Multichannel Doppler fiber-imager spectrometer for spatiotemporal characterization of high-intensity laser-driven plasmas.

We demonstrate a flexible multichannel fiber-based imaging Doppler spectrometer to characterize plasmas in high intensity (≥1 × 1018 W/cm2) laser-plasma experiments at high repetition rates. This instrument collects data from ×21 different plasma locations combining optical fibers and a single imaging spectrometer. This diagnostic maps the plasma velocity evolution as a function of time with sub-pico-second resolution. Experimental results showing 2D velocity measurements of plasma with 20 µm spatial resolution are presented. Intensities of the order of 1018 W/cm2 were used to generate a plasma, while a much less intense, frequency doubled (400 nm), probe beam (1011 W/cm2) was used to measure the Doppler shift from the plasma critical surface. The instrument can be scaled to a larger number of channels (e.g., 100) still using a single spectrometer.

Evaluation of 278 New Bluephase Style Light Curing Units Purchased Over Six Years.

OBJECTIVE: This study measured 278 new curing lights (LCUs) to determine if they met the manufacturer's specifications. MATERIALS AND METHODS: Over a 6-year period, the light output from 278 Bluephase Style LCUs was measured before the LCUs were given to students (41 in 2017, 44 in 2018, 46 in 2019, 48 in 2020, 50 in 2021, and 49 in 2022). The radiant exitance (mW/cm²) from each year was compared using ANOVA and Tukey- Kramer multiple comparisons test with adjustment for the unequal sample sizes (α=0.05). The results were also compared against the manufacturer's stated radiant exitance of 1200 mW/cm². RESULTS: The 278 LCUs delivered an average (± standard deviation) radiant exitance of 1203 ± 16.7 mW/cm². The lowest radiant exitance was 1149 mW/cm² and the highest was 1257 mW/cm². Although there were statistically significant differences in the LCUs from each year, these values were within the manufacturer's tolerance of values of ± 10%. Approximately 13% of the emitted light was below 420 nm, and 87% was above 420 nm. CONCLUSION: These new LCUs were all multiple peak LCUs that emitted an average radiant exitance of 1,203 mW/cm² (range 1149 to 1257 mW/cm². Purchasers of the Style LCU can be confident that their new LCU will meet the manufacturer's specifications.

Flexible tape-drive target system for secondary high-intensity laser-driven sources.

We present the development of a flexible tape-drive target system to generate and control secondary high-intensity laser-plasma sources. Its adjustable design permits the generation of relativistic MeV particles and x rays at high-intensity (i.e., ≥1 × 1018 W cm-2) laser facilities, at high repetition rates (>1 Hz). The compact and robust structure shows good mechanical stability and a high target placement accuracy (<4 µm RMS). Its compact and flexible design allows for mounting in both the horizontal and vertical planes, which makes it practical for use in cluttered laser-plasma experimental setups. The design permits ∼170° of access on the laser-driver side and 120° of diagnostic access at the rear. A range of adapted apertures have been designed and tested to be easily implemented to the targetry system. The design and performance testing of the tape-drive system in the context of two experiments performed at the COMET laser facility at the Lawrence Livermore National Laboratory and at the Advanced Lasers and Extreme Photonics (ALEPH) facility at Colorado State University are discussed. Experimental data showing that the designed prototype is also able to both generate and focus high-intensity laser-driven protons at high repetition rates are also presented.

A flexible proton beam imaging energy spectrometer (PROBIES) for high repetition rate or single-shot high energy density (HED) experiments (invited).

The PROBIES diagnostic is a new, highly flexible, imaging and energy spectrometer designed for laser-accelerated protons. The diagnostic can detect low-mode spatial variations in the proton beam profile while resolving multiple energies on a single detector or more. When a radiochromic film stack is employed for "single-shot mode," the energy resolution of the stack can be greatly increased while reducing the need for large numbers of films; for example, a recently deployed version allowed for 180 unique energy measurements spanning ∼3 to 75 MeV with <0.4 MeV resolution using just 20 films vs 180 for a comparable traditional film and filter stack. When utilized with a scintillator, the diagnostic can be run in high-rep-rate (>Hz rate) mode to recover nine proton energy bins. We also demonstrate a deep learning-based method to analyze data from synthetic PROBIES images with greater than 95% accuracy on sub-millisecond timescales and retrained with experimental data to analyze real-world images on sub-millisecond time-scales with comparable accuracy.

Self-reported gastrointestinal disorders among veterans with gulf war illness with and without posttraumatic stress disorder.

BACKGROUND: Gulf War Illness (GWI) is a chronic, multi-symptom disorder affecting 25%-32% of Gulf War veterans. Veterans with GWI disproportionately suffer from gastrointestinal (GI) disorders. Given the increasing evidence supporting a gut-brain axis, we explore the relationship between post-traumatic stress disorder (PTSD), GWI, and self-reported GI disorders among GW veterans. METHODS: Veterans from the Gulf War Era Cohort and Biorepository responded to a mail-based survey (N = 1058). They were stratified by GWI (Centers for Disease Control definition) and PTSD status. This yielded three groups: GWI-, GWI+/PTSD-, and GWI+/PTSD+. Multivariable logistic regression adjusting for demographic and military characteristics examined associations between GWI/PTSD groups and GI disorders. Results were expressed as adjusted odds ratios (aOR) with 95% confidence intervals (95% CI). KEY RESULTS: The most frequently reported GI disorders were irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD), and colon polyps (CP). The GWI+/PTSD+ group had a higher odds of these disorders than the GWI+/PTSD- group (aORIBS  = 3.12, 95% CI: 1.93-5.05; aORGERD  = 2.04, 95% CI: 1.44-2.90; aORCP  = 1.85, 95% CI: 1.23-2.80), which had a higher odds of these disorders than the GWI- group (aORIBS  = 4.38, 95% CI: 1.55-12.36; aORGERD  = 2.51 95% CI: 1.63-3.87; aORCP  = 2.57, 95% CI: 1.53-4.32). CONCLUSIONS & INFERENCES: GW veterans with GWI and PTSD have significantly higher odds of specific self-reported GI disorders than the other groups. Given the known bidirectional influences of the gut and brain, these veterans may benefit from a holistic healthcare approach that considers biopsychosocial contributors to the assessment and management of disease.

Biopolymer Non-Parametric Analysis: A Degradation Study under Accelerated Destructive Tests.

The degradation of biopolymers such as polylactic acid (PLA) has been studied for several years; however, the results regarding the mechanism of degradation are not completely understood yet. PLA is easily processed by traditional techniques including injection molding, blow molding, extrusion, and thermoforming; in this research, the extrusion and injection molding processes were used to produce PLA samples for accelerated destructive testing. The methodology employed consisted of carrying out material testing under the guidelines of several ASTM standards; this research hypothesized that the effects of UV light, humidity, and temperature exposure have a statistical difference in the PLA degradation rate. The multivariate analysis of non-parametric data is presented as an alternative to multivariate analysis, in which the data do not satisfy the essential assumptions of a regular MANOVA, such as multivariate normality. A package in the R software that allows the user to perform a non-parametric multivariate analysis when necessary was used. This paper presents a study to determine if there is a significant difference in the degradation rate after 2000 h of accelerated degradation of a biopolymer using the multivariate and non-parametric analyses of variance. The combination of the statistical techniques, multivariate analysis of variance and repeated measures, provided information for a better understanding of the degradation path of the biopolymer.

Applications of machine learning to a compact magnetic spectrometer for high repetition rate, laser-driven particle acceleration.

Accurately and rapidly diagnosing laser-plasma interactions is often difficult due to the time-intensive nature of the analysis and will only become more so with the rise of high repetition rate lasers and the desire to implement feedback on a commensurate timescale. Diagnostic analysis employing machine learning techniques can help address this problem while maintaining a high degree of accuracy. We report on the application of machine learning to the analysis of a scintillator-based electron spectrometer for experiments on high intensity, laser-plasma interactions at the Colorado State University Advanced Lasers and Extreme Photonics facility. Our approach utilizes a neural network trained on synthetic data and tested on experiments to extract the accelerated electron temperature. By leveraging transfer learning, we demonstrate an improvement in the neural network accuracy, decreasing the network error by 50%.

Enabling uptake and sustainability of supervision roles by women GPs in Australia: a narrative analysis of interviews.

BACKGROUND: Worldwide, the proportion of women entering careers in medicine is increasing. To ensure diversity and capacity in the general practice ("GP") supervision workforce, a greater understanding from the perspective of women GPs engaged in or considering the clinical supervision of trainee doctors is important. This narrative inquiry aims to explore the uptake and sustainability of supervision roles for women GPs in the Australian context. METHODS: Qualitative interviews with Australian women GPs were conducted between July and September 2021. Women GPs were selected to represent a range of demographics, practice contexts, and supervision experience to promote broad perspectives. Narrative analysis drew on participant perspectives, allowing emergent stories to be explored using story arcs based on the characters, settings, problems, actions, and resolutions. These stories were evaluated by a broad research team and a high level of agreement of the final narratives and counter-narratives was achieved. RESULTS: Of the 25 women who enrolled, 17 completed interviews. Six narratives emerged, including: power and control, pay, time, other life commitments, quality of supervision, and supervisor identity. These represented significant intersecting issues with the potential to impact the uptake and sustainability of supervision by women GPs. Some women GPs reported a lack of agency to make decisions about their role in supervision and were not remunerated for teaching. Uptake and sustainability of supervision was constrained by other life commitments, which could be buffered by team-sharing arrangements and a supportive practice. Although adding a burden of time atop their complex and sensitive consultations, women GPs were committed to being available to registrars and supervising at a high standard. To foster high quality supervision, women GPs were interested in up-skilling resources, building experience and harnessing support networks. Women sensed imposter syndrome when negotiating a supervisor identity, which could be managed by explicitly valuing their contribution. CONCLUSION: The findings can inform the development of more specific resources, supports and structures to enable women GPs in Australia to uptake and sustain the supervision of trainee doctors at a level they find both acceptable and rewarding.

Use of the Portsmouth Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity ('P-POSSUM') to predict morbidity in patients undergoing surgery with reconstruction for temporal bone malignancy.

OBJECTIVE: The Portsmouth Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity ('P-POSSUM') is a two-part scoring system that includes a physiological assessment and a measure of operative severity. This study sought to determine whether risk estimates for this scoring system could be used in major head and neck reconstructive surgery. METHOD: A retrospective review was performed of patients undergoing resection for a temporal bone malignancy in a single head and neck centre in Dublin, Ireland, from 2002 to 2021. RESULTS: The mean ± standard deviation morbidity estimate calculated using the scoring system was 47.6 per cent ± 19.5 per cent. The actual rate of complications was 47 per cent. The optimal cut-off for the scoring system was calculated using the Youden index from the receiver operating characteristic curve, which was 40.5 per cent in this case. CONCLUSION: The study indicates that the Portsmouth Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity is a useful tool for predicting morbidity risk in patients undergoing head and neck resection with reconstruction for temporal bone malignancies.

Achievement of maturational milestones among very low birth weight infants.

BACKGROUND: Very low birth weight (VLBW) infants must achieve several maturational milestones to be discharged home from the NICU. OBJECTIVE: Describe the timing of maturational milestones in VLBW infants and the impact of clinical variables and milestone achievement on postmenstrual age (PMA) at discharge. METHODS: For VLBW infants without severe lung disease discharged home from a level IV NICU, we assessed PMA at the achievement of thermoregulation, cardiorespiratory stability, feeding, and discharge. RESULTS: In 400 infants (median GA 28.4 weeks), lower birth weight, white race, and having multiple comorbidities of prematurity predicted later discharge PMA. The most common milestone sequence was CPAP discontinuation, caffeine discontinuation, thermoregulation, apnea resolution, and full oral feeds. PMA at apnea resolution and full oral feeds correlated highly with discharge PMA. CONCLUSIONS: In a single-center VLBW cohort, comorbidities of prematurity impacted the timing of NICU discharge through delay in oral feeding and cardiorespiratory stability.

Biopolymer Degradation Analysis: Accelerated Life Testing Study to Characterize Polylactic Acid Durability.

While the degradation of Polylactic Acid (PLA) has been studied for several years, results regarding the mechanism for determining degradation are not completely understood. Through accelerated degradation testing, data can be extrapolated and modeled to test parameters such as temperature, voltage, time, and humidity. Accelerated lifetime testing is used as an alternative to experimentation under normal conditions. The methodology to create this model consisted of fabricating series of ASTM specimens using extrusion and injection molding. These specimens were tested through accelerated degradation; tensile and flexural testing were conducted at different points of time. Nonparametric inference tests for multivariate data are presented. The results indicate that the effect of the independent variable or treatment effect (time) is highly significant. This research intends to provide a better understanding of biopolymer degradation. The findings indicated that the proposed statistical models can be used as a tool for characterization of the material regarding the durability of the biopolymer as an engineering material. Having multiple models, one for each individual accelerating variable, allow deciding which parameter is critical in the characterization of the material.

The Potential Impact and Usability of the Eighth Edition TNM Staging Classification in Oral Cavity Cancer.

AIMS: In the current eighth edition head and neck TNM staging, extranodal extension (ENE) is an adverse feature in oral cavity squamous cell cancer (OSCC). The previous seventh edition N1 with ENE is now staged as N2a. Seventh edition N2+ with ENE is staged as N3b in the eighth edition. We evaluated its potential impact on patients treated with surgery and postoperative intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: OSCC patients treated with primary surgery and adjuvant (chemo)radiotherapy between January 2005 and December 2014 were reviewed. Cohorts with pathological node-negative (pN-), pathological node-positive without ENE (pN+_pENE-) and pathological node-positive with ENE (pN+_pENE+) diseases were compared for local control, regional control, distant control and overall survival. The pN+ cohorts were further stratified into seventh edition N-staging subgroups for outcomes comparison. RESULTS: In total, 478 patients were evaluated: 173 pN-; 159 pN+_pENE-; 146 pN+_pENE+. Outcomes at 5 years were: local control was identical (78%) in all cohorts (P = 0.892), whereas regional control was 91%, 80% and 68%, respectively (P < 0.001). Distant control was 97%, 87%, 68% (P < 0.001) and overall survival was 75%, 53% and 39% (P < 0.001), respectively. Overall survival for N1 and N2a subgroups was not significantly different. In the seventh edition N2b subgroup of pENE- (n = 79) and pENE+ (n = 79) cohorts, overall survival was 67% and 37%, respectively. In the seventh edition N2c subgroups, overall survival for pENE- (n = 17) and pENE+ (n = 38) cohorts was 65% and 35% (P = 0.08), respectively. Overall, an additional 128 patients (42% pN+) were upstaged as N3b. CONCLUSIONS: When eighth edition staging was applied, stage migration across the N2-3 categories resulted in expected larger separations of overall survival by stage. Patients treated with primary radiation without surgical staging should have outcomes carefully monitored. Strategies to predict ENE preoperatively and trials to improve the outcomes of pENE+ patients should be explored.

Clinical and vital sign changes associated with late-onset sepsis in very low birth weight infants at 3 NICUs.

BACKGROUND: In premature infants, clinical changes frequently occur due to sepsis or non-infectious conditions, and distinguishing between these is challenging. Baseline risk factors, vital signs, and clinical signs guide decisions to culture and start antibiotics. We sought to compare heart rate (HR) and oxygenation (SpO2) patterns as well as baseline variables and clinical signs prompting sepsis work-ups ultimately determined to be late-onset sepsis (LOS) and sepsis ruled out (SRO). METHODS: At three NICUs, we reviewed records of very low birth weight (VLBW) infants around their first sepsis work-up diagnosed as LOS or SRO. Clinical signs prompting the evaluation were determined from clinician documentation. HR-SpO2 data, when available, were analyzed for mean, standard deviation, skewness, kurtosis, and cross-correlation. We used LASSO and logistic regression to assess variable importance and associations with LOS compared to SRO. RESULTS: We analyzed sepsis work-ups in 408 infants (173 LOS, 235 SRO). Compared to infants with SRO, those with LOS were of lower GA and BW, and more likely to have a central catheter and mechanical ventilation. Clinical signs cited more often in LOS included hypotension, acidosis, abdominal distension, lethargy, oliguria, and abnormal CBC or CRP(p < 0.05). HR-SpO2 data were available in 266 events. Cross-correlation HR-SpO2 before the event was associated with LOS after adjusting for GA, BW, and postnatal age. A model combining baseline, clinical and HR-SpO2 variables had AUC 0.821. CONCLUSION: In VLBW infants at 3-NICUs, we describe the baseline, clinical, and HR-SpO2 variables associated with LOS versus SRO.

A study to assess smoking habits and smoking exposure in sportspeople.

BACKGROUND: Tobacco smoking is a leading public health concern and is the most preventable cause of morbidity and mortality worldwide. Sportspeople are no exception and those who smoke are predisposed to the same hazardous health effects as the general public, in addition to the potential effects it may have on their sporting performance. AIM: We aimed to ascertain the prevalence of tobacco consumption in a sporting population. We also endeavoured to quantify the use of electronic cigarettes (e-cigarettes) and assess exposure to passive smoking. DESIGN: Observational study. METHODS: A web-based e-questionnaire was distributed to participants from various sports across Ireland between November 2017 and January 2018, and data were analysed using SPSS. RESULTS: A total of 546 sportspeople completed the survey with more than twice as many male respondents. Of whom, 16% of participants were current smokers, with males significantly more likely to smoke (P < 0.001), 26% of rugby players were current smokers which was significantly higher when compared with other sports (P < 0.01), 10% of all participants were exposed to second-hand smoke for more than 1 h per day and 2% of all participants were current users of e-cigarettes. CONCLUSION: The prevalence of smoking in our study population was higher than other literature reports. Further studies are essential to evaluate the potential negative effects this may be having on sporting performance, career progression and indeed injury occurrence/rehabilitation. It is imperative to address the matter of smoking in athletes, not only for public health concerns but also considering they are important role models in our society.

Urinary tract infections in very low birthweight infants: A two-center analysis of microbiology, imaging and heart rate characteristics.

BACKGROUND: Increased understanding of characteristics of urinary tract infection (UTI) among very low birthweight infants (VLBW) might lead to improvement in detection and treatment. Continuous monitoring for abnormal heart rate characteristics (HRC) could provide early warning of UTIs. OBJECTIVE: Describe the characteristics of UTI, including HRC, in VLBW infants. METHODS: We reviewed records of VLBW infants admitted from 2005-2010 at two academic centers participating in a randomized clinical trial of HRC monitoring. Results of all urine cultures, renal ultrasounds (RUS), and voiding cystourethrograms (VCUG) were assessed. Change in the HRC index was analyzed before and after UTI. RESULTS: Of 823 VLBW infants (27.7±2.9 weeks GA, 53% male), 378 had > / = 1 urine culture obtained. A UTI (≥10,000 CFU and >five days of antibiotics) was diagnosed in 80 infants, (10% prevalence, mean GA 25.8±2.0 weeks, 76% male). Prophylactic antibiotics were administered to 29 (36%) infants after UTI, of whom four (14%) had another UTI. Recurrent UTI also occurred in 7/51 (14%) of infants not on uroprophylaxis after their first UTI. RUS was performed after UTI in 78%, and hydronephrosis and other major anomalies were found in 19%. A VCUG was performed in 48% of infants and 18% demonstrated vesicoureteral reflux (VUR). The mean HRC rose and fell significantly in the two days before and after diagnosis of UTI. CONCLUSIONS: UTI was diagnosed in 10% of VLBW infants, and the HRC index increased prior to diagnosis, suggesting that continuous HRC monitoring in the NICU might allow earlier diagnosis and treatment of UTI.

MRI Spectrum of Brain Involvement in Sphingosine-1-Phosphate Lyase Insufficiency Syndrome.

SGPL1 encodes sphingosine-1-phosphate lyase, the final enzyme of sphingolipid metabolism. In 2017, a condition featuring steroid-resistant nephrotic syndrome and/or adrenal insufficiency associated with pathogenic SGPL1 variants was reported. In addition to the main features of the disease, patients often exhibit a range of neurologic deficits. In a handful of cases, brain imaging results were described. However, high-quality imaging results and a systematic analysis of brain MR imaging findings associated with the condition are lacking. In this study, MR images from 4 new patients and additional published case reports were reviewed by a pediatric neuroradiologist. Analysis reveals recurring patterns of features in affected patients, including isolated callosal dysgenesis and prominent involvement of the globus pallidus, thalamus, and dentate nucleus, with progressive atrophy and worsening of brain lesions. MR imaging findings of abnormal deep gray nuclei, microcephaly, or callosal dysgenesis in an infant or young child exhibiting other typical clinical features of sphingosine-1-phosphate lyase insufficiency syndrome should trigger prompt genetic testing for SGPL1 mutations.

Phase I trial of alpelisib in combination with concurrent cisplatin-based chemoradiotherapy in patients with locoregionally advanced squamous cell carcinoma of the head and neck.

BACKGROUND: Deregulation of the PI3K signalling pathway is frequent in squamous cell carcinoma of the head and neck (SCCHN) and may be implicated in radioresistance. We report on the results from a phase I 3 + 3 dose escalation study of alpelisib, a class I α-specific PI3K inhibitor in combination with concurrent cisplatin-based chemoradiation (CRT) in patients with locoregionally advanced SCCHN (LA-SCCHN). METHODS: Eligible patients had previously untreated LA-SCCHN and were candidates for CRT. The primary objective was to evaluate safety and determine the recommended phase II dose (RP2D). Alpelisib was given orally once daily at two dose levels: 200 mg and 250 mg. CRT consisted of cisplatin 100 mg/m2 IV every three weeks and standard fractionation radiotherapy (IMRT) 70 Gy in 35 fractions. RESULTS: Nine patients were enrolled (six alpelisib 200 mg, three 250 mg). Oropharynx was the primary site in all patients (seven p16-positive; five T1-2N2M0, four T3-4N2-3M0 [AJCC 7th edition]). All patients completed CRT within seven weeks. Grade 3 alpelisib-related toxicities occurred in four patients. No dose-limiting toxicity (DLT) was observed at 200 mg among three DLT-evaluable patients. Two of two DLT-evaluable patients treated at 250 mg experienced DLTs (inability to complete ≥75% alpelisib secondary to radiation dermatitis and febrile neutropenia). Thus, RP2D was declared at 200 mg. After median follow-up of 39.7 months, two patients developed pulmonary metastases despite locoregional control. Three-year overall survival was 77.8% (95% CI 36.5%-93.9%). CONCLUSION: Alpelisib at 200 mg has a manageable safety profile in combination with cisplatin-based CRT in LA-SCCHN.

Development and validation of a clinical prediction-score model for distant metastases in major salivary gland carcinoma.

BACKGROUND: The most common pattern of failure in major salivary gland carcinoma (SGC) is development of distant metastases (DMs). The objective of this study was to develop and validate a prediction score for DM in SGC. PATIENTS AND METHODS: Patients with SGC treated curatively at four tertiary cancer centers were divided into discovery (n = 619) and validation cohorts (n = 416). Multivariable analysis using competing risk regression was used to identify predictors of DM in the discovery cohort and create a prediction score of DM; the optimal score cut-off was determined using a minimal P value approach. The prediction score was subsequently evaluated in the validation cohort. The cumulative incidence and Kaplan-Meier methods were used to analyze DM and overall survival (OS), respectively. RESULTS: In the discovery cohort, DM predictors (risk coefficient) were: positive margin (0.6), pT3-4 (0.7), pN+ (0.7), lymphovascular invasion (0.8), and high-risk histology (1.2). High DM-risk SGC was defined by sum of coefficients greater than two. In the discovery cohort, the 5-year incidence of DM for high- versus low-risk SGC was 50% versus 8% (P < 0.01); this was similar in the validation cohort (44% versus 4%; P < 0.01). In the pooled cohorts, this model performed similarly in predicting distant-only failure (40% versus 6%, P < 0.01) and late (>2 years post surgery) DM (22% versus 4%; P < 0.01). Patients with high-risk SGC had an increased incidence of DM in the subgroup receiving postoperative radiation therapy (46% versus 8%; P < 0.01). The 5-year OS for high- versus low-risk SGC was 48% versus 92% (P < 0.01). CONCLUSION: This validated prediction-score model may be used to identify SGC patients at increased risk for DM and select those who may benefit from prospective evaluation of treatment intensification and/or surveillance strategies.