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INTRODUCTION/AIMS: Not all patients with chronic inflammatory demyelinating polyneuropathy (CIDP) have evidence of demyelination on nerve conduction studies (NCS). Patients with "supportive" evidence of CIDP on cerebrospinal fluid (CSF), magnetic resonance imaging (MRI), ultrasound (US), or nerve biopsy but not on NCS, often receive immunomodulating therapy. We evaluated the treatment response of patients with clinical and supportive features of CIDP lacking NCS evidence of demyelination. METHODS: Retrospective chart review was conducted on 232 patients who met CIDP clinical criteria and were treated with disease-modifying therapy. Patients included did not have NCS criteria of demyelination, but did have supportive CSF, MRI, or US findings consistent with CIDP. A positive treatment response was defined as at least a one-point improvement in the modified Rankin scale (mRS), or a four-point increase in the Medical Research Council sum score (MRCSS). RESULTS: Twenty patients met criteria: 17 of the 18 (94%) patients with CSF protein >45 mg/dL, 6 of the 14 (43%) with MRI lumbosacral root or plexus enhancement, and 4 of the 6 (67%) with enlarged proximal nerves on US. Eighteen patients received intravenous immunoglobulin, 10 corticosteroids, one plasma exchange, and six other immunomodulatory therapies. Twelve patients had a positive treatment response on the MRCSS or mRS. The presence of MRI lumbosacral root or plexus enhancement was associated with a positive treatment response. DISCUSSION: A trial of immunomodulating treatment should be considered for patients with clinical features of CIDP in the absence of NCS evidence of demyelination, particularly when there is MRI lumbosacral root or plexus enhancement.

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CONTEXT: Interscholastic heat policies for football have not been evidence based. Therefore, their effectiveness in mitigating exertional heat illness has not been assessed. OBJECTIVE: To discuss the development of the Georgia High School Association heat policy and assess the effectiveness of revised guidelines. DESIGN: Descriptive epidemiology study. SETTING: Georgia high schools. PATIENTS OR OTHER PARTICIPANTS: Interscholastic football players in grades 9 through 12. MAIN OUTCOME MEASURE(S): Heat syncope and heat exhaustion (HS/HE) illness rates (IRs) were calculated per 1000 athlete-exposures (AEs), and relative risk (RR) was calculated as a ratio of postpolicy (POST) IR divided by prepolicy (PRE) IR. RESULTS: A total of 214 HS/HE cases (172 PRE, 42 POST) and 341 348 AEs (178 230 PRE, 163 118 POST) were identified. During the first 5 days of the PRE period, approximately 50% of HS/HE illnesses occurred; HS/HE IRs doubled when practice sessions increased from 2 to 2.5 hours and tripled for practices ≥3 hours. The HS/HE IRs in the PRE period increased from 0.44/1000 AEs for wet-bulb globe temperatures (WBGTs) of <82°F (<27.8°C) to >2.0/1000 AEs for WBGTs from 87°F (30.6°C) to 89.9°F (32.2°C). The RRs comparing PRE and POST policy periods were 0.29 for WBGTs of <82.0°F (<27.80°C), 0.65 for WBGTs from 82.0°F (27.8°C) to 86.9°F (30.5°C), and 0.23 for WBGTs from 87.0°F (30.6°C) to 89.9°F (32.2°C). No HS/HE illnesses occurred in the POST period for WBGTs at >90°F (>32.3°C). CONCLUSIONS: Results from the PRE period guided the Georgia High School Association to revise its heat and humidity policy to include a mandated 5-day acclimatization period when no practices may exceed 2 hours and the use of WBGT-based activity-modification categories. The new policy reduced HS/HE IRs by 35% to 100%, depending on the WBGT category. Our results may be generalizable to other states with hot and humid climates similar to that of Georgia.

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The number of online data repositories is growing and they are becoming increasingly difficult to navigate. Data are scattered among different repositories, or hidden on personal or institutional servers. To access data, users must search extensively and rely on site-specific tools. These hurdles substantially inhibit data findability and accessibility; in particular, those in the long tail of data. We developed an open source web application, Spatial Data Hub, that is a geospatial data index, connected to remote Internet sources. It allows simultaneous display and comparison of disparate datasets on a single map. It aims to promote all data equally and provide the flexibility to connect to any storage system, effectively making long-tail datasets as visible as those in large, established repositories. Its low barrier of entry allows scientists and organizations to easily add data throughout the research process; enhancing transparency, openness and reproducibility. This flexibility and functionality makes Spatial Data Hub a novel platform for researchers to promote their work, develop new hypotheses and create new collaborations.

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Angiostrongylus cantonensis (rat lungworm), a parasitic nematode, is expanding its distribution. Human infection, known as angiostrongyliasis, may manifest as eosinophilic meningitis, an emerging infectious disease. The range and incidence of this disease are expanding throughout the tropics and subtropics. Recently, the Hawaiian Islands have experienced an increase in reported cases. This study addresses factors affecting the parasite's distribution and projects its potential future distribution, using Hawaii as a model for its global expansion. Specimens of 37 snail species from the Hawaiian Islands were screened for the parasite using PCR. It was present on five of the six largest islands. The data were used to generate habitat suitability models for A. cantonensis, based on temperature and precipitation, to predict its potential further spread within the archipelago. The best current climate model predicted suitable habitat on all islands, with greater suitability in regions with higher precipitation and temperatures. Projections under climate change (to 2100) indicated increased suitability in regions with estimated increased precipitation and temperatures, suitable habitat occurring increasingly at higher elevations. Analogously, climate change could facilitate the spread of A. cantonensis from its current tropical/subtropical range into more temperate regions of the world, as is beginning to be seen in the continental USA.

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CONTEXT: Wet bulb globe temperature (WBGT) is the gold standard for assessing environmental heat stress during physical activity. Many manufacturers of commercially available instruments fail to report WBGT accuracy. OBJECTIVE: To determine the accuracy of several commercially available WBGT monitors compared with a standardized reference device. DESIGN: Observational study. SETTING: Field test. PATIENTS OR OTHER PARTICIPANTS: Six commercially available WBGT devices. MAIN OUTCOME MEASURE(S): Data were recorded for 3 sessions (1 in the morning and 2 in the afternoon) at 2-minute intervals for at least 2 hours. Mean absolute error (MAE), root mean square error (RMSE), mean bias error (MBE), and the Pearson correlation coefficient ( r) were calculated to determine instrument performance compared with the reference unit. RESULTS: The QUESTemp° 34 (MAE = 0.24°C, RMSE = 0.44°C, MBE = -0.64%) and Extech HT30 Heat Stress Wet Bulb Globe Temperature Meter (Extech; MAE = 0.61°C, RMSE = 0.79°C, MBE = 0.44%) demonstrated the least error in relation to the reference standard, whereas the General WBGT8778 Heat Index Checker (General; MAE = 1.18°C, RMSE = 1.34°C, MBE = 4.25%) performed the poorest. The QUESTemp° 34 and Kestrel 4400 Heat Stress Tracker units provided conservative measurements that slightly overestimated the WBGT provided by the reference unit. Finally, instruments using the psychrometric wet bulb temperature (General, REED Heat Index WBGT Meter, and WBGT-103 Heat Stroke Checker) tended to underestimate the WBGT, and the resulting values more frequently fell into WBGT-based activity categories with fewer restrictions as defined by the American College of Sports Medicine. CONCLUSIONS: The QUESTemp° 34, followed by the Extech, had the smallest error compared with the reference unit. Moreover, the QUESTemp° 34, Extech, and Kestrel units appeared to offer conservative yet accurate assessments of the WBGT, potentially minimizing the risk of allowing physical activity to continue in stressful heat environments. Instruments using the psychrometric wet bulb temperature tended to underestimate WBGT under low wind-speed conditions. Accurate WBGT interpretations are important to enable clinicians to guide activities in hot and humid weather conditions.

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Surgical site infections (SSIs) have always complicated recovery after surgery, being associated with increased cost of hospitalization, length of stay, and mortality. The most significant measure to reduce the incidence of SSI was the standardization of prophylactic antibiotic administration in patients undergoing surgical procedures. Since then, countless measures have been proposed to improve rates of SSI and patient outcome, but few have been as efficacious as prophylactic antibiotics. Therefore, SSI continues to plague clinicians and patients in modern health care. This review focuses on current and future efforts at SSI control.

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As an exclusively human pathogen, Streptococcus pyogenes (the group A streptococcus [GAS]) has specifically adapted to evade host innate immunity and survive in multiple tissue niches, including blood. GAS can overcome the metabolic constraints of the blood environment and expresses various immunomodulatory factors necessary for survival and immune cell resistance. Here we present our investigation of one such factor, the predicted LysR family transcriptional regulator CpsY. The encoding gene, cpsY, was initially identified as being required for GAS survival in a transposon-site hybridization (TraSH) screen in whole human blood. CpsY is homologous with transcriptional regulators of Streptococcus mutans (MetR), Streptococcus iniae (CpsY), and Streptococcus agalactiae (MtaR) that regulate methionine transport, amino acid metabolism, resistance to neutrophil-mediated killing, and survival in vivo Our investigation indicated that CpsY is involved in GAS resistance to innate immune cells of its human host. However, GAS CpsY does not manifest the in vitro phenotypes of its homologs in other streptococcal species. GAS CpsY appears to regulate a small set of genes that is markedly different from the regulons of its homologs. The differential expression of these genes depends on the growth medium, and CpsY modestly influences their expression. The GAS CpsY regulon includes known virulence factors (mntE, speB, spd, nga [spn], prtS [SpyCEP], and sse) and cell surface-associated factors of GAS (emm1, mur1.2, sibA [cdhA], and M5005_Spy0500). Intriguingly, the loss of CpsY in GAS does not result in virulence defects in murine models of infection, suggesting that CpsY function in immune evasion is specific to the human host.

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BACKGROUND: A key question in care of patients with chronic hepatitis C virus (HCV) infection is beginning treatment immediately vs delaying treatment. Risks of mortality and disease progression in "real world" settings are important to assess the implications of delaying HCV treatment. METHODS: This was a cohort study of HCV patients identified from 4 integrated health systems in the United States who had liver biopsies during 2001-2012. The probabilities of death and progression to hepatocellular carcinoma, hepatic decompensation (hepatic encephalopathy, esophageal varices, ascites, or portal hypertension) or liver transplant were estimated over 1, 2, or 5 years by fibrosis stage (Metavir F0-F4) determined by biopsy at beginning of observation. RESULTS: Among 2799 HCV-monoinfected patients who had a qualifying liver biopsy, the mean age at the time of biopsy was 50.7 years. The majority were male (58.9%) and non-Hispanic white (66.9%). Over a mean observation of 5.0 years, 261 (9.3%) patients died and 34 (1.2%) received liver transplants. At 5 years after biopsy, the estimated risk of progression to hepatic decompensation or hepatocellular carcinoma was 37.2% in stage F4, 19.6% in F3, 4.7% in F2, and 2.3% in F0-F1 patients. Baseline biopsy stage F3 or F4 and platelet count below normal were the strongest predictors of progression to hepatic decompensation or hepatocellular carcinoma. CONCLUSIONS: The risks of death and progression to liver failure varied greatly by fibrosis stage. Clinicians and policy makers could use these progression risk data in prioritization and in determining the timing of treatment for patients in early stages of liver disease.

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Streptococcus pyogenes (Group A Streptococcus, GAS) remains a major public health burden worldwide, infecting over 750 million people leading to over 500,000 deaths annually. GAS pathogenesis is complex, involving genetically distinct GAS strains and multiple infection sites. To overcome fastidious genetic manipulations and accelerate pathogenesis investigations in GAS, we developed a mariner-based system (Krmit) for en masse monitoring of complex mutant pools by transposon sequencing (Tn-seq). Highly saturated transposant libraries (Krmit insertions in ca. every 25 nucleotides) were generated in two distinct GAS clinical isolates, a serotype M1T1 invasive strain 5448 and a nephritogenic serotype M49 strain NZ131, and analyzed using a Bayesian statistical model to predict GAS essential genes, identifying sets of 227 and 241 of those genes in 5448 and NZ131, respectively. A large proportion of GAS essential genes corresponded to key cellular processes and metabolic pathways, and 177 were found conserved within the GAS core genome established from 20 available GAS genomes. Selected essential genes were validated using conditional-expression mutants. Finally, comparison to previous essentiality analyses in S. sanguinis and S. pneumoniae revealed significant overlaps, providing valuable insights for the development of new antimicrobials to treat infections by GAS and other pathogenic streptococci.

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STUDY DESIGN: Subgroup analysis of a prospective, randomized database. SUMMARY OF BACKGROUND DATA: Reoperation due to recurrence of index level pathology or adjacent segment disease is a common clinical problem. Despite multiple studies on the incidence of reoperation, there have been few comparative studies establishing risk factors for reoperation after spinal stenosis surgery. The hypothesis of this subgroup analysis was that lumbar fusion or particular patient characteristics, such as obesity, would render patients with lumbar stenosis more susceptible to reoperation at the index or adjacent levels. METHODS: The study population combined the randomized and observational cohorts enrolled in Spine Patient Outcomes Research Trial for treatment of spinal stenosis. The surgically treated patients were stratified according to those who had reoperation (n = 54) or no reoperation (n = 359). Outcome measures were assessed at baseline, 1 year, 2 years, 3 years, and 4 years. The difference in improvement between those who had reoperation and those who did not was determined at each follow-up period. RESULTS: Of the 413 patients who underwent surgical treatment of spinal stenosis, 54 (13%) underwent a reoperation within 4 years. At baseline, there were no significant differences in demographic characteristics or clinical outcome scores between reoperation and nonreoperation groups. Furthermore, between groups there were no differences in the severity of symptoms, obesity, physical examination signs, levels of stenosis, location of stenosis, stenosis severity, levels of fusion, levels of laminectomy, levels decompressed, operation time, and intraoperative or postoperative complications. There was an increased percentage of patients with duration of symptoms greater than 12 months in the reoperation group (56% reoperation vs. 36% no reoperation, P < 0.008). At final follow-up, there was significantly less improvement in the outcome of the reoperation group in MOS 36-item Short-Form Health Survey physical function (14.4 vs. 22.6, P < 0.05), Oswestry Disability Index (-12.4 vs. -21.1, P < 0.01), and Sciatica Bothersomeness Index (-5 vs. -8.1, P < 0.006). CONCLUSION: Lumbar fusion and instrumentation were not associated with increased rate of reoperation at index or adjacent levels compared with nonfusion techniques. The only specific risk factor for reoperation after treatment of spinal stenosis was duration of pretreatment symptoms more than 12 months. The overall incidence of reoperations for spinal stenosis surgery was 13%, and reoperations were equally distributed between index and adjacent lumbar levels. Reoperation may be related to the natural history of spinal degenerative disease.

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BACKGROUND: Venous air embolism is a rare but potentially fatal complication of arthroscopy. Fatal venous air embolism has been reported with as little as 100 mL of air entering the venous system. During liquid-only arthroscopy, avenues for air introduction into the joint are limited. Therefore, we hypothesized that commercially prepared 3-L saline-solution bags are a source of potentially fatal amounts of gas that can be introduced into the joint by arthroscopic pumps. METHODS: Eight 3-L arthroscopic saline-solution bags were obtained and visually inspected for air. The air was aspirated from four bags, and the volume of the air was recorded. A closed-system pump was prepared, and two 3-L bags were connected to it. The pump emptied into an inverted graduated cylinder immersed in a water bath. Both bags were allowed to run dry. Two more bags were then connected and also allowed to run dry. The air was quantified by the downward displacement of water. The experiment was then repeated with the four bags after the air had been aspirated from them. This experiment was performed at three institutions, with utilization of three pump systems and two brands of 3-L saline-solution bags. RESULTS: Air was visualized in all bags, and the bags contained between 34 and 85 mL of air. Arthroscopic pumps can pump air efficiently through the tubing. The total volumes of gas ejected from the tubing after the four 3-L bags had been emptied were 75, 80, and 235 mL. When bags from which the air had been evacuated were used, no air exited the system. CONCLUSIONS: Because a saline-solution arthroscopic pump is theoretically a closed system, venous air embolism has not been a concern. However, this study shows that it is possible to pump a fatal amount of air from 3-L saline-solution bags into an environment susceptible to the creation of emboli. Evacuation of air from the 3-L bags prior to use may eliminate this risk.

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BACKGROUND: The purpose of this article is to review the applications of the extended-dissection technique of the gracilis flap in a high-risk patient population with complex wounds requiring more coverage than a standard gracilis flap may provide. To our knowledge, this is the first study applying the extended-dissection technique as described by Hasen et al. to pedicled gracilis flaps. METHODS: A chart review conducted from 2003 to 2006 identified 19 consecutive patients as having undergone an extended gracilis dissection. Once the pedicle is identified on the medial border of the gracilis, dissection continues proximally, dividing the rich vascular network of perforators to the adductor muscles. The gracilis is then passed beneath the adductor longus and delivered adjacent to the sartorius, where dissection proceeds directly down to the profunda femoris. RESULTS: All reconstructions were successful. There was one complication presenting as a late infection at the donor site. Mean patient age was 66 years and nearly all patients had multiple significant comorbidities, including diabetes, peripheral vascular disease, and/or radiation therapy. CONCLUSIONS: The extended-dissection technique for gracilis harvest has significant benefits for use in pedicled flaps, including a greater arc of rotation and no restriction on postoperative ambulation or thigh abduction. These factors are particularly important in the challenging patient population represented in this study and add to the reliability and versatility of the gracilis flap. Anatomical illustrations for technical guidance in this procedure are also provided.

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Non-clinical studies were conducted to evaluate the toxicity of Antalarmin, a corticotropin-releasing hormone type 1 receptor antagonist being developed for therapy of stress-related pathologies. Antalarmin was not genotoxic in bacterial mutagenesis assays, mammalian cell mutagenesis assays, or in vivo DNA damage assays. In a 14-day range-finding study in rats, Antalarmin doses >or=500 mg/kg/day (3,000 mg/m(2)/day) induced mortality. In a 90-day toxicity study in rats, no gross toxicity was seen at doses of 30, 100, or 300 mg/kg/day (180, 600, or 1,800 mg/m(2)/day, respectively). Antalarmin (300 mg/kg/day) induced mild anemia, increases in serum gamma-glutamyl transferase activity, and microscopic hepatic pathology (bile duct hyperplasia and epithelial necrosis, periportal inflammation). Microscopic renal changes (cortical necrosis, inflammation, hypertrophy, nephropathy) were observed in rats at all Antalarmin doses. In a 14-day range-finding study in dogs, Antalarmin doses >or=50mg/kg/day (1,000 mg/m(2)/day) induced repeated emesis and bone marrow suppression. In a 90-day toxicity study in dogs, Antalarmin (4, 8, or 16 mg/kg/day (80, 160, or 320 mg/m(2)/day, respectively)) induced bone marrow and lymphoid depletion, but no gross toxicity. Comparative in vitro studies using rat, dog, and human neutrophil progenitors demonstrated that canine bone marrow cells are highly sensitive to Antalarmin cytotoxicity, while rat and human bone marrow cells are relatively insensitive. As such, the bone marrow toxicity observed in dogs is considered likely to over-predict Antalarmin toxicity in humans. The hepatic and renal toxicities seen in rats exposed to Antalarmin identify those tissues as the most likely targets for Antalarmin toxicity in humans.

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In this report, results are presented from an international study of the in vitro micronucleus assay using Chinese hamster ovary cells. This study was coordinated by an organizing committee supported by the SFTG (the French branch of the European Environmental Mutagen Society). Test chemicals included mannitol, bleomycin, cytosine arabinoside, urethane and diethylstilboestrol. Mitomycin C was used as a positive control. Each chemical was evaluated in at least two laboratories following a variety of different protocols (short and long exposures, varying recovery times, with and without cytochalasin B) in order to help determine a standard protocol for routine testing in Chinese hamster ovary cells. Mannitol and urethane were negative, while bleomycin, cytosine arabinoside and diethylstilboestrol induced a dose dependent increase in micronucleated cells. In the presence of cytochalasin B, increases in micronuclei were observed in binucleated as well as mononucleated cells in cultures treated with bleomycin, cytosine arabinoside or diethylstilboestrol. Importantly, all three of these chemicals were detected in each of the different treatment/recovery regimens. No differences were seen in the sensitivity or accuracy of the responses in the presence of absence of cytochalasin B. Overall, these results demonstrate the suitability of Chinese hamster ovary cells for the in vitro micronucleus assay.

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Lineaments derived from three image types (1:80,000 black and white, 1:58,000 color infrared, and 1:250,000 side-looking airborne radar) were compared to water-bearing features within a 9.6 km section of tunnel being constructed through foliated crystalline metamorphic bedrock in a glaciated region of eastern Massachusetts. Lineaments drawn by three observers during two independent trials (N = 9137) were reduced to three sets (one per image type) of coincident lineaments (N = 794). Thirty-five coincident lineaments crossed the tunnel. Nineteen discrete flow zones, each producing > or = 19 L/min, were identified in the tunnel and used to quantify the reliability of lineament analysis as a method of predicting water-bearing features in glaciated metamorphic Thirteen (68%) of the flow zones correlate with coincident lineaments, six zones correlate with more than one image type, and one zone correlates with all three image types. Overall, without additional corroborating evidence, it is difficult to interpret in advance which lineaments will result in a successful correlation with water-producing zones in the subsurface and which ones will not. Most of the observed flow (80%) correlates with northwest-trending coincident lineaments; however, the majority of the flow (67%) associated with these lineaments is produced from structures that strike to the north or northeast. In addition, only 15 of the 35 coincident lineaments correlate with the flow zones, indicating that 20 lineaments are not associated with any appreciable flow. Six flow zones are undetected by the lineament analysis.

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