to review patient data (47%), and most individuals had moderate complexity CHD (45%). Patients reported very high satisfaction with a median visit rating of 10. Patients mostly preferred virtual visits when considering convenience and cost. No difference in preference to in-person visits was reported when considering sharing private information, confidence that concerns would be addressed, and overall visit quality. In-person visits were still preferred for personal connections and showing a physical problem. CONCLUSION: We find that patients are highly satisfied with virtual visits. ACHD programs should consider blended virtual and in-person care. Long-term regulatory provisions will further improve care through the expansion of telemedicine in the post-COVID era.

Increased mucosal neutrophil survival is associated with altered microbiota in HIV infection.

Gastrointestinal (GI) mucosal dysfunction predicts and likely contributes to non-infectious comorbidities and mortality in HIV infection and persists despite antiretroviral therapy. However, the mechanisms underlying this dysfunction remain incompletely understood. Neutrophils are important for containment of pathogens but can also contribute to tissue damage due to their release of reactive oxygen species and other potentially harmful effector molecules. Here we used a flow cytometry approach to investigate increased neutrophil lifespan as a mechanism for GI neutrophil accumulation in chronic, treated HIV infection and a potential role for gastrointestinal dysbiosis. We report that increased neutrophil survival contributes to neutrophil accumulation in colorectal biopsy tissue, thus implicating neutrophil lifespan as a new therapeutic target for mucosal inflammation in HIV infection. Additionally, we characterized the intestinal microbiome of colorectal biopsies using 16S rRNA sequencing. We found that a reduced Lactobacillus: Prevotella ratio associated with neutrophil survival, suggesting that intestinal bacteria may contribute to GI neutrophil accumulation in treated HIV infection. Finally, we provide evidence that Lactobacillus species uniquely decrease neutrophil survival and neutrophil frequency in vitro, which could have important therapeutic implications for reducing neutrophil-driven inflammation in HIV and other chronic inflammatory conditions.

PlpA, a PilZ-like protein, regulates directed motility of the bacterium Myxococcus xanthus.

The rod-shaped bacterium Myxococcus xanthus moves on surfaces along its long cell axis and reverses its moving direction regularly. Current models propose that the asymmetric localization of a Ras-like GTPase, MglA, to leading cell poles determines the moving direction of cells. However, cells are still motile in the mutants where MglA localizes symmetrically, suggesting the existence of additional regulators that control moving direction. In this study, we identified PlpA, a PilZ-like protein that regulates the direction of motility. PlpA and MglA localize into opposite asymmetric patterns. Deletion of the plpA gene abolishes the asymmetry of MglA localization, increases the frequency of cellular reversals and leads to severe defects in cell motility. By tracking the movements of single motor particles, we demonstrated that PlpA and MglA co-regulated the direction of gliding motility through direct interactions with the gliding motor. PlpA inhibits the reversal of individual gliding motors while MglA promotes motor reversal. By counteracting MglA near lagging cell poles, PlpA reinforces the polarity axis of MglA and thus stabilizes the direction of motility.

Trends in transcatheter and operative closure of patent ductus arteriosus in neonatal intensive care units: Analysis of data from the Pediatric Health Information Systems Database.

BACKGROUND: The risks and benefits of pharmacologic treatment and operative closure of patent ductus arteriosus (O-PDA) in premature infants remain controversial. Recent series have demonstrated the feasibility of transcatheter PDA closure (TC-PDA) in increasingly small infants. The effect of this change on practice has not been evaluated. METHODS: A multicenter observational study of infants treated in neonatal intensive care units in hospitals contributing data to the Pediatric Health Information Systems Database from January 2007 to December 2017 was performed to study trends in the propensities for (1) mechanical closure of PDA and (2) TC-PDA versus O-PDA, as well as interhospital variation in practice. RESULTS: A total of 6,214 subjects at 44 hospitals were studied (5% TC-PDA). Subject median gestational age was 25 weeks (interquartile range: 24-27 weeks). Median age at closure was 24 days (interquartile range: 14-36 days). The proportion of all neonatal intensive care unit patients undergoing either O-PDA or TC-PDA decreased (3.1% in 2007 and 0.7% in 2017, P < .001), whereas the proportion in which TC-PDA was used increased significantly (0.1% in 2007 to 29.0% in 2017). Case-mix-adjusted multivariable models similarly demonstrated increasing propensity to pursue TC-PDA (odds ratio [OR] 1.66 per year, P < .001) with acceleration of the trend after 2014 (OR 2.46 per year, P < .001) as well as significant practice variation (P < .001, median OR 4.6) across the study period. CONCLUSIONS: In the face of decreasing closure of PDA, the use of TC-PDA increased dramatically with significant practice variability. This demonstrates that there is equipoise for potential clinical trials.

Occurrence and determinants of Klebsiella species bloodstream infection in the western interior of British Columbia, Canada.

BACKGROUND: Klebsiella species are among the most common causes of bloodstream infection (BSI). However, few studies have evaluated their epidemiology in non-selected populations. The objective was to define the incidence of, risk factors for, and outcomes from Klebsiella species BSI among residents of the western interior of British Columbia, Canada. METHODS: Population-based surveillance was conducted between April 1, 2010 and March 31, 2017. RESULTS: 151 episodes were identified for an incidence of 12.1 per 100,000 population per year; the incidences of K. pneumoniae and K. oxytoca were 9.1 and 2.9 per 100,000 per year, respectively. Overall 24 (16%) were hospital-onset, 90 (60%) were healthcare-associated, and 37 (25%) were community-associated. The median patient age was 71.4 (interquartile range, 58.8-80.9) years and 88 (58%) cases were males. Episodes were uncommon among patients aged < 40 years old and no cases were observed among those aged < 10 years. A number of co-morbid medical illnesses were identified as significant risks and included (incidence rate ratio; 95% confidence interval) cerebrovascular accident (5.9; 3.3-9.9), renal disease 4.3; 2.5-7.0), cancer (3.8; 2.6-5.5), congestive heart failure (3.5; 1.6-6.6), dementia (2.9; 1.5-5.2), diabetes mellitus (2.6; 1.7-3.9), and chronic obstructive pulmonary disease (2.3; 1.5-3.5). Of the 141 (93%) patients admitted to hospital, the median hospital length stay was 8 days (interquartile range, 4-17). The in-hospital and 30-day all cause case-fatality rates were 24/141 (17%) and 27/151 (18%), respectively. CONCLUSIONS: Klebsiella species BSI is associated with a significant burden of illness particularly among those with chronic co-morbid illnesses.

Clinical utility of portable electrophysiology to measure fatigue in treatment-naïve non-small cell lung cancer.

PURPOSE: Cancer-related fatigue (CRF) biology remains poorly understood. Responsible mechanisms may be central or peripheral and originate anywhere from the brain to muscle fiber. Objective measurement is complex and previously limited to specialized laboratories. Portable electroencephalography (EEG) and electromyography (EMG) may enhance objective measurement. This study evaluated the feasibility and acceptability of portable EMG-EEG in CRF assessment. METHODS: A prospective observational feasibility study compared ten outpatients with inoperable, treatment-naïve non-small cell lung cancer and CRF to ten healthy volunteers. All completed a sustained isometric hand-grip contraction at 30% maximal level until self-perceived exhaustion. 128-channel EEG and 2-channel EMG signals of forearm muscles were recorded. Device acceptability was evaluated by questionnaire. RESULTS: The task was evaluated in two stages; first and last 20 s. CRF cohort perceived exhaustion earlier than volunteers (mean 137 ± 76 s vs 208 ± 51 s). As fatigue progressed, EMG amplitude increased significantly (CRF p = 0.02; volunteers: p = 0.04) in both groups as did EMG beta band power (CRF p = 0.008; volunteers: p = 0.006). The increase was significantly less in CRF (amplitude p = 0.032; beta power: p = 0.014). EEG beta band power in the contralateral motor cortex increased significantly (CRF p = 0.03; volunteers: p = 0.019) in both cohorts but to greater extent (p = 0.024) in CRF. One hundred percent device acceptability was reported. CONCLUSIONS: A laboratory-based evaluation was successfully adapted to the outpatient setting during routine visits. High acceptability supports clinical utility. In CRF, a higher degree of cortical activation was required to drive a much lower level of muscle performance. This suggests impairment of both central and peripheral mechanisms in CRF.

The pathophysiology of cancer-related fatigue: current controversies.

Fatigue is one of the most common and debilitating cancer symptoms, and is associated with impaired quality of life. The exact pathophysiology of cancer-related fatigue (CRF) is poorly understood, but in any individual, it is likely multifactorial and involves inter-related cytokine, muscular, neurotransmitter, and neuroendocrine changes. Underlying CRF mechanisms proposed include central and peripheral hypotheses. Central mechanisms include hypotheses about cytokine dysregulation, hypothalamic-pituitary-adrenal-axis disruption, circadian rhythm disruption, serotonin, and vagal afferent nerve function while peripheral mechanisms include hypotheses about adenosine triphosphate and muscle contractile properties. Currently, these hypotheses are largely based on evidence from other conditions in which fatigue is characteristic. The purpose of this article is to provide a narrative review of the literature and present the current controversies in the pathophysiology of CRF, particularly in relation to central and peripheral hypotheses for CRF. An understanding of pathophysiology may facilitate direct and simple therapeutic interventions for those with cancer.

Influence of specific surface area on coal dust explosibility using the 20-L chamber.

The relationship between the explosion inerting effectiveness of rock dusts on coal dusts, as a function of the specific surface area (cm2/g) of each component is examined through the use of 20-L explosion chamber testing. More specifically, a linear relationship is demonstrated for the rock dust to coal dust (or incombustible to combustible) content of such inerted mixtures with the specific surface area of the coal and the inverse of that area of the rock dust. Hence, the inerting effectiveness, defined as above, is more generally linearly dependent on the ratio of the two surface areas. The focus on specific surface areas, particularly of the rock dust, provide supporting data for minimum surface area requirements in addition to the 70% less than 200 mesh requirement specified in 30 CFR 75.2.

4n-1 Is a "Sweet Spot" in DNA i-Motif Folding of 2'-Deoxycytidine Homopolymers.

Strands of DNA with four or more contiguous runs of 2'-deoxycytidine (dC) nucleotides have the potential to adopt i-motif folds, generally under mildly acidic conditions. Analysis of dC homo-oligonucleotide strands ranging in length from 10 to 30 nucleotides by five different pH-dependent methods identified a pattern in strand length vs stability. Beginning with dC11, which does not fold, the transition pH (pHT) increased with chain length with the addition of up to four nucleotides, after which the stability dramatically decreased, and the trend repeated this cycle up to dC27. The analysis found dCn strands of length 15, 19, 23, and 27 nucleotides (i.e., 4n-1) to have pHT values >7.2 and thermal stabilities >37 °C at pH 7.0. Model studies using thymidine nucleotides to lock in i-motif loop lengths support the conclusion that the most stable dCn i-motifs possess one nucleotide in each of the three loops and a core built of an even number of base pairs. The pattern identified from the model studies occurs with a frequency of four nucleotides at lengths of 15, 19, 23, and 27 in accordance with the results obtained for the dCn strands. This observation led us to interrogate the human genome for dCn runs. Inspection of the human genome indicates that dCn runs are enriched in critical regions of the genome (promoters, UTRs, and introns), while being depleted in coding and intergenic regions, and these findings may have biological implications. Lastly, the ability to tune i-motif stabilities by the length of the strand might be harnessed for stimulus-responsive applications in DNA scaffolds, sensors, nanotechnology, and other chemical applications.

Subjective and objective taste and smell changes in cancer.

CONTEXT: Malnutrition is highly prevalent in cancer patients and an important predictor of morbidity, mortality, treatment response, and toxicity. Taste and smell changes (TSCs) are common and may contribute to malnutrition. Research has previously focused on patients receiving chemotherapy (CT) or head and neck radiotherapy (RT). However, TSCs may occur pre-treatment, with other treatment modalities, and in cancer survivors. This review evaluates objective and subjective assessment of taste and smell, discusses the prevalence of TSCs in cancer, and reviews the clinical sequelae of TSCs in cancer patients. OBJECTIVES: To critically evaluate objective and subjective assessment of TSCs, and the prevalence and clinical sequelae of TSCs in cancer. METHODS: A literature search was conducted using PubMed, CINAHL and Embase for English-language articles published January 2009-June 2016. Search terms included combinations of the following: chemosensory, taste, smell, cancer, chemotherapy, radiotherapy, hormone therapy, immunotherapy, survivors. Reference lists of articles retrieved were also reviewed. RESULTS: Variation in objective and subjective assessment methodologies has resulted in difficulties interpreting the literature. TSC prevalence varies depending on stage of disease and treatment regimens, from 16% to 70% and 50% to 70% during CT and RT, respectively. TSCs in patients who are treatment-naïve, receiving hormone or immunotherapy treatment, post-treatment and cancer survivors have not been adequately studied. TSCs are associated with impaired nutritional status. The relationship between cancer-associated symptoms and nutritional status is not clearly defined. CONCLUSION: There is no gold standard assessment tool for TSCs. Heterogeneity in study methods hinders conclusive identification of the most appropriate way to measure TSCs. Subjective measures may reflect the patient experience and more reliably predict changes in dietary behaviour. Evaluation of TSCs should form part of all nutritional assessments in cancer patients. The true prevalence and severity of TSCs at all stages of cancer could then be established.

Intrinsic coincident full-Stokes polarimeter using stacked organic photovoltaics.

An intrinsic coincident full-Stokes polarimeter is demonstrated by using strain-aligned polymer-based organic photovoltaics (OPVs) that can preferentially absorb certain polarized states of incident light. The photovoltaic-based polarimeter is capable of measuring four Stokes parameters by cascading four semitransparent OPVs in series along the same optical axis. This in-line polarimeter concept potentially ensures high temporal and spatial resolution with higher radiometric efficiency as compared to the existing polarimeter architecture. Two wave plates were incorporated into the system to modulate the S3 Stokes parameter so as to reduce the condition number of the measurement matrix and maximize the measured signal-to-noise ratio. Radiometric calibration was carried out to determine the measurement matrix. The polarimeter presented in this paper demonstrated an average RMS error of 0.84% for reconstructed Stokes vectors after normalized to S0. A theoretical analysis of the minimum condition number of the four-cell OPV design showed that for individually optimized OPV cells, a condition number of 2.4 is possible.