Three-dimensional feedback processes in current-driven metal.

Using three-dimensional (3D) magnetohydrodynamic simulations, we study how a pit on a metal surface evolves when driven by intense electrical current density j. Redistribution of j around the pit initiates a feedback loop: j both reacts to and alters the electrical conductivity σ, through Joule heating and hydrodynamic expansion, so that j and σ are constantly in flux. Thus, the pit transforms into larger striation and filament structures predicted by the electrothermal instability theory. Both structures are important in applications of current-driven metal: The striation constitutes a density perturbation that can seed the magneto-Rayleigh-Taylor instability, while the filament provides a more rapid path to plasma formation, through 3D j redistribution. Simulations predict distinctive self-emission patterns, thus allowing for experimental observation and comparison.

Seeding the Electrothermal Instability through a Three-Dimensional, Nonlinear Perturbation.

Electrothermal instability plays an important role in applications of current-driven metal, creating striations (which seed the magneto-Rayleigh-Taylor instability) and filaments (which provide a more rapid path to plasma formation). However, the initial formation of both structures is not well understood. Simulations show for the first time how a commonly occurring isolated defect transforms into the larger striation and filament, through a feedback loop connecting current and electrical conductivity. Simulations have been experimentally validated using defect-driven self-emission patterns.

Minimally Invasive Cubital Tunnel Release Utilizing Lighted Retractors: A Study of Residents Novel to this Technique Utilizing a Cadaveric Model.

The purpose of this study was to evaluate whether a minimally-invasive cubital tunnel release using lighted retractors could be performed safely and completely by residents with no prior training in this technique. Ten residents participated in the study. Postoperative dissection of the specimens was performed utilizing a detailed checklist and global rating scale to evaluate the completeness of release as well as presence of neurologic injury. Performance of residents was compared. Rho correlation analysis was used to verify validity of the assessment tools. Training year most strongly correlated with Global Rating Scale assessment values. There was a trend correlating training year with faster surgical times, and Detailed Checklist scores. Validation measurements showed strong correlations between the pass/fail grade and the Detailed Checklist and the Global Rating Scale. Complete release of the ulnar nerve in situ utilizing lighted retractors can be performed with minimal training or experience. (Journal of Surgical Orthopaedic Advances 32(3):193-198, 2023).

THYROID SCREENING AND RELIABILITY OF RADIATION THYROID DOSES FOR THE BELARUSIAN IN UTERO COHORT.

OBJECTIVE: To describe the status and results of thyroid disease screening and assessment of reliability of radiationthyroid doses in the Belarusian in utero cohort of 2,965 individuals exposed to Chernobyl (Chornobyl) fallout. MATERIALS AND METHODS: Thyroid screening examinations are currently underway including thyroid palpation by anendocrinologist, ultrasonographic examination by an ultrasonographer and analysis of blood samples for diagnosisof hypo- and hyperthyroidism, autoimmune thyroiditis, thyroid function tests (thyroid-stimulating hormone [TSH],thyroxine [T4], thyroid peroxidase antibody [anti-TPO], and thyroglobulin antibodies [anti-TG]). Reliability of (i)information from 780 pairs of questionnaires obtained during the first and second interviews of the mothers and (ii)thyroid doses, which were calculated for the cohort members using this information, is evaluated. RESULTS: As of 15 August 2021, 1,267 in utero exposed study subjects had been screened. A single thyroid nodule wasdiagnosed in 167 persons (13.2 % of the total) and multiple thyroid nodules in 101 persons (8.0 %): 189 (14.9 %)persons had nodules detected for the first time at the screening while 79 (6.2 %) persons had nodules detected pre-viously (pre-screening nodules). Fifty-nine out of 268 subjects (22.0 %) with a suspicious thyroid nodule werereferred to fine needle aspiration biopsy, and among them 33 (55.9 %) were biopsied. Reasonable agreement wasobserved for modelqbased doses calculated for the Belarusian in utero cohort members using data from the two inter-views (Spearman's rank-correlation coefficient rs = 0.74, p < 0.001), while measurementqbased doses yielded almost per-fect agreement (rs = 0.99, p < 0.001). CONCLUSIONS: During the thyroid screening, at least one thyroid nodule was identified in 268 of 1,267 (21.2 %) inutero exposed cohort members. Seven thyroid cancer cases were identified in the cohort, including 5 pre-screeningcases and 2 cases detected during the screening. Ongoing research on this unique cohort will provide importantinformation on adverse health effects following prenatal and postnatal exposure to radioiodine and radiocesium iso-topes, for which available epidemiological data are scant.

A Review of Guselkumab, an IL-23 Inhibitor, for Moderate-to-Severe Plaque Psoriasis.

Psoriasis is a chronic inflammatory skin disorder that affects 2% of the population. Evidence suggests that interleukin (IL)-23 plays a pivotal role in the pathogenesis of psoriasis. Guselkumab is a subcutaneously administered, humanized anti-IL23 monoclonal antibody indicated for the treatment of moderate-to-severe plaque psoriasis. Data from Phase I-III trials in this patient population reveal that guselkumab has proven to be superior to placebo or adalimumab based on achieving a Psoriasis Area and Severity Index (PASI) 90% reduction, or a static Physician Global Assessment (sPGA) score of 0 or 1 from baseline. This article reviews the current status of guselkumab as a therapy for moderate-to-severe plaque psoriasis.

The cost effectiveness of vancomycin for preventing infections after shoulder arthroplasty: a break-even analysis.

BACKGROUND: Increasing methicillin resistance and recognition of Propionibacterium acnes as a cause of infection in shoulder arthroplasty has led to the adoption of local vancomycin powder application as a more effective method to prevent expensive periprosthetic infections. However, no study has analyzed the cost effectiveness of vancomycin powder for preventing infection after shoulder replacement. METHODS: Cost data for infection-related care of 16 patients treated for deep periprosthetic shoulder infection was collected from our institution for the break-even analysis. An equation was developed and applied to the data to determine how effective vancomycin powder would need to be at reducing a baseline infection rate to make prophylactic use cost effective. RESULTS: The efficacy of vancomycin (absolute risk reduction [ARR]) was evaluated at different unit costs, baseline infection rates, and average costs of treating infection. We determined vancomycin to be cost effective if the initial infection rate decreased by 0.04% (ARR). Using the current costs of vancomycin reported in the literature (range: $2.50/1000 mg to $44/1000 mg), we determined vancomycin to be cost effective with an ARR range of 0.01% at a cost of $2.50/1000 mg to 0.19% at $44/1000 mg. Baseline infection rate does not influence the ARR obtained at any specific cost of vancomycin or the cost of treating infection. CONCLUSIONS: We have derived and used a break-even equation to assess efficacy of prophylactic antibiotics during shoulder surgery. We further demonstrated the prophylactic administration of local vancomycin powder during shoulder arthroplasty to be a highly cost-effective practice.

Non-radiation risk factors for leukemia: A case-control study among chornobyl cleanup workers in Ukraine.

BACKGROUND: Occupational and environmental exposure to chemicals such as benzene has been linked to increased risk of leukemia. Cigarette smoking and alcohol consumption have also been found to affect leukemia risk. Previous analyses in a large cohort of Chornobyl clean-up workers in Ukraine found significant radiation-related increased risk for all leukemia types. We investigated the potential for additional effects of occupational and lifestyle factors on leukemia risk in this radiation-exposed cohort. METHODS: In a case-control study of chronic lymphocytic and other leukemias among Chornobyl cleanup workers, we collected data on a range of non-radiation exposures. We evaluated these and other potential risk factors in analyses adjusting for estimated bone marrow radiation dose. We calculated Odds Ratios and 95% Confidence Intervals in relation to lifestyle factors and occupational hazards. RESULTS: After adjusting for radiation, we found no clear association of leukemia risk with smoking or alcohol but identified a two-fold elevated risk for non-CLL leukemia with occupational exposure to petroleum (OR=2.28; 95% Confidence Interval 1.13, 6.79). Risks were particularly high for myeloid leukemias. No associations with risk factors other than radiation were found for chronic lymphocytic leukemia. CONCLUSIONS: These data - the first from a working population in Ukraine - add to evidence from several previous reports of excess leukemia morbidity in groups exposed environmentally or occupationally to petroleum or its products.

Non-thyroid cancer in Northern Ukraine in the post-Chernobyl period: Short report.

The Chernobyl nuclear power plant accident in Ukraine in 1986 led to widespread radioactive releases into the environment - primarily of radioiodines and cesium - heavily affecting the northern portions of the country, with settlement-averaged thyroid doses estimated to range from 10 mGy to more than 10 Gy. The increased risk of thyroid cancer among exposed children and adolescents is well established but the impact of radioactive contamination on the risk of other types of cancer is much less certain. To provide data on a public health issue of major importance, we have analyzed the incidence of non-thyroid cancers during the post-Chernobyl period in a well-defined cohort of 13,203 individuals who were <18 years of age at the time of the accident. The report is based on standardized incidence ratio (SIR) analysis of 43 non-thyroid cancers identified through linkage with the National Cancer Registry of Ukraine for the period 1998 through 2009. We compared the observed and expected number of cases in three cancer groupings: all solid cancers excluding thyroid, leukemia, and lymphoma. Our analyses found no evidence of a statistically significant elevation in cancer risks in this cohort exposed at radiosensitive ages, although the cancer trends, particularly for leukemia (SIR=1.92, 95% confidence interval: 0.69; 4.13), should continue to be monitored.

Iodine-131 dose-dependent gene expression: alterations in both normal and tumour thyroid tissues of post-Chernobyl thyroid cancers.

BACKGROUND: A strong, consistent association between childhood irradiation and subsequent thyroid cancer provides an excellent model for studying radiation carcinogenesis. METHODS: We evaluated gene expression in 63 paired RNA specimens from frozen normal and tumour thyroid tissues with individual iodine-131 (I-131) doses (0.008-8.6 Gy, no unirradiated controls) received from Chernobyl fallout during childhood (Ukrainian-American cohort). Approximately half of these randomly selected samples (32 tumour/normal tissue RNA specimens) were hybridised on 64 whole-genome microarrays (Agilent, 4 × 44 K). Associations between I-131 dose and gene expression were assessed separately in normal and tumour tissues using Kruskal-Wallis and linear trend tests. Of 155 genes significantly associated with I-131 after Bonferroni correction and with ≥2-fold increase per dose category, we selected 95 genes. On the remaining 31 RNA samples these genes were used for validation purposes using qRT-PCR. RESULTS: Expression of eight genes (ABCC3, C1orf9, C6orf62, FGFR1OP2, HEY2, NDOR1, STAT3, and UCP3) in normal tissue and six genes (ANKRD46, CD47, HNRNPH1, NDOR1, SCEL, and SERPINA1) in tumour tissue was significantly associated with I-131. PANTHER/DAVID pathway analyses demonstrated significant over-representation of genes coding for nucleic acid binding in normal and tumour tissues, and for p53, EGF, and FGF signalling pathways in tumour tissue. CONCLUSION: The multistep process of radiation carcinogenesis begins in histologically normal thyroid tissue and may involve dose-dependent gene expression changes.

Estimation of the thyroid doses for ukrainian children exposed in utero after the chernobyl accident.

This paper describes methods for estimating thyroid doses to Ukrainian children who were subjects of an epidemiological study of prenatal exposure and presents the calculated doses. Participants were 2,582 mother-child pairs in which the mother had been pregnant at the time of the Chernobyl accident on 26 April 1986 or in the 2-3 mo following when (131)I in fallout was still present. Among these, 1,494 were categorized as "exposed;" a comparison group of 1,088 was considered "relatively unexposed." Individual in utero thyroid dose estimates were found to range from less than 1 mGy to 3,200 mGy, with an arithmetic mean of 72 mGy. Thyroid doses varied primarily according to stage of pregnancy at the time of exposure and level of radioactive contamination at the location of residence. There was a marked difference between the dose distributions of the exposed and comparison groups, although nine children in the latter group had calculated doses in the range 100-200 mGy. For those children who were born after the accident and prior to the end of June 1986, postnatal thyroid doses were also estimated. About 7.7% (200) of the subjects received thyroid doses after birth that were at least 10% of their cumulative doses.

The Chernobyl accident--an epidemiological perspective.

Twenty-five years have passed since radioactive releases from the Chernobyl nuclear accident led to the exposure of millions of people in Europe. Studies of affected populations have provided important new data on the links between radiation and cancer-particularly the risk of thyroid tumours from exposure to iodine isotopes-that are important not only for a fuller scientific understanding of radiation effects, but also for radiation protection. It is now well documented that children and adolescents exposed to radioiodines from Chernobyl fallout have a sizeable dose-related increase in thyroid cancer, with the risk greatest in those youngest at exposure and with a suggestion that deficiency in stable iodine may increase the risk. Data on thyroid cancer risks to other age groups are somewhat less definitive. In addition, there have been reported increases in incidence and mortality from non-thyroid cancers and non-cancer end points. Although some studies are difficult to interpret because of methodological limitations, recent investigations of Chernobyl clean-up workers ('liquidators') have provided evidence of increased risks of leukaemia and other haematological malignancies and of cataracts, and suggestions of an increase in the risk of cardiovascular diseases, following low doses and low dose rates of radiation. Further careful follow-up of these populations, including the establishment and long-term support of life-span study cohorts, could provide additional important information for the quantification of radiation risks and the protection of persons exposed to low doses of radiation.

Thyroid cancer risk in Belarus among children and adolescents exposed to radioiodine after the Chornobyl accident.

BACKGROUND: Previous studies showed an increased risk of thyroid cancer among children and adolescents exposed to radioactive iodines released after the Chornobyl (Chernobyl) accident, but the effects of screening, iodine deficiency, age at exposure and other factors on the dose-response are poorly understood. METHODS: We screened 11 970 individuals in Belarus aged 18 years or younger at the time of the accident who had estimated (131)I thyroid doses based on individual thyroid activity measurements and dosimetric data from questionnaires. The excess odds ratio per gray (EOR/Gy) was modelled using linear and linear-exponential functions. RESULTS: For thyroid doses <5 Gy, the dose-response was linear (n=85; EOR/Gy=2.15, 95% confidence interval: 0.81-5.47), but at higher doses the excess risk fell. The EOR/Gy was significantly increased among those with prior or screening-detected diffuse goiter, and larger for men than women, and for persons exposed before age 5 than those exposed between 5 and 18 years, although not statistically significant. A somewhat higher EOR/Gy was estimated for validated pre-screening cases. CONCLUSION: 10-15 years after the Chornobyl accident, thyroid cancer risk was significantly increased among individuals exposed to fallout as children or adolescents, but the risk appeared to be lower than in other Chornobyl studies and studies of childhood external irradiation.

Prevalence of hyperthyroidism after exposure during childhood or adolescence to radioiodines from the chornobyl nuclear accident: dose-response results from the Ukrainian-American Cohort Study.

Relatively few data are available on the prevalence of hyperthyroidism (TSH concentrations of <0.3 mIU/liter, with normal or elevated concentrations of free T4) in individuals exposed to radioiodines at low levels. The accident at the Chornobyl (Chernobyl) nuclear plant in Ukraine on April 26, 1986 exposed large numbers of residents to radioactive fallout, principally to iodine-131 ((131)I) (mean and median doses  =  0.6 Gy and 0.2 Gy). We investigated the relationship between (131)I and prevalent hyperthyroidism among 11,853 individuals exposed as children or adolescents in Ukraine who underwent an in-depth, standardized thyroid gland screening examination 12-14 years later. Radioactivity measurements taken shortly after the accident were available for all subjects and were used to estimate individual thyroid doses. We identified 76 cases of hyperthyroidism (11 overt, 65 subclinical). Using logistic regression, we tested a variety of continuous risk models and conducted categorical analyses for all subjects combined and for females (53 cases, n  =  5,767) and males (23 cases, n  =  6,086) separately but found no convincing evidence of a dose-response relationship between (131)I and hyperthyroidism. There was some suggestion of elevated risk among females in an analysis based on a dichotomous dose model with a threshold of 0.5 Gy chosen empirically (OR  =  1.86, P  =  0.06), but the statistical significance level was reduced (P  =  0.13) in a formal analysis with an estimated threshold. In summary, after a thorough exploration of the data, we found no statistically significant dose-response relationship between individual (131)I thyroid doses and prevalent hyperthyroidism.

A screening study of thyroid cancer and other thyroid diseases among individuals exposed in utero to iodine-131 from Chernobyl fallout.

BACKGROUND: Like stable iodine, radioiodines concentrate in the thyroid gland, increasing thyroid cancer risk in exposed children. Data on exposure to the embryonic/fetal thyroid are rare, raising questions about use of iodine 131 (I-131) in pregnant women. We present here estimated risks of thyroid disease from exposure in utero to I-131 fallout from the Chernobyl nuclear accident. METHODS: We conducted a cross-sectional thyroid screening study (palpation, ultrasound, thyroid hormones, and, if indicated, fine needle aspiration) from 2003 to 2006. Participants were 2582 mother-child pairs from Ukraine in which the mother had been pregnant at the time of the accident on April 26, 1986, or 2 months after the time during which I-131 fallout was still present (1494 from contaminated areas, 1088 in the comparison group). Individual cumulative in utero thyroid dose estimates were derived from estimated I-131 activity in the mother's thyroid (mean 72 mGy; range 0-3230 mGy). RESULTS: There were seven cases of thyroid carcinoma and one case of Hurthle cell neoplasm identified as a result of the screening. Whereas the estimated excess odds ratio per gray for thyroid carcinoma was elevated (excess odds ratio per gray 11.66), it was not statistically significant (P = 0.12). No radiation risks were identified for other thyroid diseases. CONCLUSION: Our results suggest that in utero exposure to radioiodines may have increased the risk of thyroid carcinoma approximately 20 yr after the Chernobyl accident, supporting a conservative approach to medical uses of I-131 during pregnancy.

The Ukrainian-American study of leukemia and related disorders among Chornobyl cleanup workers from Ukraine: I. Study methods.

There are relatively few data on the risk of leukemia among those exposed to external radiation during cleanup operations after the Chornobyl nuclear accident, and results have not been consistent. To investigate this further, we assembled a cohort of 110,645 male cleanup workers from Ukraine and identified cases of leukemia occurring during the period 1986 to 2000. Detailed interviews were conducted and individual bone marrow doses estimated using a new time-and-motion method known as RADRUE described in companion paper II. For the initial analyses we used a nested case-control approach with a minimum of five controls per case, matched for year of birth, oblast (region) of registration, and residence. All identified cases were reviewed by an international panel of experts; 87 of 111 were confirmed. The dose-response analysis and results are given in companion paper III. As background, we describe herein the design, procedures, outcome of case finding and confirmation, control selection, dose estimation and interviewing of subjects.

Autoimmune thyroiditis and exposure to iodine 131 in the Ukrainian cohort study of thyroid cancer and other thyroid diseases after the Chornobyl accident: results from the first screening cycle (1998-2000).

CONTEXT: Due to the Chornobyl accident, millions were exposed to radioactive isotopes of iodine and some received appreciable iodine 131 (131I) doses. A subsequent increase in thyroid cancer has been largely attributed to this exposure, but evidence concerning autoimmune thyroiditis (AIT) remains inconclusive. OBJECTIVE: The objective of the study was to quantify risk of AIT after 131I exposure. DESIGN/SETTING/PARTICIPANTS: Baseline data were collected from the first screening cycle (1998-2000) of a large cohort of radiation-exposed individuals (n = 12,240), residents of contaminated, iodine-deficient territories of Ukraine. Study individuals were under the age of 18 yr on April 26, 1986, and had thyroid radioactivity measurements made shortly after the accident. OUTCOMES: AIT was defined a priori based on various combinations of elevated antibodies to thyroid peroxidase (ATPO), TSH, and clinical findings; elevated ATPO were considered to be an indicator of thyroid autoimmunity. RESULTS: No significant association was found between 131I thyroid dose estimates and AIT, but prevalence of elevated ATPO demonstrated a modest, significant association with 131I that was well described by several concave models. This relationship was apparent in individuals with moderately elevated ATPO and euthyroid, thyroid disease-free individuals. CONCLUSIONS: Twelve to 14 yr after the Chornobyl accident, no radiation-related increase in prevalence of AIT was found in a large cohort study, the first in which 131I thyroid doses were estimated using individual radioactivity measurements. However, a dose-response relationship with ATPO prevalence raises the possibility that clinically important changes may occur over time. Thus, further follow-up and analysis of prospective data in this cohort are necessary.

Oxalobacter sp. reduces urinary oxalate excretion by promoting enteric oxalate secretion.

The primary goal of this study was to test the hypothesis that Oxalobacter colonization alters colonic oxalate transport thereby reducing urinary oxalate excretion. In addition, we examined the effects of intraluminal calcium on Oxalobacter colonization and tested the hypothesis that endogenously derived colonic oxalate could be degraded by lyophilized Oxalobacter enzymes targeted to this segment of the alimentary tract. Oxalate fluxes were measured across short-circuited, in vitro preparations of proximal and distal colon removed from Sprague-Dawley rats and placed in Ussing chambers. For these studies, rats were colonized with Oxalobacter either artificially or naturally, and urinary oxalate, creatinine and calcium excretions were determined. Colonized rats placed on various dietary treatment regimens were used to evaluate the impact of calcium on Oxalobacter colonization and whether exogenous or endogenous oxalate influenced colonization. Hyperoxaluric rats with some degree of renal insufficiency were also used to determine the effects of administering encapsulated Oxalobacter lysate on colonic oxalate transport and urinary oxalate excretion. We conclude that in addition to its intraluminal oxalate-degrading capacity, Oxalobacter interacts physiologically with colonic mucosa by inducing enteric oxalate secretion/excretion leading to reduced urinary excretion. Whether Oxalobacter, or products of Oxalobacter, can therapeutically reduce urinary oxalate excretion and influence stone disease warrants further investigation in long-term studies in various patient populations.

Iodine excretion in regions of Ukraine affected by the Chornobyl Accident: experience of the Ukrainian-American cohort study of thyroid cancer and other thyroid diseases.

Urinary iodine concentrations were measured in 11,926 subjects who are participants in the Ukrainian-American Cohort Study of Thyroid Cancer and Other Thyroid Diseases Following the Chornobyl Accident. Measurements were made in two time periods corresponding to the first and second thyroid screening cycles (1998-2000, 2001-2003). These time periods fall before and after initiation of a government program to increase iodine sufficiency. Median urinary iodine concentrations did increase in the later time period compared to the earlier [47.5 microg/L, 95% confidence interval (CI) 46.5-48.9 microg/L versus 41.7 microg/L, 95% CI 40.4-42.5 microg/L], but levels remained in the mild-to-moderate iodine deficiency range as defined by the World Health Organization (WHO), indicating the need for further efforts at iodination. In both time periods, urinary iodine levels were found to vary by place of residence and were lower in rural compared to urban areas. Iodine status needs to be considered when evaluating risk of thyroid cancer and other thyroid diseases.