Search

Biomaterial wound dressings, such as hydrogels, interact with host cells to regulate tissue repair. This study investigates how crosslinking of gelatin-based hydrogels influences immune and stromal cell behavior and wound healing in female mice. We observe that softer, lightly crosslinked hydrogels promote greater cellular infiltration and result in smaller scars compared to stiffer, heavily crosslinked hydrogels. Using single-cell RNA sequencing, we further show that heavily crosslinked hydrogels increase inflammation and lead to the formation of a distinct macrophage subpopulation exhibiting signs of oxidative activity and cell fusion. Conversely, lightly crosslinked hydrogels are more readily taken up by macrophages and integrated within the tissue. The physical properties differentially affect macrophage and fibroblast interactions, with heavily crosslinked hydrogels promoting pro-fibrotic fibroblast activity that drives macrophage fusion through RANKL signaling. These findings suggest that tuning the physical properties of hydrogels can guide cellular responses and improve healing, offering insights for designing better biomaterials for wound treatment., (© 2024. The Author(s).)

Introduction: Even using well-established technology assessment processes, the basis of the decisions on drug price and reimbursement are sometimes perceived as poorly informed and sometimes may be seen as disconnected from value. The literature remains inconclusive about how Health Technology Assessment Bodies (HTAb) should report the determinants of their decisions. This study evaluates the relationship between oncology and hematology drug list prices and structured value parameters at the time of reimbursement decision in Spain., Methods: The study includes all new onco-hematological products (22), with a first indication authorized between January 2017 and December 2019 in Spain and pricing decisions published up until October 2022. For each product, 56 contextual and non-contextual indicators reflecting the structured multiple criteria decision analysis (MCDA) - Evidence-based Decision-Making (EVIDEM) framework were measured. The relationship between prices and the MCDA-EVIDEM framework was explored using univariate statistical analyses., Results: Higher prices were observed when the standard of care included for combinations, if there were references to long-lasting responses, for fixed-duration treatment compared to treatment until progression and treatment with lower frequencies of administration; lower prices were observed for oral administration compared to other routes of administration. Statistically significant associations were observed between prices and the median duration of treatment, the impact on patient autonomy, the ease of use of the drug, and the recommendations of experts., Discussion: The study suggests that indicators related to the type of standard of care, references to long-lasting responders, the convenience of the use of the drug, and the impact of treatment on patient autonomy, as well as contextual indicators such as the existence of previous clinical consensus, are factors in setting oncology drug prices in Spain. The implementation of MCDA-EVIDEM methodologies may be useful to capture the influence on pricing decisions of additional factors not included in legislation or consolidated assessment frameworks such as the European Network for Health Technology Assessment (EunetHTA) core model. It may be opportune to consider this in the upcoming revision of the Spanish regulation for health technology assessments and pricing and reimbursement procedures., Competing Interests: DE and MO are full-time employees of Sanofi. JT reports personal financial interest in the form of scientific consultancy roles for Array Biopharma, AstraZeneca, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F. Hoffmann-La Roche Ltd., Genentech Inc., HalioDX SAS, Hutchison MediPharma International, Ikena Oncology, Inspirna Inc., IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Ona Therapeutics, Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Scandion Oncology, Scorpion Therapeutics, Seattle Genetics, Servier, Sotio Biotech, Taiho, Tessa Therapeutics, TheraMyc, and Tolremo Therapeutics. Stocks: Oniria Therapeutics and educational collaboration with Imedex/HMP, Medscape Education, MJH Life Sciences, PeerView Institute for Medical Education, and Physicians Education Resource (PER). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Elvira, Torres, Vives, Puig, Obach, Gay, Varón, de Pando, Tabernero and Pontes.)

Background: Cervical cancer, the fourth most frequent cancer in women, is associated with the human papillomavirus (HPV). This study identifies risk factors and clinical findings for abnormal cervical cytology and histopathology in the Trinidad and Tobago populations. Some risk factors include early age of first coitus, a high number of sexual partners, high parity, smoking, and using certain medications, such as oral contraception. This study aims to identify the significance of Papanicolaou (pap) smears and the common risk factors that contribute to the development of premalignant and malignant cervical lesions. Method: A three-year retrospective, descriptive study of cervical cancer was conducted at the Eric Williams Medical Sciences Complex. The subject population included 215 female patients aged 18 years and older with the following documented abnormal cervical cytology: (ASCUS), ASC-H, LSIL, HSIL, Atypical Glandular cells, HPV, Adenocarcinoma, and Invasive Squamous Cell Carcinoma. Histopathology records were analysed for thirty-three of these patients. Patients' information was recorded on data collection sheets adapted from the North Central Regional Health Authority's cytology laboratory standardised reporting format request form. Results and Findings: The data were analysed via Statistical Package for Social Sciences (SPSS) software edition 23 using frequency tables and descriptive analysis. The mean sample age of the population was 36.7 years, the first age of coitus was 18.1 years, the number of sexual partners was 3.8, and the number of live births was 2. LSIL was the most popular abnormal finding, 32.6%, followed by HSIL, 28.8%, and ASCUS, 27.4%. Most histopathological reports resulted in CIN I and II. Conclusions : The significant risk factors observed for cytology abnormalities and premalignant lesions were early age of coitus, a high number of sexual partners, and no use of contraception. Patients mostly presented as asymptomatic despite obtaining abnormal cytology results. Hence, regular pap smear screening should continue to be highly encouraged.

Background: Neuroendocrine prostate cancer (NEPC) is a multi-resistant variant of prostate cancer (PCa) that has become a major challenge in clinics. Understanding the neuroendocrine differentiation (NED) process at the molecular level is therefore critical to define therapeutic strategies that can prevent multi-drug resistance., Methods: Using RNA expression profiling and immunohistochemistry, we have identified and characterised a gene expression signature associated with the emergence of NED in a large PCa cohort, including 169 hormone-naïve PCa (HNPC) and 48 castration-resistance PCa (CRPC) patients. In vitro and preclinical in vivo NED models were used to explore the cellular mechanism and to characterise the effects of castration on PCa progression., Results: We show for the first time that Neuropilin-1 (NRP1) is a key component of NED in PCa cells. NRP1 is upregulated in response to androgen deprivation therapies (ADT) and elicits cell survival through induction of the PKC pathway. Downmodulation of either NRP1 protein expression or PKC activation suppresses NED, prevents tumour evolution toward castration resistance and increases the efficacy of docetaxel-based chemotherapy in preclinical models in vivo., Conclusions: This study reveals the NRP1/PKC axis as a promising therapeutic target for the prevention of neuroendocrine castration-resistant variants of PCa and indicates NRP1 as an early transitional biomarker., (© 2022. The Author(s).)

Background: Teprotumumab is the first treatment for thyroid eye disease (TED), a debilitating autoinflammatory condition, approved by the Food and Drug Administration in the United States, which reduces proptosis and improves quality of life. In the absence of guidelines, clinical recommendations were developed for using teprotumumab in patients with TED in the United States., Methods: A 3-round modified-Delphi panel was conducted between October 2020 and February 2021 with experts in the management of patients with TED. Key areas regarding the use of teprotumumab were investigated, including eligible patient populations, concomitant treatments, and assessment of response and adverse events. This used 2 survey rounds via an online questionnaire, where statements were scored using 9-point Likert scales. Statements with conflict were included in the third round, involving a consensus meeting via videoconference., Results: Consensus was obtained for all statements (n = 75); of which, 56% were revised to enable agreement of the group. The consensus meeting provided agreement regarding which populations should receive teprotumumab therapy, including all adult patients with TED with a clinical activity score of ≥4. Treatment with teprotumumab can also be considered for TED patients displaying the following characteristics: a CAS of <3, lid retraction of ≥2, and mild or early optic neuropathy with close clinical observation. Further recommendations included suitability of treatment for those beyond 16 months following the initial diagnosis of TED, low CAS concomitant treatment with steroids in some cases, retreatment for those who have relapses, and finally a recommendation to continue therapy for all 8 infusions despite the lack of response by the fourth infusion., Conclusions: This work constitutes the first consensus on guidelines for the use of teprotumumab. The modified Delphi approach involved physicians with significant experience with the clinical use of teprotumumab, and recommendations were based on current evidence., Competing Interests: R. S Douglas: Consultant Horizon Therapeutics, Immunovant Corporation, and Veridian Corporation. A. L. Kossler: Consultant Horizon Therapeutics, Osmotica Pharmaceuticals, Immunovant Corporation, and Axogen Corporation. J. Abrams: Speaker for Horizon Therapeutics. C. A. Briceño: Consultant for Horizon Therapeutics. A. Harrison: Consultant for Horizon Therapeutics and Osmotica. M. Lee: Equity ownership, Horizon Therapeutics. J. Nguyen: Consultant for Horizon Therapeutics. S. S. Joseph: Consultant for Horizon Therapeutics. J. Tan: Consultant for Horizon Therapeutics. The remaining authors report no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the North American Neuro-Opthalmology Society.)

Time is a fundamental component of ecological processes. How animal behavior changes over time has been explored through well-known ecological theories like niche partitioning and predator-prey dynamics. Yet, changes in animal behavior within the shorter 24-hr light-dark cycle have largely gone unstudied. Understanding if an animal can adjust their temporal activity to mitigate or adapt to environmental change has become a recent topic of discussion and is important for effective wildlife management and conservation. While spatial habitat is a fundamental consideration in wildlife management and conservation, temporal habitat is often ignored. We formulated a temporal resource selection model to quantify the diel behavior of 8 mammal species across 10 US cities. We found high variability in diel activity patterns within and among species and species-specific correlations between diel activity and human population density, impervious land cover, available greenspace, vegetation cover, and mean daily temperature. We also found that some species may modulate temporal behaviors to manage both natural and anthropogenic risks. Our results highlight the complexity with which temporal activity patterns interact with local environmental characteristics, and suggest that urban mammals may use time along the 24-hr cycle to reduce risk, adapt, and therefore persist, and in some cases thrive, in human-dominated ecosystems., Competing Interests: TG, MF, BG, AA, JA, MA, AC, DD, DG, EL, MM, TR, CS, CS, HS, TS, JW, JB, KS, SM No competing interests declared

Oxidative phosphorylation (OXPHOS) defects caused by somatic mitochondrial DNA (mtDNA) mutations increase with age in human colorectal epithelium and are prevalent in colorectal tumours, but whether they actively contribute to tumorigenesis remains unknown. Here we demonstrate that mtDNA mutations causing OXPHOS defects are enriched during the human adenoma/carcinoma sequence, suggesting they may confer a metabolic advantage. To test this we deleted the tumour suppressor Apc in OXPHOS deficient intestinal stem cells in mice. The resulting tumours were larger than in control mice due to accelerated cell proliferation and reduced apoptosis. We show that both normal crypts and tumours undergo metabolic remodelling in response to OXPHOS deficiency by upregulating the de novo serine synthesis pathway (SSP). Moreover, normal human colonic crypts upregulate the SSP in response to OXPHOS deficiency prior to tumorigenesis. Our data show that age-associated OXPHOS deficiency causes metabolic remodelling that can functionally contribute to accelerated intestinal cancer development., Competing Interests: Competing interests: F.O is a director of Fibrofind limited. J.L and F.O are shareholders in Fibrofind limited. The remaining authors declare no competing financial interests.

Objectives: Team rounding in the ICU can tax clinicians' finite attentional resources. We hypothesized that a novel approach to rounding, where patients are seen in a decreasing order of acuity, would decrease attentional attrition., Design: Prospective interventional internal-control cohort study in which stop signal task testing was used as a proxy for attentional reserves. Stop signal task is a measure of cognitive control and response inhibition in addition to performance monitoring, all reflective of executive control abilities, and our surrogate for attentional reserves., Setting: The ICUs of Vanderbilt University Medical Center (site 1) and the University of Pennsylvania (site 2) from November 2014 to August 2017., Subjects: Thirty-three clinicians at site 1, and 24 clinicians at site 2., Interventions: Acuity-based rounding, in which clinicians round from highest to lowest acuity as determined by Sequential Organ Failure Assessment score or an equivalent acuity score., Measurements and Main Results: The stop signal task results of ICU staff at two sites were compared for conventional (in room order) versus novel (in decreasing order of acuity) rounding order. At site 1, the difference in stop signal reaction time change between two rounding types was -39.0 ms (95% CI, -50.6 to -27.4 ms; p < 0.001), and at site 2, the performance stop signal reaction time was -15.6 ms (95% CI, -29.1 to -2.1 ms; p = 0.023). These sub-second changes, while small, are significant in the neuroscience domain., Conclusions: Rounding in decreasing order of patient acuity mitigated attrition in attentional reserves when compared with the traditional rounding method.

Human and murine skin wounding commonly results in fibrotic scarring, but the murine wounding model wound-induced hair neogenesis (WIHN) can frequently result in a regenerative repair response. Here, we show in single-cell RNA sequencing comparisons of semi-regenerative and fibrotic WIHN wounds, increased expression of phagocytic/lysosomal genes in macrophages associated with predominance of fibrotic myofibroblasts in fibrotic wounds. Investigation revealed that macrophages in the late wound drive fibrosis by phagocytizing dermal Wnt inhibitor SFRP4 to establish persistent Wnt activity. In accordance, phagocytosis abrogation resulted in transient Wnt activity and a more regenerative healing. Phagocytosis of SFRP4 was integrin-mediated and dependent on the interaction of SFRP4 with the EDA splice variant of fibronectin. In the human skin condition hidradenitis suppurativa, phagocytosis of SFRP4 by macrophages correlated with fibrotic wound repair. These results reveal that macrophages can modulate a key signaling pathway via phagocytosis to alter the skin wound healing fate., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

The Gulf of Mexico region has important sources of acid rain precursors, located in all of the countries; U.S., Mexico and Cuba, and so it is very important to study the chemical composition of the wet atmospheric deposition in all coastal areas. For many years along the U.S. Gulf Coast, acidic precipitation has been measured. Measurements along the Mexican Gulf Coast were begun in 2003. The aim of this study was to evaluate pH, sulfate, nitrate and ammonium concentrations in wet atmospheric deposition, collected daily from 2003 to 2015 at La Mancha (LM), Veracruz and compare the values with the National Atmospheric Deposition Program (NADP) sampling sites located along the U.S. coast of the Gulf of Mexico. The annual Volume Weighted Mean (VWM) pH in wet deposition at La Mancha site ranged from 4.81 to 5.40, which is similar to the U.S. Gulf sites. Additionally, the annual VWM SO 4 2- concentration was from 15 to 31 μeq/L, which is higher than the U.S. sites. Annual VWM NO 3 - concentrations were from of 3.5 to 15 μeq/L, which is lower than all the U.S. sites. At the Mexican site, the SO 4 2- /NO 3 - ratio was 4.90 and higher than all of the U.S. sites, which were between 1.03 and 2.38. For LM, the median NH 4 + /NO 3 - ratio was 0.77, similar to the Florida sites (0.53-0.91), and below the values measured for Louisiana and Texas (1.07-1.5). The Hybrid Single Particle Lagrangian Integrated Trajectory Model (HYSPLIT) was applied in order to identify the emission sources for the pollutants seen at LM. Trajectories showed an important transport to LM from the East (open water) during the rainy season. The region located East of La Mancha shows offshore petroleum operations as sources of acid rain precursors and deposition of acidifying and nitrogen containing compounds. It is important to consider the sulfur dioxide emission sources in the Mexico Gulf region, and to extend the atmospheric deposition sampling to other sites along the Mexican Gulf coast and Cuba., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Hair follicle stem cells may themselves regulate the niche environment for hair follicle regrowth. A recent Science paper from Elaine Fuchs and colleagues (Gur-Cohen et al., 2019) suggests that this involves regulation of the lymphatic system and may have implications in understanding tissue regeneration., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Tumours depend on altered rates of protein synthesis for growth and survival, which suggests that mechanisms controlling mRNA translation may be exploitable for therapy. Here, we show that loss of APC, which occurs almost universally in colorectal tumours, strongly enhances the dependence on the translation initiation factor eIF2B5. Depletion of eIF2B5 induces an integrated stress response and enhances translation of MYC via an internal ribosomal entry site. This perturbs cellular amino acid and nucleotide pools, strains energy resources and causes MYC-dependent apoptosis. eIF2B5 limits MYC expression and prevents apoptosis in APC-deficient murine and patient-derived organoids and in APC-deficient murine intestinal epithelia in vivo. Conversely, the high MYC levels present in APC-deficient cells induce phosphorylation of eIF2α via the kinases GCN2 and PKR. Pharmacological inhibition of GCN2 phenocopies eIF2B5 depletion and has therapeutic efficacy in tumour organoids, which demonstrates that a negative MYC-eIF2α feedback loop constitutes a targetable vulnerability of colorectal tumours.

Recent research shows that potentially cancerous, somatic mutations can reside in normal cells. Pineda et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201907178) report on a unique management technique by hair follicle stem cells to evade tumorigenesis., (© 2019 Gay and Ito.)

Hypoxia is a hallmark of solid tumours and a key physiological feature distinguishing cancer from normal tissue. However, a major challenge remains in identifying tractable molecular targets that hypoxic cancer cells depend on for survival. Here, we used SILAC-based proteomics to identify the orphan G protein-coupled receptor GPRC5A as a novel hypoxia-induced protein that functions to protect cancer cells from apoptosis during oxygen deprivation. Using genetic approaches in vitro and in vivo , we reveal HIFs as direct activators of GPRC5A transcription. Furthermore, we find that GPRC5A is upregulated in the colonic epithelium of patients with mesenteric ischaemia, and in colorectal cancers high GPRC5A correlates with hypoxia gene signatures and poor clinical outcomes. Mechanistically, we show that GPRC5A enables hypoxic cell survival by activating the Hippo pathway effector YAP and its anti-apoptotic target gene BCL2L1 Importantly, we show that the apoptosis induced by GPRC5A depletion in hypoxia can be rescued by constitutively active YAP. Our study identifies a novel HIF-GPRC5A-YAP axis as a critical mediator of the hypoxia-induced adaptive response and a potential target for cancer therapy., (© 2018 The Authors. Published under the terms of the CC BY 4.0 license.)

Excess nitrogen and phosphorus ("nutrients") loadings continue to affect ecosystem function and human health across the U.S. Our ability to connect atmospheric inputs of nutrients to aquatic end points remains limited due to uncoupled air and water quality monitoring. Where connections exist, the information provides insights about source apportionment, trends, risk to sensitive ecosystems, and efficacy of pollution reduction efforts. We examine several issues driving the need for better integrated monitoring, including: coastal eutrophication, urban hotspots of deposition, a shift from oxidized to reduced nitrogen deposition, and the disappearance of pristine lakes. Successful coordination requires consistent data reporting; collocating deposition and water quality monitoring; improving phosphorus deposition measurements; and filling coverage gaps in urban corridors, agricultural areas, undeveloped watersheds, and coastal zones.

Introduction: Focused assessment with sonography in trauma (FAST) is historically an effective method of assessing the patient in the trauma bay in order to aid decision-making and optimise patient outcomes. However, in the UK civilian practice, the use of FAST may decline given a recent change in National Institute for Health and Care Excellence guidance as a result of improvement in CT availability and resuscitation techniques., Method: In the Role 3 Medical Treatment Facility, Camp Bastion, 187 patients with trauma who received FAST in the trauma bay in 2014 were reviewed to determine the accuracy of FAST in the deployed environment., Results: The data demonstrates the sensitivity and specificity of FAST to be 75% and 99.3%, respectively., Conclusions: This study demonstrates that FAST is accurate on operations. FAST is provided by the integrated radiologist as part of damage control radiology, which gives the team leader rapid diagnostic information to improve decision-making and ultimately patient outcomes. CT is heavily utilised in civilian practice; however, the military operates in a different environment often with multiple casualties and limited access to CT, as a result, portable ultrasound will continue to be a valuable tool on operations if used properly. The next challenge is to develop and maintain this high diagnostic accuracy in future deployments where the memories of our prior success may fade., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Radon is the second leading cause of lung cancer after smoking. Since the previous quantitative risk assessment of indoor radon conducted in France, input data have changed such as, estimates of indoor radon concentrations, lung cancer rates and the prevalence of tobacco consumption. The aim of this work was to update the risk assessment of lung cancer mortality attributable to indoor radon in France using recent risk models and data, improving the consideration of smoking, and providing results at a fine geographical scale. The data used were population data (2012), vital statistics on death from lung cancer (2008-2012), domestic radon exposure from a recent database that combines measurement results of indoor radon concentration and the geogenic radon potential map for France (2015), and smoking prevalence (2010). The risk model used was derived from a European epidemiological study, considering that lung cancer risk increased by 16% per 100 becquerels per cubic meter (Bq/m 3 ) indoor radon concentration. The estimated number of lung cancer deaths attributable to indoor radon exposure is about 3000 (1000; 5000), which corresponds to about 10% of all lung cancer deaths each year in France. About 33% of lung cancer deaths attributable to radon are due to exposure levels above 100 Bq/m 3 . Considering the combined effect of tobacco and radon, the study shows that 75% of estimated radon-attributable lung cancer deaths occur among current smokers, 20% among ex-smokers and 5% among never-smokers. It is concluded that the results of this study, which are based on precise estimates of indoor radon concentrations at finest geographical scale, can serve as a basis for defining French policy against radon risk.

Exposure to radon is a well-established cause of lung cancer in the general population. The aim of the present work is to identify and summarize the results of studies that have assessed the risk of lung cancer due to indoor radon, based on a systematic review of relevant published studies. Sixteen studies from 12 different countries met eligibility criteria. Large differences in radon concentrations were noted between and within individual countries, and variety of risk models used to estimate the attributable fraction. Calculating again the attributable fraction in each of these studies using the same model (coefficient of 16% per 100 becquerels per cubic meter (Bq/m3) derived from the European residential radon study), the new attributable fraction of these selected studies ranged from 3% to 17%. Radon remains a public health concern. Information about radon health risks is important and efforts are needed to decrease the associated health problems., (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Despite numerous observations linking protracted exposure to low-dose (LD) radiation and leukemia occurrence, the effects of LD irradiation on hematopoietic stem cells (HSCs) remain poorly documented. Here, we show that adult HSCs are hypersensitive to LD irradiation. This hyper-radiosensitivity is dependent on an immediate increase in the levels of reactive oxygen species (ROS) that also promotes autophagy and activation of the Keap1/Nrf2 antioxidant pathway. Nrf2 activation initially protects HSCs from the detrimental effects of ROS, but protection is transient, and increased ROS levels return, promoting a long-term decrease in HSC self-renewal. In vivo, LD total body irradiation (TBI) does not decrease HSC numbers unless the HSC microenvironment is altered by an inflammatory insult. Paradoxically, such an insult, in the form of granulocyte colony-stimulating factor (G-CSF) preconditioning, followed by LD-TBI facilitates efficient bone marrow transplantation without myeloablation. Thus, LD irradiation has long-term detrimental effects on HSCs that may result in hematological malignancies, but LD-TBI may open avenues to facilitate autologous bone marrow transplantation., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

This corrects the article DOI: 10.1038/nature22056.

Emergency cricothyrotomy is a common feature in all difficult airway algorithms. It is the final step following a 'can't intubate, can't oxygenate' scenario. It is rarely performed and has a significant failure rate. There is variation in the reported size of the cricothyroid membrane, especially across population groups. Procedural failure may result from attempting to pass a device with too large an external diameter through the cricothyroid membrane. We aimed to determine the maximum height of the cricothyroid membrane in a UK trauma population. Electronic callipers were used to measure the maximum height of the cricothyroid membrane on 482 reformatted trauma computed tomography scans, 377 (78.2%) of which were in male patients. The mean (SD) height of the cricothyroid membrane, as independently measured by two radiologists, was 7.89 (2.21) mm and 7.88 (2.22) mm in male patients, and 6.00 (1.76) mm and 5.92 (1.71) mm in female patients. The presence of concurrent tracheal intubation or cervical spine immobilisation was found not to have a significant effect on cricothyroid membrane height. The cricothyroid membrane height in the study population was much smaller than that previously reported. Practitioners encountering patients who may require an emergency surgical airway should be aware of these data. Rescue airway equipment with variety of external diameters should be immediately available., (© 2017 The Association of Anaesthetists of Great Britain and Ireland.)

The non-essential amino acids serine and glycine are used in multiple anabolic processes that support cancer cell growth and proliferation (reviewed in ref. 1). While some cancer cells upregulate de novo serine synthesis, many others rely on exogenous serine for optimal growth. Restriction of dietary serine and glycine can reduce tumour growth in xenograft and allograft models. Here we show that this observation translates into more clinically relevant autochthonous tumours in genetically engineered mouse models of intestinal cancer (driven by Apc inactivation) or lymphoma (driven by Myc activation). The increased survival following dietary restriction of serine and glycine in these models was further improved by antagonizing the anti-oxidant response. Disruption of mitochondrial oxidative phosphorylation (using biguanides) led to a complex response that could improve or impede the anti-tumour effect of serine and glycine starvation. Notably, Kras-driven mouse models of pancreatic and intestinal cancers were less responsive to depletion of serine and glycine, reflecting an ability of activated Kras to increase the expression of enzymes that are part of the serine synthesis pathway and thus promote de novo serine synthesis.

Purpose: We report a 75-year-old woman with a history of multiple myeloma immunoglobulin D (IgD) variant, who presented with an epibulbar plasmacytoma masquerading as a subconjunctival hemorrhage., Methods: Magnetic resonance imaging of the brain and orbits with and without contrast was obtained and surgical biopsy of the subconjunctival lesion was performed; histopathology confirmed the diagnosis of plasmacytoma., Results: Subconjunctival biopsy revealed a plasma cell neoplasm infiltrate in the episcleral layer. The subconjunctival biopsy stained positive for CD138 and lambda-immunohistochemistry in the majority of plasma cells. Histologic findings were consistent with involvement by known IgD plasma cell myeloma where previous bone marrow biopsy demonstrated myeloma cells which stained monoclonally for IgD-lambda light chains., Conclusions: Although plasma cell neoplasms seldom present with ocular manifestations, it is crucial to recognize that these tumors may be associated with multiple myeloma. In patients with known multiple myeloma who present with subconjunctival hemorrhage, close follow-up is highly recommended, as this may be the initial presentation of an ocular plasmacytoma. Although a plasmacytoma is a rare subconjunctival lesion, it should not be immediately excluded from the differential diagnosis of such lesions.

Rugby league involves frequent periods of high-intensity running including acceleration and deceleration efforts, often occurring at low speeds., Purpose: To quantify the energetic cost of running and acceleration efforts during rugby league competition to aid in prescription and monitoring of training., Methods: Global positioning system (GPS) data were collected from 37 professional rugby league players across 2 seasons. Peak values for relative distance, average acceleration/deceleration, and metabolic power (P met ) were calculated for 10 different moving-average durations (1-10 min) for each position. A mixed-effects model was used to assess the effect of position for each duration, and individual comparisons were made using a magnitude-based-inference network., Results: There were almost certainly large differences in relative distance and P met between the 10-min window and all moving averages <5 min in duration (ES = 1.21-1.88). Fullbacks, halves, and hookers covered greater relative distances than outside backs, edge forwards, and middle forwards for moving averages lasting 2-10 min. Acceleration/deceleration demands were greatest in hookers and halves compared with fullbacks, middle forwards, and outside backs. P met was greatest in hookers, halves, and fullbacks compared with middle forwards and outside backs., Conclusions: Competition running intensities varied by both position and moving-average duration. Hookers exhibited the greatest P met of all positions, due to high involvement in both attack and defense. Fullbacks also reached high P met , possibly due to a greater absolute volume of running. This study provides coaches with match data that can be used for the prescription and monitoring of specific training drills.

Unlabelled: Rugby league coaches often prescribe training to replicate the demands of competition. The intensities of running drills are often monitored in comparison with absolute match-play measures. Such measures may not be sensitive enough to detect fluctuations in intensity across a match or to differentiate between positions., Purpose: To determine the position- and duration-specific running intensities of rugby league competition, using a moving-average method, for the prescription and monitoring of training., Methods: Data from a 15-Hz global positioning system (GPS) were collected from 32 professional rugby league players across a season. The velocity-time curve was analyzed using a rolling-average method, where maximum values were calculated for 10 different durations, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10 min, for each player across each match., Results: There were large differences between the 1- and 2-min rolling averages and all other rolling-average durations. Smaller differences were observed for rolling averages of greater duration. Fullbacks maintained a greater velocity than outside backs and middle and edge forwards over the 1- and 2-min rolling averages (ES 0.8-1.2, P < .05). For rolling averages 3 min and greater, the running demands of the fullbacks were greater than those of the middle forwards and outside backs (ES 1.1-1.4, P < .05)., Conclusions: These findings suggest that the running demands of rugby league fluctuate vastly across a match. Fullbacks were the only position to exhibit a greater running intensity than any other position, and therefore training prescription should reflect this.

Objectives: The aim of this study was to compare the sensitivity and specificity of chest digital tomosynthesis (DTS) with chest radiography (CXR) for the detection of noncalcified pulmonary nodules and hilar lesions using computed tomography (CT) as the reference standard., Materials and Methods: A total of 78 patients with suspected noncalcified pulmonary lesions on CXR were included in the study. Two radiologists, blinded to the history and CT, analyzed the CXR and the DTS images (separately), whereas a third radiologist analyzed the CXR and DTS images together. Noncalcified intrapulmonary nodules and hilar lesions were recorded for analysis. The interobserver agreement for CXR and DTS was assessed, and the time taken to report the images was recorded., Results: A total of 202 lesions were recorded in 78 patients. There were 111 true lesions confirmed on CT in 53 patients; in 25 patients subsequent CT excluded a lesion. The overall sensitivity was 32% for CXR and 49% for DTS. This improved to 54% when the posteroanterior CXR and DTS were reviewed together (CXR-DTS). The overall specificities for CXR, DTS, and CXR-DTS were 49%, 96%, and 98%, respectively. There were 56 suspected hilar lesions with subgroup sensitivities of 76% for CXR, 65% for DTS, and 76% for CXR-DTS. The specificity for hilar lesions was 59%, 92%, and 97% for CXR, DTS, and CXR-DTS, respectively., Conclusions: DTS significantly improves the detectability of noncalcified nodules when compared with and when used in combination with CXR. The specificity and interobserver agreement of DTS in the diagnosis of suspected noncalcified pulmonary nodules and hilar lesions are significantly better than those of CXR and approaches those of CT.

Objectives: To assess the capability of digital tomosynthesis (DTS) of the chest compared to a postero-anterior (PA) and lateral chest radiograph (CXR) in the diagnosis of suspected but unconfirmed pulmonary nodules and hilar lesions detected on a CXR. Computed tomography (CT) was used as the reference standard., Materials and Method: 78 patients with suspected non-calcified pulmonary nodules or hilar lesions on their CXR were included in the study. Two radiologists, blinded to the history and CT, prospectively analysed the CXR (PA and lateral) and the DTS images using a picture archiving and communication workstation and were asked to designate one of two outcomes: true intrapulmonary lesion or false intrapulmonary lesion. A CT of the chest performed within 4 weeks of the CXR was used as the reference standard. Inter-observer agreement and time to report the modalities were calculated for CXR and DTS., Results: There were 34 true lesions confirmed on CT, 12 were hilar lesions and 22 were peripheral nodules. Of the 44 false lesions, 37 lesions were artefactual or due to composite shadow and 7 lesions were real but extrapulmonary simulating non-calcified intrapulmonary lesions. The PA and lateral CXR correctly classified 39/78 (50%) of the lesions, this improved to 75/78 (96%) with DTS. The sensitivity and specificity was 0.65 and 0.39 for CXR and 0.91 and 1 for DTS. Based on the DTS images, readers correctly classified all the false lesions but missed 3/34 true lesions. Two of the missed lesions were hilar in location and one was a peripheral nodule. All three missed lesions were incorrectly classified on DTS as composite shadow., Conclusions: DTS improves diagnostic confidence when compared to a repeat PA and lateral CXR in the diagnosis of both suspected hilar lesions and pulmonary nodules detected on CXR. DTS is able to exclude most peripheral pulmonary nodules but caution and further studies are needed to assess its ability to exclude hilar lesions., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: As a routine part of clinical care, temperature measurement is a key indicator of illness. With the criterion standard of temperature measurement from the pulmonary artery catheter thermistor (PAT), which insertion of PAT carries significant risk to the patient, a noninvasive method that is accurate and precise is needed., Objectives: The purpose of this study was to measure the precision and accuracy of 2 commonly used methods of collecting body temperature: PAT considered the criterion standard and the temporal artery thermometer (TAT) in those patients with a temperature greater than 100.4°F., Methods: This is a repeated-measures design with each patient with a PAT in the intensive care unit acting as their own control to investigate the difference in PAT readings and readings from TAT in the core mode. Accuracy and precision were analyzed., Results: There were 60 subjects, 41 males and 19 females, with mean age of 60.8 years, and 97% (n = 58) were post-cardiac surgery. There was a statistically significant difference between PAT and TAT (101.0°F [SD, 0.5°F] vs 100.5°F [SD, 0.8°F]; bias, -0.49°F; P < .001). Differences in temperature between the 2 methods were clinically significant (ie, >0.9°F different) in 15 of 60 cases (25%). No TAT measurements were 0.9 F greater than the corresponding PAT measurement (0%; 95% confidence interval, 0%-6%)., Discussion: These data demonstrate the accuracy of TAT when compared with PAT in those with temperatures of 100.4°F or greater. This study demonstrates that TAT set to core mode is accurate with a 0.5°F lower temperature than PAT. There was 25% in variability in precision of TAT.

This article presents an overview of current knowledge about natural sources of radiation exposure and potential associated health risks. Natural radioactivity constitutes the main source of exposure to ionizing radiation of the French and world population. Exposure is both external (telluric and cosmic rays) and internal (radon inhalation and ingestion of radionuclides from food and drinking water). It varies according to altitude, geology, and individual way of life (housing, food habits). Epidemiological studies demonstrated an excess risk of lung cancer associated to domestic radon exposure, ranking radon at the second place of known lung cancer risk factors after smoking. Data currently available do not allow concluding to risks associated to other natural sources of exposure to ionizing radiation.

The translation of CARS imaging towards real time, high resolution, chemically selective endoscopic tissue imaging applications is limited by a lack of sensitivity in CARS scanning probes sufficiently small for incorporation into endoscopes. We have developed here a custom double clad fiber (DCF)-based CARS probe which is designed to suppress the contaminant Four-Wave-Mixing (FWM) background generated within the fiber and integrated it into a fiber based scanning probe head of a few millimeters in diameter. The DCF includes a large mode area (LMA) core as a first means of reducing FWM generation by ~3 dB compared to commercially available, step-index single mode fibers. A micro-fabricated miniature optical filter (MOF) was grown on the distal end of the DCF to block the remaining FWM background from reaching the sample. The resulting probe was used to demonstrate high contrast images of polystyrene beads in the forward-CARS configuration with > 10 dB suppression of the FWM background. In epi-CARS geometry, images exhibited lower contrast due to the leakage of MOF-reflected FWM from the fiber core. Improvements concepts for the fiber probe are proposed for high contrast epi-CARS imaging to enable endoscopic implementation in clinical tissue assessment contexts, particularly in the early detection of endoluminal cancers and in tumor margin assessment.

Digital tomosynthesis is a radiographic technique that generates a number of coronal raw images of a patient from a single pass of the x-ray tube. Tomosynthesis provides some of the tomographic benefits of computed tomography (CT), but at a much lower dose of radiation and cost when compared to CT. This review illustrates the range of practical applications of digital tomosynthesis of the chest., (Copyright © 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

No disease-modifying therapies are currently available for Alzheimer's disease (AD), a neurodegenerative disorder that affects more than 36 million people worldwide. Although cardiovascular risk factors such as hypertension and diabetes are increasingly implicated as contributing to the development of AD, the mechanisms whereby these factors influence pathological processes in the AD brain have not been defined. Here we propose, for the first time, vascular activation as a relevant mechanism in AD pathogenesis. We explore this hypothesis in two transgenic AD animal models: AD2576APPSwe (AD2576) and LaFerla 3xTg (3xTgAD) mice using the vascular activation inhibitor sunitinib. Our data show that in both AD animal models, the cerebrovasculature is activated and overexpresses amyloid beta, thrombin, tumor necrosis factor alpha, interleukin-1 beta, interleukin-6, and matrix metalloproteinase 9. Oral administration of sunitinib significantly reduces vascular expression of these proteins. Furthermore, sunitinib improves cognitive function, as assessed by several behavioral paradigms, in both AD animal models. Finally, oxidant injury of brain endothelial cells in culture, resulting in expression of inflammatory proteins, is mitigated by sunitinib. The current data, as well as published studies showing cerebrovascular activation in human AD, support further exploration of vascular-based mechanisms in AD pathogenesis. New thinking about AD pathogenesis and novel, effective treatments are urgently needed. Identification of "vascular activation" as a heretofore unexplored target could stimulate translational investigations in this newly defined area, leading to innovative therapeutic approaches for the treatment of this devastating disease.

RifDH10, the dehydratase domain from the terminal module of the rifamycin polyketide synthase, catalyzes the stereospecific syn dehydration of the model substrate (2S,3S)-2-methyl-3-hydroxypentanoyl-RifACP10, resulting in the exclusive formation of (E)-2-methyl-2-pentenoyl-RifACP10. RifDH10 does not dehydrate any of the other three diastereomeric, RifACP10-bound, diketide thioester substrates. On the other hand, when EryACP6, from the sixth module of the erythromycin polyketide synthase, is substituted for RifACP10, RifDH10 stereospecifically dehydrates only (2R,3R)-2-methyl-3-hydroxypentanoyl-EryACP6 to give exclusively (E)-2-methyl-2-pentenoyl-EryACP6, with no detectable dehydration of any of the other three diastereomeric, EryACP6-bound, diketides. An identical alteration in substrate diastereospecificity was observed for the corresponding N-acetylcysteamine or pantetheine thioester analogues, regardless of acyl chain length or substitution pattern. Incubation of (2RS)-2-methyl-3-ketopentanoyl-RifACP10 with the didomain reductase-dehydratase RifKR10-RifDH10 yielded (E)-2-methyl-2-pentenoyl-RifACP10, the expected product of syn dehydration of (2S,3S)-2-methyl-3-hydroxypentanoyl-RifACP10, while incubation with the corresponding EryACP6-bound substrate, (2RS)-2-methyl-3-ketopentanoyl-EryACP6, gave only the reduction product (2S,3S)-2-methyl-3-hydroxypentanoyl-EryACP6 with no detectable dehydration. These results establish the intrinsic syn dehydration stereochemistry and substrate diastereoselectivity of RifDH10 and highlight the critical role of the natural RifACP10 domain in chaperoning the proper recognition and processing of the natural ACP-bound undecaketide substrate. The 1.82 Å resolution structure of RifDH10 reveals the atomic-resolution details of the active site and allows modeling of the syn dehydration of the (2S,3S)-2-methyl-3-hydroxyacyl-RifACP10 substrate. These results suggest that generation of the characteristic cis double bond of the rifamycins occurs after formation of the full-length RifACP10-bound acyclic trans-unsaturated undecaketide intermediate, most likely during the subsequent macrolactamization catalyzed by the amide synthase RifF.

Understanding molecular mechanisms for regeneration of hair follicles provides new opportunities for developing treatments for hair loss and other skin disorders. Here we show that fibroblast growth factor 9 (Fgf9), initially secreted by γδ T cells, modulates hair follicle regeneration after wounding the skin of adult mice. Reducing Fgf9 expression decreases this wound-induced hair neogenesis (WIHN). Conversely, overexpression of Fgf9 results in a two- to threefold increase in the number of neogenic hair follicles. We found that Fgf9 from γδ T cells triggers Wnt expression and subsequent Wnt activation in wound fibroblasts. Through a unique feedback mechanism, activated fibroblasts then express Fgf9, thus amplifying Wnt activity throughout the wound dermis during a crucial phase of skin regeneration. Notably, humans lack a robust population of resident dermal γδ T cells, potentially explaining their inability to regenerate hair after wounding. These findings highlight the essential relationship between the immune system and tissue regeneration. The importance of Fgf9 in hair follicle regeneration suggests that it could be used therapeutically in humans.

A 78-year-old woman presented 28 days after a low-impact fall, where she sustained a right pubic ramus fracture, with increasing left hip pain and fever. Her blood results showed a high white cell count and deranged urea and electrolytes. An MRI revealed multiple osteoporotic fractures and bilateral gluteal abscesses with left iliopsoas abscess, which had likely formed in a haematoma of a sacral fracture. She received a long course of intravenous antibiotics and CT-guided drainage of the abscesses. She developed symptoms of cauda equina, but no evidence of epidural extension of the abscess was found at operation. She required neurorehabilitation. This case highlights the complications of pelvic osteoporotic fractures, and high associated morbidity and mortality in the elderly population.

Objectives: Wrist injuries are a common presentation to emergency departments. A clinical pathway has recently been introduced in our institution for patients with clinical suspicion of a scaphoid injury, using computed tomography (CT) at 2 weeks postinjury to rule out scaphoid fracture. However, it is not known what happens to patients who have a normal CT after such an injury. The aim of this pilot study was to assess disability after CT-negative wrist injuries., Methods: A prospective questionnaire study was undertaken to assess disability in patients who had a normal CT after clinical suspicion of a scaphoid fracture, using the Patient Rated Wrist Evaluation questionnaire. Adult patients were recruited at their first emergency department clinic review, where a baseline questionnaire was completed. Follow-up questionnaires were sent 3, 6 and 12 months later. Pain and function were assessed on a 0-10 scale, giving a total score out of 100., Results: Ninety-nine patients were initially recruited, of whom 72 had negative CT; 40 patients completed follow-up. There was a statistically significant reduction in pain, functional deficit and combined disability between baseline scores and 12-month follow-up. Overall, three (8%) patients had severe disability (pain and function combined), and six (15%) had moderate disability at 12 months., Conclusion: The majority of these patients recover from their injury, but a small proportion with normal CT scans have considerable disability 12 months after injury. Appropriate advice should be given to these patients to enable them to access further investigation and treatment.

Significant advances in the measurement of atmospheric mercury species have been made in the past 10 years yet limited protocols on quality control (QC) and assurance on this data have been published in the literature. Recently, considerable work has been done to develop quality control and assurance programs within North America. Environment Canada and the National Atmospheric Deposition Network (NADP) independently developed programs, RDMQ™ and AMQC, respectively, to QC atmospheric mercury speciation data (including gaseous elemental mercury (GEM), reactive gaseous mercury (RGM) and mercury associated to particles (PHg)). These 2 programs were assessed by the criteria on which the data is QCed and comparability of the final data products. Results show that the criteria used to flag data compare well within the 4 tested sites and that the number of flags for each criterion is generally comparable. The QC programs were applied to 2 distinct data sets and the final QCed data was compared. From a mid-latitude site, the final data sets compare very well and showed there to be a 0.3, 8.6 and 15% difference in the mean GEM, RGM and PHg concentrations post QC of each program. It is recommended that either the RDMQ or the AMQC programs be employed for a typical mid-latitude site. When the QC programs were applied to highly variable data, the data do not compare as well for RGM and PHg. Results showed a 2.7, 27 and 33% difference in the mean GEM, RGM and PHg concentrations, respectively, post QC of each program. It is recommended that RDMQ be used for data that is highly variable with high RGM/PHg concentrations as it allows for more manual correction over the QCed data. This investigation of 2 QC programs produced comparable data and that either of these programs can be used as standard methods for the quality control of atmospheric mercury speciation data., (This journal is © The Royal Society of Chemistry 2012)

Three sets of model predicted values for speciated mercury concentrations and dry deposition fluxes over the Great Lakes region were assessed using field measurements and model intercomparisons. The model predicted values were produced by the Community Multiscale Air Quality Modeling System for the year 2002 (CMAQ2002) and for the year 2005 (CMAQ2005) and by the Global/Regional Atmospheric Heavy Metals Model for the year 2005 (GRAHM2005). Median values of the surface layer ambient concentration of gaseous elemental mercury (GEM) from all three models were generally within 30% of measurements. However, all three models overpredicted surface-layer concentrations of gaseous oxidized mercury (GOM) and particulate bound mercury (PBM) by a factor of 2-10 at the majority of the 15 monitoring locations. For dry deposition of GOM plus PBM, CMAQ2005 showed a clear gradient with the highest deposition in Pennsylvania and its surrounding areas while GRAHM2005 showed no such gradient in this region; however, GRAHM2005 had more hot spots than those of CMAQ2005. Predicted dry deposition of GOM plus PBM from these models should be treated as upper-end estimates over some land surfaces in this region based on the tendencies of all the models to overpredict GOM and PBM concentrations when compared to field measurements. Model predicted GEM dry deposition was found to be as important as GOM plus PBM dry deposition as a contributor to total dry deposition. Predicted total annual mercury dry deposition were mostly lower than 5 μg m(-2) to the surface of the Great lakes, between 5 and 15 μg m(-2) to the land surface north of the US/Canada border, and between 5 and 40 μg m(-2) to the land surface south of the US/Canada border. Predicted dry deposition from different models differed from each other by as much as a factor of 2 at regional scales and by a greater extent at local scales., (Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.)

Introduction: Ultrasound (US) provides rapid effective assessment of the globe. In Afghanistan, ocular blast injuries are common. We present a case series demonstrating the value of US in this context., Methods: 29 patients with suspected blast eye injury had both computed tomography (CT) of the head and ocular US as part of their standard care in a military hospital in Afghanistan. The US images were assessed by blinded consultants (emergency department and radiology) and compared with the CT reports., Results: 18 patients had an intraocular injury on either CT or US. CT identified 11 injuries. US detected 18, including all 11 detected by CT. Inter-rater agreement was high (28/29)., Discussion: This series suggests that US may be as good as CT at detecting ocular blast injuries. However, inability to follow up local national patients meant that the clinical relevance of these findings cannot be quantified. US is likely to have a role on deployed operations in triaging possible ocular injuries., Conclusions: US is an easy, cheap alternative to CT for the assessment of blast injury to the eye. It appears to have identified all injuries detected by CT in this series and can be accurately interpreted by emergency physicians.

Vascular perturbations and hypoxia are increasingly implicated in Alzheimer's disease (AD) pathogenesis. Cerebral hypoxia induces a large number of inflammatory proteins in brain endothelial cells via signaling pathways that have not been defined. The p38 mitogen-activated protein kinase (MAPK) signaling system has been implicated in endothelial injury and inflammation. The objective of this study is to examine p38 MAPK levels in the cerebromicrovasulature in AD and AD animal models and determine the role of p38 MAPK signaling in hypoxia-mediated effects on brain endothelial cells. Western blot analysis of isolated human brain microvessels show that the phosphorylated (active) form of p38 MAPK (pp38 MAPK) is increased in vessels derived from AD brains compared to control-derived vessels. Similarly, immunofluorescent analysis reveals an increase in cerebrovascular pp38 MAPK as well as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in transgenic AD mice. Exposure of brain endothelial cells to hypoxia (2-6 hours) shows a time-dependent increase in pp38 MAPK. Examination of these cultures at 6 hours hypoxia shows that iNOS and COX-2 are significantly elevated and that the selective p38 MAPK inhibitor SB203580 significantly reduces the hypoxia-mediated increase in their expression. Inhibition of p38 MAPK in cultured brain endothelial cells also significantly decreases the hypoxia-induced increase in the inflammatory proteins, matrix metalloproteinase-2 and angiopoietin-2. These data demonstrate that pp38 MAPK is a key regulator of hypoxia in the cerebrovasculature and suggest that control of this signaling pathway could have therapeutic value in AD and other disorders where hypoxia is involved.

A partnership of federal and state agencies, tribes, industry, and scientists from academic research and environmental organizations is establishing a national, policy-relevant mercury monitoring network, called MercNet, to address key questions concerning changes in anthropogenic mercury emissions and deposition, associated linkages to ecosystem effects, and recovery from mercury contamination. This network would quantify mercury in the atmosphere, land, water, and biota in terrestrial, freshwater, and coastal ecosystems to provide a national scientific capability for evaluating the benefits and effectiveness of emission controls. Program development began with two workshops, convened to establish network goals, to select key indicators for monitoring, to propose a geographic network of monitoring sites, and to design a monitoring plan. MercNet relies strongly on multi-institutional partnerships to secure the capabilities and comprehensive data that are needed to develop, calibrate, and refine predictive mercury models and to guide effective management. Ongoing collaborative efforts include the: (1) development of regional multi-media databases on mercury in the Laurentian Great Lakes, northeastern United States, and eastern Canada; (2) syntheses and reporting of these data for the scientific and policy communities; and (3) evaluation of potential monitoring sites. The MercNet approach could be applied to the development of other monitoring programs, such as emerging efforts to monitor and assess global mercury emission controls.

Background: Nonarteritic ischemic optic neuropathy (NAION) is the most common acute optic neuropathy in adults over the age of 50. Patients affected notice sudden and painless loss of vision in 1 eye, often upon awaking. Studies have found that the opposite eye may be affected in approximately 15% to 20% of cases within a 5-year period. NAION vision loss results from an ischemic event often affecting the short posterior ciliary arteries. This results in optic nerve pallor, nerve fiber layer defects, and corresponding visual field defects., Case Reports: Two cases of NAION are discussed here. The first patient, a 57-year-old woman, had a 10-year history of visual symptoms, and the second, a 66-year-old man, presented in less than a week after first noticing symptoms. Both had predisposing systemic risk factors and resultant visual field loss and decreased visual acuity., Conclusions: Predisposing factors for NAION include small cup-to-disc ratios of the optic nerve, obstructive sleep apnea, nocturnal hypotension, diabetes, and other vascular diseases. The vision loss is irreversible, and there is no known effective treatment to prevent subsequent disc atrophy or recurring episodes., (Published by Elsevier Inc.)

To minimize crop loss by assisting in timely disease management and reducing fungicide use, an integrated atmospheric model was developed and tested for predicting the risk of occurrence of soybean rust in Minnesota. The model includes a long-range atmospheric spore transport and deposition module coupled to a leaf wetness module. The latter is required for spore germination and infection. Predictions are made on a daily basis for up to 7 days in advance using forecast data from the United States National Weather Service. Complementing the transport and leaf wetness modules, bulk (wet plus dry) atmospheric deposition samples from Minnesota were examined for soybean rust spores using a specific DNA test and sequence analysis. Overall, the risk prediction worked satisfactorily within the bounds of the uncertainty associated with the use of modeled 7-day weather forecasts, with more than 65% agreement between the model forecast and the DNA test results. The daily predictions are available as an advisory to the user community through the University of Minnesota Extension. However, users must take the actual decision to implement the disease management strategy.

Background: Bilateral, recurrent, or chronic anterior uveitis requires a diagnostic evaluation to rule out any systemic cause. An understanding of the possible etiologies and their diagnostic criteria is needed to manage these patients. Treating any systemic cause can decrease the recurrent or chronic nature of the uveitis and favorably alter the course. Many possible systemic conditions are capable of causing anterior uveitis, including sarcoidosis., Case Reports: Two cases of chronic, recurrent, bilateral uveitis are presented. Both were evaluated for any systemic etiology. After extensive systemic workups, the first case had no identifiable systemic etiology, whereas the second case was associated with systemic sarcoidosis., Conclusion: Although a medical workup may be necessary, it will not always lead to a systemic diagnosis. The literature indicates that up to about 50% of uveitic cases have no identified causes.

The trucking industry employs approximately 9 million workers, with approximately 3 million being long-haul truck drivers. Truck drivers are exposed to a variety of stressful situations, such as working long hours, no sleep, inadequate rest and relaxation, being away from home and support systems, and driving in hazardous conditions. These risk factors place the long-haul truck driver at an increased risk for possible use or abuse of alcohol and drugs. Identification of those at risk and those who are abusing alcohol and drugs is vitally important for the health of these truckers.

Background: A retrospective chart review study at a Veterans Affairs hospital evaluated intraocular pressure change after dorzolamide hydrochloride 2% was administered to patients already using travoprost. A literature search found no other study that looked specifically at this combination of drugs., Methods: A chart review of 46 patients at the Veterans Affairs Illiana Health Care System was performed evaluating the intraocular pressures after dorzolamide hydrochloride was added to travoprost. Baseline intraocular pressures were obtained on patients who had been on travoprost at least 4 months. Endpoint intraocular pressures were then obtained from the visit closest to 6 months after the addition of dorzolamide hydrochloride., Results: An average intraocular pressure reduction of an additional 20.6% was observed after adding only dorzolamide hydrochloride to travoprost., Conclusions: This study confirmed our clinical observations that dorzolamide hydrochloride added to travoprost is an excellent and safe choice to further lower intraocular pressures.

Background: Choroidal melanomas represent the most common primary malignancy of the eye. As primary eye care providers, optometrists must be able to identify suspicious lesions to facilitate proper referrals and timely treatment. Metastasis occurs in approximately 75% of cases. Ongoing studies such as the Collaborative Ocular Melanoma Study are bringing new information on how to best manage choroidal melanoma. Current treatments include enucleation, plaque brachytherapy, and transpupillary thermotherapy., Case Report: Two patients presented to the Veterans Affairs (VA) Illiana Health Care System optometry clinic for routine visits and had malignant melanomas diagnosed. The first patient was in for a 6-month routine glaucoma follow-up, noting that the right eye seemed to be worse. The second patient was new, complaining of a painful, red eye. Both were referred to a retinal specialist and later treated by an ocular oncologist with enucleation and plaque brachytherapy, respectively. Their differing chief complaints and cases are discussed., Conclusion: Patients with malignant choroidal melanomas present with a wide variety of complaints, and optometrists need to be diligent in properly assessing the cause of seemingly common conditions, such as anterior uveitis, as well as performing routine dilated fundus examinations. Given the relationship between size and prognosis, early detection is important.