Society of Critical Care Medicine Guidelines on Glycemic Control for Critically Ill Children and Adults 2024.

RATIONALE: Maintaining glycemic control of critically ill patients may impact outcomes such as survival, infection, and neuromuscular recovery, but there is equipoise on the target blood levels, monitoring frequency, and methods. OBJECTIVES: The purpose was to update the 2012 Society of Critical Care Medicine and American College of Critical Care Medicine (ACCM) guidelines with a new systematic review of the literature and provide actionable guidance for clinicians. PANEL DESIGN: The total multiprofessional task force of 22, consisting of clinicians and patient/family advocates, and a methodologist applied the processes described in the ACCM guidelines standard operating procedure manual to develop evidence-based recommendations in alignment with the Grading of Recommendations Assessment, Development, and Evaluation Approach (GRADE) methodology. Conflict of interest policies were strictly followed in all phases of the guidelines, including panel selection and voting. METHODS: We conducted a systematic review for each Population, Intervention, Comparator, and Outcomes question related to glycemic management in critically ill children (≥ 42 wk old adjusted gestational age to 18 yr old) and adults, including triggers for initiation of insulin therapy, route of administration, monitoring frequency, role of an explicit decision support tool for protocol maintenance, and methodology for glucose testing. We identified the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the GRADE approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak or as a good practice statement. In addition, "In our practice" statements were included when the available evidence was insufficient to support a recommendation, but the panel felt that describing their practice patterns may be appropriate. Additional topics were identified for future research. RESULTS: This guideline is an update of the guidelines for the use of an insulin infusion for the management of hyperglycemia in critically ill patients. It is intended for adult and pediatric practitioners to reassess current practices and direct research into areas with inadequate literature. The panel issued seven statements related to glycemic control in unselected adults (two good practice statements, four conditional recommendations, one research statement) and seven statements for pediatric patients (two good practice statements, one strong recommendation, one conditional recommendation, two "In our practice" statements, and one research statement), with additional detail on specific subset populations where available. CONCLUSIONS: The guidelines panel achieved consensus for adults and children regarding a preference for an insulin infusion for the acute management of hyperglycemia with titration guided by an explicit clinical decision support tool and frequent (≤ 1 hr) monitoring intervals during glycemic instability to minimize hypoglycemia and against targeting intensive glucose levels. These recommendations are intended for consideration within the framework of the patient's existing clinical status. Further research is required to evaluate the role of individualized glycemic targets, continuous glucose monitoring systems, explicit decision support tools, and standardized glycemic control metrics.

Associations between urine glyphosate levels and metabolic health risks: insights from a large cross-sectional population-based study.

BACKGROUND: The prevalence of metabolic syndrome (MetS) in American adults increased from 37.6% in the 2011-12 period to 41.8% in 2017-2018. Environmental exposure, particularly to common compounds such as glyphosate, has drawn increasing attention as a potential risk factor. METHODS: We employed three cycles of data (2013-2018) from the National Health and Nutrition Examination Survey (NHANES) in a cross-sectional study to examine potential associations between urine glyphosate measurements and MetS incidence. We first created a MetS score using exploratory factor analysis (EFA) of the International Diabetes Federation (IDF) criteria for MetS, with data drawn from the 2013-2018 NHANES cycles, and validated this score independently on an additional associated metric, the albumin-to-creatinine (ACR) ratio. The score was validated via a machine learning approach in predicting the ACR score via binary classification and then used in multivariable regression to test the association between quartile-categorized glyphosate exposure and the MetS score. RESULTS: In adjusted multivariable regressions, regressions between quartile-categorized glyphosate exposure and MetS score showed a significant inverted U-shaped or saturating dose‒response profile, often with the largest effect for exposures in quartile 3. Exploration of potential effect modification by sex, race, and age category revealed significant differences by race and age, with older people (aged > 65 years) and non-Hispanic African American participants showing larger effect sizes for all exposure quartiles. CONCLUSIONS: We found that urinary glyphosate concentration is significantly associated with a statistical score designed to predict MetS status and that dose-response coefficient is nonlinear, with advanced age and non-Hispanic African American, Mexican American and other Hispanic participants exhibiting greater effect sizes.

Long-term risk of carotid stenosis and cerebrovascular disease after radiation therapy for head and neck cancer.

BACKGROUND: Recipients of radiation therapy (RT) for head and neck cancer (HNC) are at significantly increased risk for carotid artery stenosis (CAS) and cerebrovascular disease (CVD). We sought to determine (1) cumulative incidences of CAS and CVD among HNC survivors after RT and (2) whether CAS is associated with a RT dose response effect. METHODS: This single-institution retrospective cohort study examined patients with nonmetastatic HNC who completed (chemo)RT from January 2000 through October 2020 and subsequently received carotid imaging surveillance ≤2 years following RT completion and, in the absence of CAS, every 3 years thereafter. Exclusion criteria included history of known CAS/CVD. Asymptomatic CAS was defined as ≥50% reduction of luminal diameter, symptomatic CAS as stroke or transient ischemic attack, and composite CAS as asymptomatic or symptomatic CAS. RESULTS: Of 628 patients undergoing curative intent RT for HNC, median follow-up was 4.8 years (interquartile range, 2.6-8.3), with 97 patients followed ≥10 years. Median age was 61 years and 69% of patients received concurrent chemotherapy and 28% were treated postoperatively. Actuarial 10-year incidences of asymptomatic, symptomatic, and composite CAS were 29.6% (95% CI, 23.9-35.5), 10.1% (95% CI, 7.0-13.9), and 27.2% (95% CI, 22.5-32.1), respectively. Multivariable Cox models significant association between asymptomatic CAS and absolute carotid artery volume receiving ≥10 Gy (per mL: hazard ratio, 1.09; 95% CI, 1.02-1.16). CONCLUSIONS: HNC survivors are at high risk for post-RT CAS. A dose response effect was observed for asymptomatic CAS at doses as low as 10 Gy. PLAIN LANGUAGE SUMMARY: Recipients of radiation therapy for head and neck cancer are at significantly increased risk for carotid artery stenosis and cerebrovascular disease. However, carotid artery screening is not routinely performed among head and neck survivors following radiation therapy. In this single-institution retrospective cohort study, patients with head and neck cancer were initially screened for carotid artery stenosis ≤2 years following radiation therapy completion, then every 3 years thereafter. The 10-year actuarial incidence of carotid artery stenosis was >25% and stroke/transient ischemic attack >10%. Multivariable analysis demonstrated significant associations between asymptomatic carotid artery stenosis and artery volumes receiving ≥10 Gy.

Effects of mixtures of polychlorinated biphenyls (PCBs) and three organochlorine pesticides on cognitive function differ between older Mohawks at Akwesasne and older adults in NHANES.

BACKGROUND: Akwesasne Mohawks has been exposed to high concentrations of polychlorinated biphenyls (PCBs) and background levels of organochlorine pesticides, hexachlorobenzene (HCB), dichlorodiphenyl dichloroethylene (DDE), and mirex. We have previously reported relative contributions to the mixture of low- and high-chlorinated PCBs, HCB, and DDE on cognitive decrements in Mohawks of various ages. OBJECTIVE: This study examines differences in the mixture effects of PCB congener groups, HCB, DDE, and mirex on cognitive function in older Mohawks and less PCB-exposed older adults from the National Health and Nutrition Examination Survey (NHANES) 1999-2002 cycles. METHODS: We used Bayesian kernel machine regression (BKMR) to evaluate the mixture effects of different PCB congener groups, HCB, DDE, and mirex on cognitive function in both populations. Models were adjusted for age, sex, education levels, and race/ethnicity focusing on individuals 60 years and older. RESULTS: Older Mohawks had 3-fold higher mean total PCB concentrations and 1.8-fold higher mirex, but slightly lower mean DDE and HCB levels than NHANES older adults. Higher mixture concentrations were significantly associated with greater cognitive decline. In older Mohawks, low- and high-chlorinated PCBs, HCB, and DDE contributed to the cognitive score decline. In contrast, score decline in older NHANES adults were primarily from high-chlorinated PCBs and DDE with a threshold dose of approximately 2.08-2.27 ng/g and 2.02-2.40 ng/g, respectively. CONCLUSION: Mixtures of PCBs and organochlorine pesticides increase the risk of cognitive decline in both older Mohawks and NHANES older adults. However, contributions to these mixture effects show significant differences. In older Mohawks, high- and low-chlorinated PCBs, DDE, and HCB are the primary contributors, while high-chlorinated PCBs and DDE are important contributors in NHANES older adults. Due to chronic heavy exposures to PCBs, older Mohawks had a significantly increased risk of cognitive decline compared to general older adults from NHANES.

State of gaseous air pollutants and resulting health effects in Karachi, Pakistan.

Karachi, Pakistan, is a priority site for air pollution research due to high emissions of air pollutants from vehicular traffic, industrial activities, and biomass burning, as well as rapid growth in population. The objectives of this study were to investigate the levels of gaseous pollutants (NO, NO2, O3, HNO3, and SO2) in Karachi, to determine temporal and seasonal variations, to compare Karachi's air quality with other urban centers, to identify relationships with meteorological conditions, to identify source characterization, and to perform a backward-in-time trajectory analysis and a health impact assessment. Daily samples of gaseous pollutants were collected for six consecutive weeks in each of the four seasons for a year. Daily maximum concentrations of NO (90 parts per billion by volume (ppbv)), NO2 (28.1 ppbv), O3 (57.8 ppbv), and SO2 (331 ppbv) were recorded in fall, while HNO3 (9129 parts per trillion by volume (pptv)) was recorded in spring. Seasonal average concentrations were high in winter for NO (9.47 ± 7.82 ppbv), NO2 (4.84 ± 3.35 ppbv), and O3 (8.92 ± 7.65 ppbv), while HNO3 (629 ± 1316 pptv) and SO2 (20.2 ± 39.4 ppbv) were high in spring and fall, respectively. The observed SO2 seasonal average concentration in fall (20.2 ± 39.4) was 5 times higher than that in summer (3.97 ± 2.77) with the fall 24-h average (120 ppbv) exceeding the WHO daily guideline (7.64 ppbv) by a factor of about 15.7. A health impact assessment estimated an increase of 1200 and 569 deaths due to short-term exposure to SO2 in fall and spring, respectively. Chronic daily intake estimated risk per 1000 was 0.99, 0.47, 0.45, and 0.26 for SO2 in fall, NO in winter, O3 in winter, and NO2 in spring, respectively. This study confirms the effect of poor urban air quality on public health and demonstrated the influence of photochemical reactions as well as unfavorable meteorological conditions on the formation of secondary pollutants.

Effects of glyphosate and glyphosate-based herbicides like Roundup™ on the mammalian nervous system: A review.

Glyphosate is the active ingredient in glyphosate-based herbicides (GBHs), such as Roundup™, the most widely used herbicides in the world. Glyphosate targets an essential enzyme in plants that is not found in animals. However, both glyphosate and GBHs are rated as Group 2A, probable human carcinogens, and also have documented effects on reproduction, acting as endocrine disruptive chemicals. We have reviewed reports of the effects of glyphosate and GBHs on mammalian nervous system function. As with several other herbicides, GBHs exposure has been associated with an increased risk of Parkinson's Disease and death of neurons in the substantia nigra. There is also some evidence implicating Roundup™ in elevated risk of autism. Other studies have shown the effects of GBHs on synaptic transmission in animal and cellular studies. The major mechanism of action appears to be oxidative stress, accompanied by mitochondrial dysfunction. In addition, some gut bacteria utilize the enzyme used by plants, and glyphosate and GBHs use has been shown to alter the gut microbiome. There is a large and growing body of evidence that the gut microbiome alters susceptibility to great number of human diseases, including nervous system function. The weight of the evidence indicates that in addition to cancer and reproductive effects, glyphosate and GBHs have significant adverse effects on the brain and behavior and increase the risk of at least some serious neurological diseases.

Neutrophils promote tumor resistance to radiation therapy.

Nearly two-thirds of cancer patients are treated with radiation therapy (RT), often with the intent to achieve complete and permanent tumor regression (local control). RT is the primary treatment modality used to achieve local control for many malignancies, including locally advanced cervical cancer, head and neck cancer, and lung cancer. The addition of concurrent platinum-based radiosensitizing chemotherapy improves local control and patient survival. Enhanced outcomes with concurrent chemoradiotherapy may result from increased direct killing of tumor cells and effects on nontumor cell populations. Many patients treated with concurrent chemoradiotherapy exhibit a decline in neutrophil count, but the effects of neutrophils on radiation therapy are controversial. To investigate the clinical significance of neutrophils in the response to RT, we examined patient outcomes and circulating neutrophil counts in cervical cancer patients treated with definitive chemoradiation. Although pretreatment neutrophil count did not correlate with outcome, lower absolute neutrophil count after starting concurrent chemoradiotherapy was associated with higher rates of local control, metastasis-free survival, and overall survival. To define the role of neutrophils in tumor response to RT, we used genetic and pharmacological approaches to deplete neutrophils in an autochthonous mouse model of soft tissue sarcoma. Neutrophil depletion prior to image-guided focal irradiation improved tumor response to RT. Our results indicate that neutrophils promote resistance to radiation therapy. The efficacy of chemoradiotherapy may depend on the impact of treatment on peripheral neutrophil count, which has the potential to serve as an inexpensive and widely available biomarker.

'COVID on Country': an innovative model safely supporting high-risk patients in Central Australia.

In January 2022, as the COVID pandemic reached remote communities in Central Australia, The Northern Territory Health Central Australian Regional Health Service and the Royal Flying Doctor Service (RFDS) executed 'COVID on Country', a program designed to triage cases and to implement treatment and clinical review of individuals in their community without the need to be relocated to larger centres for safe provision of care. The program assessed patient factors and community/capacity factors to triage and enact pathways. Remote living people who qualified for the program or who declined aeromedical retrieval, were provided with comprehensive clinical support, including administration of intravenous sotrovimab by daily scheduled visits to all affected communities by a doctor transported on an RFDS plane. Evaluation of the program demonstrated that it was a safe and effective way to provide complex care in a culturally safe manner.

Health disparities: Intracellular consequences of social determinants of health.

Health disparities exist dependent on socioeconomic status, living conditions, race/ethnicity, diet, and exposures to environmental pollutants. Herein, the various exposures contributing to a person's exposome are collectively considered social determinants of health (SDOH), and the SDOH-exposome impacts health more than health care. This review discusses the extent of evidence of the physiologic consequences of these exposures at the intracellular level. We consider how the SDOH-exposome, which captures how individuals live, work and age, induces cell processes that modulate a conceptual "redox rheostat." Like an electrical resistor, the SDOH-exposome, along with genetic predisposition and age, regulate reductive and oxidative (redox) stress circuits and thereby stimulate inflammation. Regardless of the source of the SDOH-exposome that induces chronic inflammation and immunosenescence, the outcome influences cardiometabolic diseases, cancers, infections, sepsis, neurodegeneration and autoimmune diseases. The endogenous redox rheostat is connected with regulatory molecules such as NAD+/NADH and SIRT1 that drive redox pathways. In addition to these intracellular and mitochondrial processes, we discuss how the SDOH-exposome can influence the balance between metabolism and regulation of immune responsiveness involving the two main molecular drivers of inflammation, the NLRP3 inflammasome and NF-κB induction. Mitochondrial and inflammasome activities play key roles in mediating defenses against pathogens and controlling inflammation before diverse cell death pathways are induced. Specifically, pyroptosis, cell death by inflammation, is intimately associated with common disease outcomes that are influenced by the SDOH-exposome. Redox influences on immunometabolism including protein cysteines and ion fluxes are discussed regarding health outcomes. In summary, this review presents a translational research perspective, with evidence from in vitro and in vivo models as well as clinical and epidemiological studies, to outline the intracellular consequences of the SDOH-exposome that drive health disparities in patients and populations. The relevance of this conceptual and theoretical model considering the SARS-CoV-2 pandemic are highlighted. Finally, the case of asthma is presented as a chronic condition that is modified by adverse SDOH exposures and is manifested through the dysregulation of immune cell redox regulatory processes we highlight in this review.

Vanadium Stable Isotopes in Biota of Terrestrial and Aquatic Food Chains.

Vanadium, a potentially toxic metal, is enriched in the environment from anthropogenic releases, particularly during fossil fuel production and use and steel manufacturing. Metal stable isotopes are sophisticated tools to trace pollution; however, only recent analytical advances have allowed for the accurate and precise measurement of vanadium isotope ratios (δ51V). To examine its potential as a tracer in terrestrial and aquatic ecosystems, δ51V was measured in soil, plant, lichen, marten, and lake sediment from sites near vanadium emissions at oil sands mines (Alberta, Canada) and in the sediment and biota (algae, zooplankton, fish) from a remote subarctic lake (Northwest Territories, Canada). Samples from Alberta had distinct δ51V values with marten liver the lowest (-1.7 ± 0.3‰), followed by lichen (-0.9 ± 0.1‰), soil (-0.7 ± 0.1‰), sediment (-0.5 ± 0.2‰), and plant root (-0.3 ± 0.2‰). Average values were lower than Alberta bitumen and petroleum coke (-0.1 ± 0.1‰). Plant roots had systematically higher δ51V than the soil from which they grew (Δ51Vplant-soil = 0.4 ± 0.1‰), while δ51V of lichen and aquatic biota were lower (0.1-0.3‰) than likely crustal sources. These δ51V measurements in terrestrial and aquatic biota demonstrate promise for tracer applications, although further study of its biological fractionation is needed.

Interactions among thyroid hormones and serum lipid levels in association with PCB exposure in the Mohawk Akwesasne population.

Alterations in thyroid function and serum lipid levels were assessed in relation to exposure to polychlorinated biphenyls (PCBs) and three chlorinated pesticides (DDE, hexachorobenzene and mirex) in a sample of Akwesasne Mohawk adults. This population is highly exposed to PCBs because of living in close proximity to three aluminum foundries that used PCBs as hydraulic fluids, which then contaminated local fish, wildlife, water, air and soils. The goal was to assess interactions between thyroid function (TSH, T3, T4 and fT4) and serum lipids (cholesterol, triglycerides and total serum lipids) in relation to concentrations of 101 PCB congeners and three chlorinated pesticides. Previous studies in this population have shown that elevated concentrations of PCBs resulted in suppression of thyroid function in adolescents, and increased risk of clinical hypothyroidism in adults, as well as an elevation in serum lipids. However in adjusted analyses of PCB concentrations of 703 adults we find only small and inconsistent associations between serum PCB levels and thyroid function. The most striking observations were strong significant positive associations between TSH and T3 with serum lipids and a negative association with fT4 in women. Because elevated serum lipids increase risks of other diseases the respective roles of thyroid hormones and PCBs in regulation of serum lipids requires additional study.

The Critical Importance of Molecular Biomarkers and Imaging in the Study of Electrohypersensitivity. A Scientific Consensus International Report.

Clinical research aiming at objectively identifying and characterizing diseases via clinical observations and biological and radiological findings is a critical initial research step when establishing objective diagnostic criteria and treatments. Failure to first define such diagnostic criteria may lead research on pathogenesis and etiology to serious confounding biases and erroneous medical interpretations. This is particularly the case for electrohypersensitivity (EHS) and more particularly for the so-called "provocation tests", which do not investigate the causal origin of EHS but rather the EHS-associated particular environmental intolerance state with hypersensitivity to man-made electromagnetic fields (EMF). However, because those tests depend on multiple EMF-associated physical and biological parameters and have been conducted in patients without having first defined EHS objectively and/or endpoints adequately, they cannot presently be considered to be valid pathogenesis research methodologies. Consequently, the negative results obtained by these tests do not preclude a role of EMF exposure as a symptomatic trigger in EHS patients. Moreover, there is no proof that EHS symptoms or EHS itself are caused by psychosomatic or nocebo effects. This international consensus report pleads for the acknowledgement of EHS as a distinct neuropathological disorder and for its inclusion in the WHO International Classification of Diseases.

Neural-specific deletion of the focal adhesion adaptor protein paxillin slows migration speed and delays cortical layer formation.

Paxillin and Hic-5 are homologous focal adhesion adaptor proteins that coordinate cytoskeletal rearrangements in response to integrin signaling, but their role(s) in cortical development are unknown. Here, we find that Hic-5-deficient mice are postnatal viable with normal cortical layering. Mice with a neural-specific deletion of paxillin are also postnatal viable, but show evidence of a cortical neuron migration delay that is evident pre- and perinatally, but is not detected at postnatal day 35 (P35). This phenotype is not modified by Hic-5 deficiency (double knockout). Specific deletion of paxillin in postmitotic neurons using Nex-Cre-mediated recombination as well as in utero electroporation of a Cre-expression construct identified a cell-autonomous requirement for paxillin in migrating neurons. Paxillin-deficient neurons have shorter leading processes that exhibited multiple swellings in comparison with control. Multiphoton imaging revealed that paxillin-deficient neurons migrate ∼30% slower than control neurons. This phenotype is similar to that produced by deletion of focal adhesion kinase (FAK), a signaling partner of paxillin, and suggests that paxillin and FAK function cell-autonomously to control migrating neuron morphology and speed during cortical development.

ICU and Ventilator Mortality Among Critically Ill Adults With Coronavirus Disease 2019.

OBJECTIVES: To determine mortality rates among adults with critical illness from coronavirus disease 2019. DESIGN: Observational cohort study of patients admitted from March 6, 2020, to April 17, 2020. SETTING: Six coronavirus disease 2019 designated ICUs at three hospitals within an academic health center network in Atlanta, Georgia, United States. PATIENTS: Adults greater than or equal to 18 years old with confirmed severe acute respiratory syndrome-CoV-2 disease who were admitted to an ICU during the study period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 217 critically ill patients, mortality for those who required mechanical ventilation was 35.7% (59/165), with 4.8% of patients (8/165) still on the ventilator at the time of this report. Overall mortality to date in this critically ill cohort is 30.9% (67/217) and 60.4% (131/217) patients have survived to hospital discharge. Mortality was significantly associated with older age, lower body mass index, chronic renal disease, higher Sequential Organ Failure Assessment score, lower PaO2/FIO2 ratio, higher D-dimer, higher C-reactive protein, and receipt of mechanical ventilation, vasopressors, renal replacement therapy, or vasodilator therapy. CONCLUSIONS: Despite multiple reports of mortality rates exceeding 50% among critically ill adults with coronavirus disease 2019, particularly among those requiring mechanical ventilation, our early experience indicates that many patients survive their critical illness.

Extremely low frequency electromagnetic fields and cancer: How source of funding affects results.

While there has been evidence indicating that excessive exposure to magnetic fields from 50 to 60 Hz electricity increases risk of cancer, many argue that the evidence is inconsistent and inconclusive. This is particularly the case regarding magnetic field exposure and childhood leukemia. A major goal of this study is to examine how source of funding influences the reported results and conclusions. Several meta-analyses dating from about 2000 all report significant associations between exposure and risk of leukemia. By examining subsequent reports on childhood leukemia it is clear that almost all government or independent studies find either a statistically significant association between magnetic field exposure and childhood leukemia, or an elevated risk of at least OR = 1.5, while almost all industry supported studies fail to find any significant or even suggestive association. A secondary goal of this report is to examine the level of evidence for exposure and elevated risk of various adult cancers. Based on pooled or meta-analyses as well as subsequent peer-reviewed studies there is strong evidence that excessive exposure to magnetic fields increases risk of adult leukemia, male and female breast cancer and brain cancer. There is less convincing but suggestive evidence for elevations in several other cancer types. There is less clear evidence for bias based on source of funding in the adult cancer studies. There is also some evidence that both paternal and maternal prenatal exposure to magnetic fields results in an increased risk of leukemia and brain cancer in offspring. When one allows for bias reflected in source of funding, the evidence that magnetic fields increase risk of cancer is neither inconsistent nor inconclusive. Furthermore adults are also at risk, not just children, and there is strong evidence for cancers in addition to leukemia, particularly brain and breast cancer.

Research approvals iceberg: helping it melt away.

BACKGROUND: In their paper "Research approvals iceberg: how a 'low-key' study in England needed 89 professionals to approve it and how we can do better" Petrova and Barclay highlight concerns with the health research regulatory environment in the UK. DISCUSSION: As long-standing chairs of NHS research ethics committees, researchers, and also academics in research ethics, we are also often frustrated with the regulatory process in the UK. However, we think that Petrova and Barclay's analysis is misleading because it conflates research ethics with governance and funding processes, thus failing to adequately distinguish between the national coordinating function of the Health Research Authority, local research governance processes, and interactions with research sponsors and/or the Clinical Research Network.

Radiation resistant fiber Bragg grating in random air-line fibers for sensing applications in nuclear reactor cores.

This paper reports the testing results of radiation resistant fiber Bragg grating (FBG) in random air-line (RAL) fibers in comparison with FBGs in other radiation-hardened fibers. FBGs in RAL fibers were fabricated by 80 fs ultrafast laser pulse using a phase mask approach. The fiber Bragg gratings tests were carried out in the core region of a 6 MW MIT research reactor (MITR) at a steady temperature above 600°C and an average fast neutron (>1 MeV) flux >1.2 × 1014 n/cm2/s. Fifty five-day tests of FBG sensors showed less than 5 dB reduction in FBG peak strength after over 1 × 1020 n/cm2 of accumulated fast neutron dose. The radiation-induced compaction of FBG sensors produced less than 5.5 nm FBG wavelength shift toward shorter wavelength. To test temporal responses of FBG sensors, a number of reactor anomaly events were artificially created to abruptly change reactor power, temperature, and neutron flux over short periods of time. The thermal sensitivity and temporal responses of FBGs were determined at different accumulated doses of neutron flux. Results presented in this paper reveal that temperature-stable Type-II FBGs fabricated in radiation-hardened fibers can survive harsh in-pile conditions. Despite large parameter drift induced by strong nuclear radiation, further engineering and innovation on both optical fibers and fiber devices could lead to useful fiber sensors for various in-pile measurements to improve safety and efficiency of existing and next generation nuclear reactors.

Persistent organic pollutants as predictors of increased FSH:LH ratio in naturally cycling, reproductive age women.

Although several recent studies suggest endocrine disrupting compounds, such as polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (p,p', DDE), and hexachlorobenzene (HCB), target different organs and systems in the body, their impact on female reproductive function in humans is not well characterized. We seek to determine the relationship between several known endocrine disrupting compounds and a marker of ovarian responsivity, the FSH:LH ratio (higher ratio indicates less ovarian responsivity). For this analysis, 169 naturally cycling women between 21 and 38 years of age completed interviews and had their blood drawn on day 3 of their menstrual cycle for analyses of toxicants, gonadal sex hormones (E2 and P4), and gonadotropins (FSH and LH). PCB congeners were classified into five groups based on their environmental persistence, distribution in human tissue, and toxicological action, reflecting the structure, mechanism, and known biological activity of individual PCB congeners. For every unit (ppb) increase in the level of the estrogenic PCB group, there was a 5-fold greater risk of a FSH:LH ratio ≥ 2, controlling for individual differences in age, percent body fat, cycle day 3 estradiol levels, parity, alcohol use and cigarette smoking in the past year (exp[ß] = 5; p = ≤0.01). PCB congeners identified as estrogenic were analyzed individually, and, of the 19 potentially estrogenic congeners, five were significantly, and positively related to an increased FSH:LH ratio. Four of these congeners are non-persistent, easily volatilize in the environment, and are easily metabolized, and hence, are indicative of very recent or current exposure. p,p'-DDE and HCB were not associated with FSH:LH ratio. We find a clinical indicator of ovarian responsivity, FSH:LH ratio, is associated with a specific group of estrogenic PCBs. These congeners may become airborne when they volatilize from dredged PCB-contaminated soil or from indoor PCB-containing window caulk and sealants in older buildings leading to inhalation exposure. PCB exposure, particularly to non-persistent, estrogenic congeners, may pose an unrecognized threat to female fecundity within the general population.

Exposure to perfluoroalkyl substances and associations with serum thyroid hormones in a remote population of Alaska Natives.

Perfluoroalkyl substances (PFASs) are known to accumulate in traditional food animals of the Arctic, and arctic indigenous peoples may be exposed via consumption of subsistence-harvested animals. PFASs are suspected of disrupting thyroid hormone homeostasis in humans. The aim of this study is to assess the relationship between serum PFASs and thyroid function in a remote population of Alaska Natives. Serum samples were collected from 85 individuals from St. Lawrence Island, Alaska. The concentrations of 13 PFASs, as well as free and total thyroxine (T4), free and total triiodothyronine (T3), and thyrotropin (TSH) were quantified in serum samples. The relationships between circulating concentrations of PFASs and thyroid hormones were assessed using multiple linear regression fit with generalized estimating equations. Several PFASs, including perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA), were positively associated with TSH concentrations when modeled individually. PFOS and PFNA were significantly associated with free T3 and PFNA was significantly associated with total T3 in models with PFAS*sex interactive terms; these associations suggested negative associations in men and positive associations in women. PFASs were not significantly associated with concentrations of free or total T4. Serum PFASs are associated with circulating thyroid hormone concentrations in a remote population of Alaska Natives. The effects of PFAS exposure on thyroid hormone homeostasis may differ between sexes.