Longitudinal changes in home food availability and concurrent associations with food and nutrient intake among children at 24-48 months.

OBJECTIVES: To describe changes in home food availability during early childhood, including modified, developmentally sensitive obesogenic scores, and to determine whether home food availability is associated with food and nutrient intakes of children concurrently, over time. DESIGN: Data were drawn from the STRONG Kids 2 longitudinal, birth cohort to achieve the study objectives. Home food availability was assessed with the Home Food Inventory (HFI) and included fifteen food groups (e.g. fruit and vegetables) and three obesogenic scores (one original and two modified). Food and nutrient intakes were measured using the Block FFQ and included twenty-seven food groups and eighteen nutrients (e.g. vitamins A and C, protein). HFI and FFQ were completed by trained researchers or mothers, respectively, at 24, 36 and 48 months. Repeated-measures ANOVA and Spearman's correlations were used to achieve the study objectives. SETTING: Central Illinois, USA. PARTICIPANTS: Participants were 468 children at 24, 36 and 48 months of age. RESULTS: Availability of less nutritious foods and obesogenic foods and beverages increased as children aged, and availability of both nutritious and less nutritious foods were associated with child food and nutrient intake. The three obesogenic scores demonstrated similar, positive associations with the intake of energy, saturated fat, added sugars and kilocalories from sweets. CONCLUSION: These findings offer novel insight into changes in home food availability and associations with food and nutrient intake during early childhood. Additional attention is needed examining antecedents (e.g. built environments, purchasing behaviours) and consequences (e.g. child diet quality and weight) of home food availability.

Oncology clinical trial disruption during the COVID-19 pandemic: a COVID-19 and cancer outcomes study.

BACKGROUND: COVID-19 disproportionately impacted patients with cancer as a result of direct infection, and delays in diagnosis and therapy. Oncological clinical trials are resource-intensive endeavors that could be particularly susceptible to disruption by the pandemic, but few studies have evaluated the impact of the pandemic on clinical trial conduct. PATIENTS AND METHODS: This prospective, multicenter study assesses the impact of the pandemic on therapeutic clinical trials at two large academic centers in the Northeastern United States between December 2019 and June 2021. The primary objective was to assess the enrollment on, accrual to, and activation of oncology therapeutic clinical trials during the pandemic using an institution-wide cohort of (i) new patient accruals to oncological trials, (ii) a manually curated cohort of patients with cancer, and (ii) a dataset of new trial activations. RESULTS: The institution-wide cohort included 4756 new patients enrolled to clinical trials from December 2019 to June 2021. A major decrease in the numbers of new patient accruals (-46%) was seen early in the pandemic, followed by a progressive recovery and return to higher-than-normal levels (+2.6%). A similar pattern (from -23.6% to +30.4%) was observed among 467 newly activated trials from June 2019 to June 2021. A more pronounced decline in new accruals was seen among academically sponsored trials (versus industry sponsored trials) (P < 0.05). In the manually curated cohort, which included 2361 patients with cancer, non-white patients tended to be more likely taken off trial in the early pandemic period (adjusted odds ratio: 2.60; 95% confidence interval 1.00-6.63), and substantial pandemic-related deviations were recorded. CONCLUSIONS: Substantial disruptions in clinical trial activities were observed early during the pandemic, with a gradual recovery during ensuing time periods, both from an enrollment and an activation standpoint. The observed decline was more prominent among academically sponsored trials, and racial disparities were seen among people taken off trial.

The association between oil spill cleanup-related total hydrocarbon exposure and diabetes.

BACKGROUND: Although evidence suggests relationships between some crude oil components and glycemic dysregulation, no studies have examined oil spill-related chemical exposures in relation to type 2 diabetes mellitus (DM) risk. This study examined the relationship between total hydrocarbon (THC) exposure among workers involved in the 2010 Deepwater Horizon (DWH) oil spill and risk of DM up to 6 years afterward. METHODS: Participants comprised 2660 oil-spill cleanup or response workers in the prospective GuLF Study who completed a clinical exam and had no self-reported DM diagnosis prior to the spill. Maximum THC exposure was estimated with a job-exposure matrix based on interview data and personal measurements taken during cleanup operations. We defined incident DM by self-reported physician diagnosis of DM, antidiabetic medication use, or a measured hemoglobin A1c value ≥ 6.5%. We used log binomial regression to estimate risk ratios (RRs) for DM across ordinal categories of THC exposure. The fully adjusted model controlled for age, sex, race/ethnicity, education, employment status, and health insurance status. We also stratified on clinical body mass index categories. RESULTS: We observed an exposure-response relationship between maximum daily ordinal THC exposure level and incident DM, especially among overweight participants. RRs among overweight participants were 0.99 (95% CI: 0.37, 2.69), 1.46 (95% CI: 0.54, 3.92), and 2.11 (95% CI: 0.78, 5.74) for exposure categories 0.30-0.99 ppm, 1.00-2.99 ppm, and ≥3.00 ppm, respectively (ptrend = 0.03). CONCLUSION: We observed suggestively increasing DM risk with increasing THC exposure level among overweight participants, but not among normal weight or obese participants.

Competing risks analysis of the association between perioperative blood transfusion and long-term outcomes after resection of colorectal cancer.

AIM: Despite numerous reports over three decades, the association between perioperative blood transfusion and long-term outcomes after resection of colorectal cancer remains controversial. This cohort study used competing risks statistical methods to examine the association between transfusion and recurrence and colorectal cancer-specific death after potentially curative and noncurative resection. METHOD: A hospital database provided prospectively recorded clinical, operative and follow-up information. All surviving patients were followed for at least 5 years. Data were analysed by multivariable competing risks regression. RESULTS: From 2575 patients in the period 1995-2010 inclusive, after exclusions, 2334 remained for analysis. Among 1941 who had a potentially curative resection and 393 who had a noncurative resection the transfusion rates were 24.9% and 33.6%, respectively. After potentially curative resection there was no significant bivariate association between transfusion and recurrence (HR 0.93, CI 0.74-1.16, P = 0.499) or between transfusion and colorectal cancer-specific death (HR 1.04, CI 0.82-1.33, P = 0.753). After noncurative resection there was no significant association between transfusion and cancer-specific death (HR 0.93, CI 0.73-1.19, P = 0.560). Multivariable models showed no material effect of potential confounder variables on these results. CONCLUSION: The competing risks findings in this study showed no significant association between perioperative transfusion and recurrence or colorectal cancer-specific death.

Recurrence and cancer-specific death after adjuvant chemotherapy for Stage III colon cancer.

AIM: The recommended standard of care for patients after resection of Stage III colon cancer is adjuvant 5-fluorouracil based chemotherapy - FOLFOX (fluorouracil, leucovorin with oxaliplatin) - or CAPOX (capecitabine, oxaliplatin). This may be modified in older patients or depending on comorbidity. This has been challenged recently as the apparent benefit of adjuvant chemotherapy may arise from improvements in surgery or preoperative imaging or pathology staging. This study compares recurrence and colon-cancer-specific death between patients who received postoperative adjuvant chemotherapy and those who did not. METHOD: Prospectively recorded data from 363 consecutive patients who had a resection for Stage III colonic adenocarcinoma between 1995 and 2010 inclusive were analysed. Surviving patients were followed for at least 5 years. The suitability of patients for chemotherapy was discussed routinely at multidisciplinary team meetings. The incidence of recurrence and colon-cancer-specific death was evaluated by competing risk methods. RESULTS: After adjustment for the competing risk of non-colorectal cancer death, there was no significant difference in recurrence between the 204 patients who received chemotherapy and the 159 who did not [hazard ratio (HR) 0.94, 95% CI 0.66-1.32, P = 0.700) and no significant difference in colon-cancer-specific death (HR 0.73, 95% CI 0.50-1.04, P = 0.084; HR 0.88, 95% CI 0.57-1.36, P = 0.577 after adjustment for relevant covariates). CONCLUSION: These findings question the routine use of chemotherapy after complete mesocolic excision for Stage III colon cancer. Recurrence and cancer-specific death, assessed by competing risk methods, should be the standard outcomes for evaluating the effectiveness of adjuvant chemotherapy after potentially curative resection.

Therapeutic doses of neostigmine, depolarising neuromuscular blockade and muscle weakness in awake volunteers: a double-blind, placebo-controlled, randomised volunteer study.

Neostigmine reverses non-depolarising neuromuscular blockade, but may cause muscle weakness when administered after full recovery of neuromuscular function. We hypothesised that neostigmine in therapeutic doses impairs muscle strength and respiratory function in awake healthy volunteers. Twenty-one volunteers were randomised to receive two doses of either intravenous (i.v.) neostigmine 2.5 mg with glycopyrrolate 450 µg (neostigmine group, n = 14) or normal saline 0.9% (placebo group, n = 7). The first dose was administered immediately after obtaining baseline measurements, and the second dose was administered 15 min later. All 14 volunteers in the neostigmine group received the first dose, mean (SD) 35 (5.8) µg.kg-1 , but only nine of these volunteers agreed to receive the second dose, 34 (3.5) ?g.kg-1 . The primary outcome was hand grip strength. Secondary outcomes were train-of-four ratio, single twitch height, forced expiratory volume in 1 s, forced vital capacity, forced expiratory volume in 1 s/forced vital capacity ratio, oxygen saturation, heart rate and mean arterial pressure. The first dose of intravenous neostigmine with glycopyrrolate resulted in reduced grip strength compared with placebo, -20 (20) % vs. +4.3 (9.9) %, p = 0.0016; depolarising neuromuscular blockade with decreased single twitch height, -14 (11) % vs. -3.8 (5.6) %, p = 0.0077; a restrictive spirometry pattern with decreased predicted forced expiratory volume in 1 s, -15 (12) % vs. -0.47 (3.4) %, p = 0.0011; and predicted forced vital capacity, -20 (12) % vs. -0.59 (3.2) %, p < 0.0001 at 5 min after administration. The second dose of neostigmine with glycopyrrolate further decreased grip strength mean (SD) -41 (23) % vs. +1.0 (15) %, p = 0.0004; single twitch height -25 (15) % vs. -2.5 (6.6) %, p = 0.0030; predicted forced expiratory volume in 1 s -23 (24) % vs. -0.7 (4.4) %, p = 0.0063; and predicted forced vital capacity, -27.1 (22.0) % vs. -0.66 (3.9) %, p = 0.0010. Train-of-four ratio remained unchanged (p = 0.22). In healthy volunteers, therapeutic doses of neostigmine induced significant and dose-dependent muscle weakness, demonstrated by a decrease in maximum voluntary hand grip strength and a restrictive spirometry pattern secondary to depolarising neuromuscular blockade.

Paired methods to measure biofilm killing and removal: a case study with Penicillin G treatment of Staphylococcus aureus biofilm.

Biofilms are microbial aggregates that show high tolerance to antibiotic treatments in vitro and in vivo. Killing and removal are both important in biofilm control, therefore methods that measure these two mechanisms were evaluated in a parallel experimental design. Kill was measured using the single tube method (ASTM method E2871) and removal was determined by video microscopy and image analysis using a new treatment flow cell. The advantage of the parallel test design is that both methods used biofilm covered coupons harvested from a CDC biofilm reactor, a well-established and standardized biofilm growth method. The control Staphylococcus aureus biofilms treated with growth medium increased by 0·6 logs during a 3-h contact time. Efficacy testing showed biofilms exposed to 400 µmol l-1 penicillin G decreased by only 0·3 logs. Interestingly, time-lapse confocal scanning laser microscopy revealed that penicillin G treatment dispersed the biofilm despite being an ineffective killing agent. In addition, no biofilm removal was detected when assays were performed in 96-well plates. These results illustrate that biofilm behaviour and impact of treatments can vary substantially when assayed by different methods. Measuring both killing and removal with well-characterized methods will be crucial for the discovery of new anti-biofilm strategies. SIGNIFICANCE AND IMPACT OF THE STUDY: Biofilms are tolerant to antimicrobial treatments and can lead to persistent infections. Finding new anti-biofilm strategies and understanding their mode-of-action is therefore of high importance. Historically, antimicrobial testing has focused on measuring the decrease in viability. While kill data are undeniably important, measuring biofilm disruption provides equally useful information. Starting with biofilm grown in the same reactor, we paired assessment of biofilm removal using a new treatment-flow-cell and real-time microscopy with kill data collected using the single tube method (ASTM E2871). Pairing these two methods revealed efficient biofilm removal properties of Penicillin G which were not detected during efficacy testing.

Coming of Age in Ireland: the Twilight Zone!

Aim To describe the healthcare needs of adolescent patients inhabiting the 'seventh age of childhood' in our region with a view towards future workforce and infrastructure planning. Methods This is a retrospective descriptive study of patients aged between 14 and 16 years presenting to each of the six hospitals in our hospital group over a 10 year period (01.07.2006-1.07.2016) using electronic databases. Results There were 10,992 hospital admissions, 41,456 outpatient appointments and an average of 1,847 attendances per year at our Emergency Department in this age group. Seventeen percent (n=1,873) of patients were admitted to age appropriate wards. Only 11.3% (n=1,242) of our cohort were admitted under the care of a Paediatrician. Conclusion The Irish healthcare agenda needs to be advanced to ensure the optimal health for this valuable, yet vulnerable generation. Further investment will help shape the fledgling discipline of 'adolescent health' in Ireland.

Borealis-1: a randomized, first-line, placebo-controlled, phase II study evaluating apatorsen and chemotherapy for patients with advanced urothelial cancer.

BACKGROUND: Five-year survival of patients with inoperable, advanced urothelial carcinoma treated with the first-line chemotherapy is 5%-15%. We assessed whether the Hsp27 inhibitor apatorsen combined with gemcitabine plus cisplatin (GC) could improve overall survival (OS) in these patients. PATIENTS AND METHODS: This placebo-controlled, double-blind, phase II trial randomized 183 untreated urothelial carcinoma patients (North America and Europe) to receive GC plus either placebo (N = 62), 600 mg apatorsen (N = 60), or 1000 mg apatorsen (N = 61). In the experimental arm, treatment included loading doses of apatorsen followed by up to six cycles of apatorsen plus GC. Patients receiving at least four cycles could continue apatorsen monotherapy as maintenance until progression or unacceptable toxicity. The primary end point was OS. RESULTS: OS was not significantly improved in the single or combined 600- or 1000-mg apatorsen arms versus placebo [hazard ratio (HR), 0.86 and 0.90, respectively]. Exploratory study of specific statistical modeling showed a trend for improved survival in patients with baseline poor prognostic features treated with 600 mg apatorsen compared with placebo (HR = 0.72). Landmark analysis of serum Hsp27 (sHsp27) levels showed a trend toward survival benefit for poor-prognosis patients in 600- and 1000-mg apatorsen arms who achieved lower area under the curve sHsp27 levels, compared with the placebo arm (HR = 0.45 and 0.62, respectively). Higher baseline circulating tumor cells (≥5 cells/7.5 ml) was observed in patients with poor prognosis in correlation with poor survival. Treatment-emergent adverse events were manageable and more common in both apatorsen-treatment arms. CONCLUSIONS: Even though apatorsen combined with standard chemotherapy did not demonstrate a survival benefit in the overall study population, patients with poor prognostic features might benefit from this combination. Serum Hsp27 levels may act as a biomarker to predict treatment outcome. Further exploration of apatorsen in poor-risk patients is warranted.

A phase I dose-escalation study of apatorsen (OGX-427), an antisense inhibitor targeting heat shock protein 27 (Hsp27), in patients with castration-resistant prostate cancer and other advanced cancers.

BACKGROUND: Heat shock protein 27 (Hsp27) is a chaperone protein that regulates cell survival via androgen receptor and other signaling pathways, thereby mediating cancer progression. Apatorsen (OGX-427) is a 2'-methoxyethyl-modified antisense oligonucleotide that inhibits Hsp27 expression. This study evaluated the safety profile and recommended phase II dosing of apatorsen in patients with advanced cancer. PATIENTS AND METHODS: Patients with castration-resistant prostate (CRPC), breast, ovary, lung, or bladder cancer were enrolled to this phase I dose-escalation study. Apatorsen was administered i.v. weekly in 21-day cycles following 3 loading doses and over 5 dose levels (200-1000 mg). Apatorsen plasma concentrations, circulating tumor cells (CTCs) and CTC Hsp27 expression, and serum Hsp27 levels were evaluated. RESULTS: Forty-two patients were accrued, of which 52% had CRPC. Patients were heavily pretreated, with 57% having had ≥3 prior chemotherapy regimens. During the loading dose/cycle 1 and overall study period, 93% and 100% of patients (N = 42) experienced treatment-related adverse events, respectively; most were grade 1-2 and included chills, pruritus, flushing, prolonged aPTT, lymphopenia, and anemia. One patient experienced a dose-limiting toxicity at the 600 mg dose level (intracranial hemorrhage in a previously undiagnosed brain metastasis). A maximum tolerated dose was not defined. Apatorsen Cmax increased proportionally with dose. Decreases in tumor markers and declines in CTCs were observed, with a prostate-specific antigen decline >%50% occurring in 10% of patients with CRPC; 29/39 assessable patients (74%) had reductions from ≥5 CTC/7.5 ml at baseline to <5 CTC/7.5 ml post-treatment. Twelve patients had stable measurable disease as best response. CONCLUSIONS: Apatorsen was tolerated at the highest dose evaluated (1000 mg). Single-agent activity was suggested by changes in tumor markers, CTC, and stable measurable disease. Phase II studies evaluating apatorsen are underway. CLINICALTRIALSGOV ID: NCT00487786.

Long-term results following an anatomically based surgical technique for resection of colon cancer: a comparison with results from complete mesocolic excision.

AIM: Complete mesocolic excision (CME) has been advocated as likely to improve the long-term oncological outcome of colon cancer resection, although there is a paucity of long-term results in the literature. The aim of this study was to supplement our previously published results on colon cancer resection based on a standardized technique of precise dissection along anatomical planes with high vascular ligation and to compare our long-term results with those of recent European studies of CME. METHOD: Data were drawn from a prospective hospital registry of consecutive resections for colon cancer between 1996 and 2007, including follow-up to the end of 2012. The principal outcomes from potentially curative resections were 5-year Kaplan-Meier rates of local recurrence, systemic recurrence, overall survival and cancer-specific survival. Secondary outcomes for all resections were postoperative complications, number of lymph nodes retrieved and R0 status. RESULTS: For 779 potentially curative resections the local recurrence rate was 2.1% (95% CI 1.3-3.4), the systemic recurrence rate was 10.2% (95% CI 8.1-12.7), the 5-year overall survival rate was 76.2% (95% CI 73.0-79.0) and the cancer-specific survival rate was 89.8% (95% CI 87.3-91.9). For all 905 resections, rates of 14 surgical complications were low and not dissimilar to those in a comparable study. The median lymph node count was 15 (range 0-113). R0 status was confirmed in 883/905 patients (97.6%; 95% CI 96.4-98.5). CONCLUSION: For colon cancer, meticulous dissection along anatomical planes together with high vascular ligation results in few complications, a high R0 rate, low recurrence and high survival.

Speciation of radiocesium and radioiodine in aerosols from Tsukuba after the Fukushima nuclear accident.

Aerosol samples were collected from Tsukuba, Japan, soon after the 2011 Fukushima nuclear accident and analyzed for speciation of radiocesium and radioiodine to explore their chemical behavior and isotopic ratios after the release. Most (134)Cs and (137)Cs were bound in organic matter (53­91%) and some in water-soluble fractions (5­15%), whereas a negligible proportion of radiocesium remained in minerals. This pattern suggests that sulfate salts and organic matter may be the main carrier of Cs-bearing particles. The (129)I in aerosol samples is contained in various proportions as soluble inorganic iodine (I(­) and IO3(­)), soluble organic iodine, and unextractable iodine. The measured mean (129)I/(131)I atomic ratio of 16.0 ± 2.2 is in good agreement with that measured from rainwater and consistent with ratios measured in surface soil samples. Together with other aerosols and seawater samples, an initial (129)I/(137)Cs activity ratio of ∼4 × 10(­7) was obtained. In contrast to the effectively constant (134)Cs/(137)Cs activity ratios (1.04 ± 0.04) and (129)I/(131)I atomic ratios (16.0 ± 2.2), the (129)I/(137)Cs activity ratios scattered from 3.5 × 10(­7) to 5 × 10(­6) and showed temporally and spatially different dispersion and deposition patterns between radiocesium and radioiodine. These findings confirm that (129)I, instead of (137)Cs, should be considered as a proxy for (131)I reconstruction.

Fluoroscopic versus laparoscopic implantation of peritoneal dialysis catheters: a retrospective cohort study.

PURPOSE: A previous clinical trial showed that radiologic insertion of first peritoneal dialysis (PD) catheters by modified Seldinger technique is noninferior to laparoscopic surgery in patients at low risk in a clinical trial setting. The present cohort study was performed to confirm clinical effectiveness of radiologic insertion in everyday practice, including insertion in patients with expanded eligibility criteria and by fellows in training. MATERIALS AND METHODS: Between 2004 and 2009, 286 PD catheters were inserted in 249 patients, 133 with fluoroscopic guidance in the radiology department and 153 by laparoscopic surgery. Survival analyses were performed with the primary outcome of complication-free catheter survival and secondary outcomes of overall catheter survival and patient survival. Outcomes were assessed at last follow-up, as long as 365 days after PD catheter insertion. RESULTS: In the radiologic group, unadjusted 365-day complication-free catheter, overall catheter, and patient survival rates were 22.6%, 81.2%, and 82.7%, respectively, compared with 22.9% (P = .52), 76.5% (P = .4), and 92.8% (P = .01), respectively, in the laparoscopic group. Frequencies of individual complications were similar between groups. Adjusting for patient age, comorbidity, and previous PD catheter, the hazard ratio (HR) for catheter complications by radiologic versus laparoscopic insertion is 0.90 (95% confidence interval [CI], 0.62-1.31); the HR for overall catheter survival is 1.25 (95% CI, 0.59-2.65); and that for death is 2.47 (95% CI, 0.84-7.3). CONCLUSIONS: Radiologic PD catheter insertion is a clinically effective alternative to laparoscopic surgery, although there was poorer long-term survival with radiologic catheter placement, possibly because of preferential selection of radiologic insertion for more frail patients.

Reliability, factorial validity, and interrelationships of five commonly used change of direction speed tests.

Change of direction speed (CODS) is often considered a main determinant of successful performance in many team sports and is routinely measured using field-based tests. However, controversy regarding test selection still exists based upon the reliability and specificity of the tests. The purpose of this study was to determine and compare the reliability, factorial validity, and interrelationships of five frequently used CODS tests (Illinois, L-Run, Pro-Agility, T-test, and 505). Forty-four physical education students (male n = 24; female n = 20; age; 16.7 ± 0.6), who compete within team sports, to varying levels of competition, participated in this study. Three trials for each of the five tests were recorded. All tests had high (intraclass correlation coefficient) test-retest reliability (r = 0.88-0.95) and low typical percentage error (1.95-2.40%). The principle component factor analysis resulted in the extraction of one significant component which explained 89.52% of the total variance. All selected tests were positively and strongly correlated (r = 0.84-0.89). Based upon the results of this study, it was concluded that all tests are highly reliable and valid measures of CODS, with all tests assessing a general athletic ability to change direction. Future research should investigate the factorial validity of the CODS test within homogenous samples.

A discrete-to-continuum model for the human cornea with application to keratoconus.

We introduce a discrete mathematical model for the mechanical behaviour of a planar slice of human corneal tissue, in equilibrium under the action of physiological intraocular pressure (IOP). The model considers a regular (two-dimensional) network of structural elements mimicking a discrete number of parallel collagen lamellae connected by proteoglycan-based chemical bonds (crosslinks). Since the thickness of each collagen lamella is small compared to the overall corneal thickness, we upscale the discrete force balance into a continuum system of partial differential equations and deduce the corresponding macroscopic stress tensor and strain energy function for the micro-structured corneal tissue. We demonstrate that, for physiological values of the IOP, the predictions of the discrete model converge to those of the continuum model. We use the continuum model to simulate the progression of the degenerative disease known as keratoconus, characterized by a localized bulging of the corneal shell. We assign a spatial distribution of damage (i.e. reduction of the stiffness) to the mechanical properties of the structural elements and predict the resulting macroscopic shape of the cornea, showing that a large reduction in the element stiffness results in substantial corneal thinning and a significant increase in the curvature of both the anterior and posterior surfaces.

A microRNA diagnostic biomarker for amyotrophic lateral sclerosis.

Blood-based diagnostic biomarkers for amyotrophic lateral sclerosis will improve patient outcomes and positively impact novel drug development. Critical to the development of such biomarkers is robust method validation, optimization and replication with adequate sample sizes and neurological disease comparative blood samples. We sought to test an amyotrophic lateral sclerosis biomarker derived from diverse samples to determine if it is disease specific. Extracellular vesicles were extracted from blood plasma obtained from individuals diagnosed with amyotrophic lateral sclerosis, primary lateral sclerosis, Parkinson's disease and healthy controls. Immunoaffinity purification was used to create a neural-enriched extracellular vesicle fraction. MicroRNAs were measured across sample cohorts using real-time polymerase chain reaction. A Kruskal-Wallis test was used to assess differences in plasma microRNAs followed by post hoc Mann-Whitney tests to compare disease groups. Diagnostic accuracy was determined using a machine learning algorithm and a logistic regression model. We identified an eight-microRNA diagnostic signature for blood samples from amyotrophic lateral sclerosis patients with high sensitivity and specificity and an area under the curve calculation of 98% with clear statistical separation from neurological controls. The eight identified microRNAs represent disease-related biological processes consistent with amyotrophic lateral sclerosis. The direction and magnitude of gene fold regulation are consistent across four separate patient cohorts with real-time polymerase chain reaction analyses conducted in two laboratories from diverse samples and sample collection procedures. We propose that this diagnostic signature could be an aid to neurologists to supplement current clinical metrics used to diagnose amyotrophic lateral sclerosis.

Iodine isotopes in precipitation: temporal responses to (129)i emissions from the fukushima nuclear accident.

The Fukushima Dai-ichi Nuclear Power Plant accident in 2011 has released a large amount of radionuclides to the atmosphere, and the radioactive plume has been dispersed to a large area in Europe and returned to Asia. To explore long-term trend of the Fukushima-derived radioactive plume and the behavior of harmful radioiodine in the atmosphere, long-term precipitation samples have been collected over 2010-2012 at Fukushima, Japan for determination of long-lived (129)I. It was observed that (129)I concentrations of 1.2 × 10(8) atom/L in 2010 before the accident dramatically increased by ∼4 orders of magnitude to 7.6 × 10(11) atom/L in March 2011 immediately after the accident, with a (129)I/(127)I ratio up to 6.9 × 10(-5). Afterward, the (129)I concentrations in precipitation decreased exponentially to ∼3 × 10(9) atom/L by October 2011 with a half-life of about 29 days. This declining trend of (129)I concentrations in precipitation was interrupted around October 2011 by a new input of (129)I to the atmosphere following a second exponential decrease. Such a cycle has occurred three times until the present. This temporal variation can be attributed to alternating (129)I dispersion and resuspension from the contaminated local environment. A (129)I/(131)I atomic ratio of 16 ± 1 obtained from rainwater samples is comparable with a value estimated for surface soil samples. (129)I results from Denmark suggest an insignificant effect of (129)I released from Fukushima to the (129)I levels in Europe.

Lipid profiles and persisting inflammation following critical illness in a central Australian population: a prospective longitudinal observational study.

No published data exist following the changes in lipid profile during and after an episode of acute illness for the Australian Indigenous population. This paper presents data focusing on lipid profiles and inflammatory markers in a group of survivors of critical illness in Central Australia, prospectively recruited to a larger trial exploring the medium-term sequelae of an intensive care unit admission. This data confirm that lipid profiles in acute illness are deranged, and that recovery may differ between indigenous and non-indigenous populations.