Environmental sampling methods' influence on detection of pathogens in cage-free aviary housing.

The environmental sampling of layer housing systems is essential to identifying potential pathogens that are of concern to human health. To identify the natural occurrence of pathogens (Listeria, Campylobacter, and Salmonella) at various locations in a cage-free aviary housing system, swabs were collected when hens were 22 to 39 wks of age. Duplicate environmental swabs were taken and inoculated with a low dose (101 cfu) Salmonella Enteritidis (SE) and examined for the recovery of SE from environmental samples. Detection of Listeria (P < 0.0001) and Campylobacter (P < 0.0001) varied between the environmental sample types taken: concrete dust, drag swabs, egg belt dust, manure belt scraper swabs, and wall dust. Detection of Listeria (P < 0.0001) was the highest (70.0%) at the beginning of the study (22 wk) and decreased over time. Detection of Campylobacter (P < 0.001) was also the highest at 22 wk, however the decrease over time was more gradual. Interestingly, detection of Campylobacter (P < 0.0001) was the greatest in concrete dust samples (96.25%), which can be attributed to the presence of rodent excreta in the samples. Drag swabs and manure belt scraper swabs were the best sampling types for high detection of Listeria and Campylobacter. It should be noted that Listeria recovered was not of human health concern. No naturally occurring Salmonella was identified in this study. The recovery of the SE inoculum increased over time, reaching the greatest recovery in drag (81.25%; P < 0.0001), egg belt dust (100.00%; P < 0.0001) and wall dust swabs (100.00%; P < 0.0001) by 39 wk. This high rate of SE recovery occurred just before US mandatory SE environmental monitoring at 40 to 45 wks of age. Based on this study, the use of drag and manure belt scraper swabs are effective in detecting Listeria and Campylobacter in cage-free aviary housing. Along with good pest management, the occurrence of pathogens could be monitored and reduced in laying hen flocks.

Prognosis after neoadjuvant chemoradiation or chemotherapy for locally advanced gastro-oesophageal junctional adenocarcinoma.

BACKGROUND: Trials typically group cancers of the gastro-oesophageal junction (GOJ) with oesophageal or gastric cancer when studying neoadjuvant chemoradiation and perioperative chemotherapy, so the results may not be fully applicable to GOJ cancer. Because optimal neoadjuvant treatment for GOJ cancer remains controversial, outcomes with neoadjuvant chemoradiation versus chemotherapy for locally advanced GOJ adenocarcinoma were compared retrospectively. METHODS: Data were collected from all patients who underwent neoadjuvant treatment followed by surgery for adenocarcinoma located at the GOJ at a single high-volume institution between 2002 and 2017. Postoperative major complications and mortality were compared between groups using Fisher's exact test. Overall survival (OS) and disease-free survival (DFS) were assessed by log rank test and multivariable Cox regression analyses. Cumulative incidence functions were used to estimate recurrence, and groups were compared using Gray's test. RESULTS: Of 775 patients, 650 had neoadjuvant chemoradiation and 125 had chemotherapy. These groups were comparable in terms of clinical tumour and lymph node categories, although the chemoradiation group had greater proportions of white men, complete pathological response to chemotherapy, and smaller proportions of diffuse cancer, poor differentiation, and neurovascular invasion. Postoperative major complications (20.0 versus 17.6 per cent) and 30-day mortality (1.7 versus 1.6 per cent) were not significantly different between the chemoradiation and chemotherapy groups. After adjustment, type of therapy (chemoradiation versus chemotherapy) was not significantly associated with OS (hazard ratio (HR) 1.26, 95 per cent c.i. 0.96 to 1.67) or DFS (HR 1.27, 0.98 to 1.64). Type of recurrence (local, regional, or distant) did not differ after neoadjuvant chemoradiation versus chemotherapy. CONCLUSION: In patients undergoing surgical resection for locally advanced adenocarcinoma of the GOJ, OS and DFS did not differ significantly between patients who had neoadjuvant chemoradiation compared with chemotherapy.

Treating advanced cancer of the gastro-oesophageal junction (GOJ) poses a challenge given its location in the distal oesophagus and proximal stomach, and whether it should be treated as oesophageal or gastric cancer. Given the indistinct location, it is unclear whether GOJ cancer should be treated with neoadjuvant chemoradiation, which is the treatment of choice for advanced oesophageal cancers, or perioperative chemotherapy, which is the treatment of choice for advanced gastric cancers. Few studies have addressed treatment options specifically for GOJ cancers. This study investigated whether there was a difference in survival between patients with GOJ cancer who were treated with chemoradiation versus chemotherapy.

Rational design, synthesis and testing of novel tricyclic topoisomerase inhibitors for the treatment of bacterial infections part 1.

The alarming reduction in drug effectiveness against bacterial infections has created an urgent need for the development of new antibacterial agents that circumvent bacterial resistance mechanisms. We report here a series of DNA gyrase and topoisomerase IV inhibitors that demonstrate potent activity against a range of Gram-positive and selected Gram-negative organisms, including clinically-relevant and drug-resistant strains. In part 1, we present a detailed structure activity relationship (SAR) analysis that led to the discovery of our previously disclosed compound, REDX05931, which has a minimum inhibitory concentration (MIC) of 0.06 µg mL-1 against fluoroquinolone-resistant Staphylococcus aureus. Although in vitro hERG and CYP inhibition precluded further development, it validates a rational design approach to address this urgent unmet medical need and provides a scaffold for further optimisation, which is presented in part 2.

Laying hen production and welfare in enriched colony cages at different stocking densities.

Many laying hen companies in the United States are pledging to move away from intensive conventional cages to extensive housing systems. Enriched colony cages (ECC) are a practical alternative to conventional cage systems. Scientific research is limited on the effects of ECC on hen production and welfare. Therefore, the objective of this study was to evaluate the effects of stocking density on welfare and performance with the overall outcome to provide guidance on stocking density for ECC. At 16 wk, W-36 pullets were placed into 2 commercial ECC housing systems. Within each ECC enclosure, hens were allocated into 1 of 6 stocking densities: A) 465 to 484 cm2/bird, B) 581 to 606 cm2/bird, C) 652 to 677 cm2/bird, D) 754 to 780 cm2/bird, E) 799 to 832 cm2/bird, and F) 923 to 955 cm2/bird. Body weight, egg production, mortality, and Welfare Quality data were collected each 28 d period from 17 to 68 wk. The 6 ECC stocking densities had several transient effects on production measures within age periods with no difference in hen-day production (P > 0.05). Body weight was affected by stocking density (P < 0.05) where hens raised at stocking density A (465 to 484 cm2/bird) weighed at least 25 g less than hens from other stocking densities. Stocking density differences for Welfare Quality assessments were only apparent for feather coverage. Hens raised at stocking density A (465 to 484 cm2) consistently had the poorest (P < 0.05) crop, keel, belly, back, and rump feather coverage. The keel, neck, and back body regions had poorer feather coverage when hens were raised at stocking densities B (581 to 606 cm2) and C (652 to 677 cm2) compared to hens from lower stocking densities (P < 0.05). Therefore, the minimum area per hen housed in commercial ECC systems should be 754 cm2 per bird for greater feather coverage.

National guidelines may reduce socioeconomic disparities in treatment selection for esophageal cancer.

The 2011 National Comprehensive Cancer Network guidelines first incorporated the results of the landmark CROSS trial, establishing induction therapy (chemotherapy ± radiation) and surgery as the treatment standard for locoregional esophageal cancer in the United States. The effect of guideline publication on socioeconomic status (SES) inequalities in cancer treatment selection remains unknown. Patients diagnosed with Stage II/III esophageal cancer between 2004 and 2013 who underwent curative treatment with definitive chemoradiation or multimodality treatment (induction and surgery) were identified from the Surveillance, Epidemiology and End Results (SEER)-Medicare registry. Clinicopathologic characteristics were compared between the two therapies. Multivariable regression analysis was used to adjust for known factors associated with treatment selection. An interaction term with respect to guideline publication and SES was included Of the 2,148 patients included, 1,478 (68.8%) received definitive chemoradiation and 670 (31.2%) induction and surgery. Guideline publication was associated with a 16.1% increase in patients receiving induction and surgery in the low SES group (21.4% preguideline publication vs. 37.5% after). In comparison, a 4.5% increase occurred during the same period in the high SES status group (31.8% vs. 36.3%). After adjusting for factors associated with treatment selection, guideline publication was associated with a 78% increase in likelihood of receiving induction and surgery among lower SES patients (odds ratio 1.78; 95% confidence interval (CI): 1.05,3.03). Following the new guideline publication, patients living in low SES areas were more likely to receive optimal treatment. Increased dissemination of guidelines may lead to increased adherence to evidence-based treatment standards.

Pathologic features of response to neoadjuvant anti-PD-1 in resected non-small-cell lung carcinoma: a proposal for quantitative immune-related pathologic response criteria (irPRC).

Background: Neoadjuvant anti-PD-1 may improve outcomes for patients with resectable NSCLC and provides a critical window for examining pathologic features associated with response. Resections showing major pathologic response to neoadjuvant therapy, defined as ≤10% residual viable tumor (RVT), may predict improved long-term patient outcome. However, %RVT calculations were developed in the context of chemotherapy (%cRVT). An immune-related %RVT (%irRVT) has yet to be developed. Patients and methods: The first trial of neoadjuvant anti-PD-1 (nivolumab, NCT02259621) was just reported. We analyzed hematoxylin and eosin-stained slides from the post-treatment resection specimens of the 20 patients with non-small-cell lung carcinoma who underwent definitive surgery. Pretreatment tumor biopsies and preresection radiographic 'tumor' measurements were also assessed. Results: We found that the regression bed (the area of immune-mediated tumor clearance) accounts for the previously noted discrepancy between CT imaging and pathologic assessment of residual tumor. The regression bed is characterized by (i) immune activation-dense tumor infiltrating lymphocytes with macrophages and tertiary lymphoid structures; (ii) massive tumor cell death-cholesterol clefts; and (iii) tissue repair-neovascularization and proliferative fibrosis (each feature enriched in major pathologic responders versus nonresponders, P < 0.05). This distinct constellation of histologic findings was not identified in any pretreatment specimens. Histopathologic features of the regression bed were used to develop 'Immune-Related Pathologic Response Criteria' (irPRC), and these criteria were shown to be reproducible amongst pathologists. Specifically, %irRVT had improved interobserver consistency compared with %cRVT [median per-case %RVT variability 5% (0%-29%) versus 10% (0%-58%), P = 0.007] and a twofold decrease in median standard deviation across pathologists within a sample (4.6 versus 2.2, P = 0.002). Conclusions: irPRC may be used to standardize pathologic assessment of immunotherapeutic efficacy. Long-term follow-up is needed to determine irPRC reliability as a surrogate for recurrence-free and overall survival.

Effects of different litter substrates and induced molt on production performance and welfare quality parameters of white Leghorn hens housed in multi-tiered aviary system.

More than 90% of the commercial egg production in the United States is pledged to be in cage-free systems by 2025. Management practices like induced molting and litter area management have come under scrutiny because of the housing system change. The aim of this study was to determine the welfare and production implications of different litter substrates and also evaluate induced molting of hens in a cage-free system. Bovan White hens were housed in a multi-tier aviary system with daily access to open litter area of either Astroturf (AT), wood shavings (SH), or straw (ST) and bare concrete floor (CO) serving as control. At 68 wk of age, molt was induced in half of the hens whereas the other half continued without molting to 116 wk. Production and welfare parameters were measured periodically throughout first and second cycles. Litter substrate did not influence hen-day production and case-weight measurements. However, CO had the lowest total number of eggs produced during the first cycle (P < 0.05). Hen-day percentage was approximately 14% greater in molted hens during the second cycle with egg case weight being heavier in non-molt hens toward the end of second cycle (P < 0.05). The only welfare parameter influenced by litter substrate during the first cycle was a greater crop feather loss in AT than ST at mid-lay (P < 0.05). Keel deformations increased with age irrespective of the litter substrate with 91.5% of palpated hens having keel deformations at the end of first cycle (P < 0.05). Molting did not influence the keel palpation and footpad scores whereas frequency of moderate comb wound was greater in molt hens during molt (P < 0.05). Severe feather loss was seen in non-molt hens during the second cycle (P < 0.05). Litter substrate does not affect production and physical parameters of welfare of hens in a multi-tier aviary system. Additionally, induced molting can be successfully carried out in the multi-tier cage-free system.

Hen genetic strain and extended cold storage influence on physical egg quality from cage-free aviary housing system.

In the United States, there is an increase in need for cage-free eggs in retail and food manufacturing sectors. Understanding the impact of cage-free systems and the corresponding management on egg quality is pertinent as the U.S. industry adapts existing housing and builds new cage-free housing structures. A study was conducted comparing 2 brown shell and 2 white shell hen strains housed in a cage-free aviary system. Each set of eggs were placed in cold storage and assessed at 0, 2, 4, 8, and 12 wk. Eggs were collected at 21, 31, 42, and 60 wk of hen age. A full profile of physical quality measurements was conducted on up to 18 intact eggs for each hen strain/egg storage/hen age combination. Egg weight increased approximately 10 g for brown shell and 14 g for white shell eggs as hens aged. Many of the properties monitored were significantly impacted by all 3 main effects (hen strain, egg storage, and hen age) resulting in 3-way interactions. A brown and a white shell strain had stronger shells (44 N; P < 0.0001) than the remaining brown and white shell strains (42 N and 39 N, respectively). The current study also determined volume of shell, total length, maximum width, and percent length at maximum width to more accurately indicate egg shape than shape index. One brown shell strain produced eggs with the most consistent shape characteristics over the hen ages monitored. White shell eggs from the cage-free aviary housing produced the highest whole-egg total solids between 31 to 60 wk of hen age, whereas brown shell eggs resulted in the most consistent level of whole-egg total solids (22-23.5%). The brown and white shell strains in the current study produce cage-free aviary eggs with distinctive physical quality attributes. The outcomes from this study can be utilized by the U.S. egg industry in planning management strategies and market placement of cage-free eggs.

Impact of egg handling and conditions during extended storage on egg quality.

The international trade of shell eggs has become more important in recent years in order to feed a growing worldwide population, meet food manufacturing demands, and address supply issues during disease outbreaks or product recalls. The primary barriers for the export and import of shell eggs are: whether to wash eggs and egg storage temperature. The current study was undertaken to compare egg quality factors as influenced by egg washing and storage temperature. Three lots of nest run white shell eggs were collected on consecutive d from a commercial in-line egg production facility. The treatment and storage conditions were selected to encompass the primary egg handling and storage conditions utilized throughout the world: washed; washed, oiled; and unwashed stored at 4°C; and unwashed stored at 22°C. Eggs were assessed weekly from 0 to 15 wk. Percent egg weight loss was greatest for the unwashed 22°C eggs (15.72%) and least for washed, oiled 4°C (0.33%, P < 0.0001). Less than 24 h at 22°C had a greater impact on yolk shape measurements decline than 15 wk at 4°C (P < 0.05). After 15 wk, average Haugh unit scores for all refrigerated treatments were still Grade A, and unwashed 22°C dropped from Grade AA to almost Grade B in one week. Room temperature storage of eggs rapidly declines egg quality. Egg treatment did not impact egg quality factors when stored at 4°C. Washing and oiling eggs before refrigerated storage did suppress the rate of egg weight loss.

Bilateral peroneal artery aneurysms.

True aneurysm of the tibial arteries is a rare clinical condition. We report the case of a 67-year-old man who presented with a gradual onset of right calf swelling and pain. Imaging revealed large aneurysms arising from the proximal peroneal arteries bilaterally, measuring 7.4cm and 4cm on the right and left respectively. A detailed medical history, clinical examination and laboratory investigations did not identify evidence of an underlying cause. A surgical reconstruction with an interposition vein graft was successfully performed. To our knowledge, this is the first reported case of primary aneurysm of the peroneal artery in the English literature. We undertook a systematic literature review to identify all reported cases of primary aneurysms of the tibial arteries. The clinical presentation, modes of investigation and interventional treatments are discussed.

Pharmacokinetics and toxicity of the novel oral demethylating agent zebularine in laboratory and tumor bearing dogs.

The purpose of this study was to determine the plasma pharmacokinetics (PK) and toxicity of zebularine, an oral cytidine analog with demethylating activity, in dogs. Plasma zebularine concentrations were determined by HPLC-MS/MS following an oral zebularine dose of 8 or 4 mg kg-1 . Plasma zebularine clearance was constant. Mean maximum concentration (Cmax ) was 23 ± 4.8 and 8.6 ± 1.4 µM following 8 and 4 mg kg-1 , respectively. Mean half-life was 5.7 ± 0.84 and 7.1 ± 2.1 following 8 and 4 mg kg-1 , respectively. A single 8 mg kg-1 dose was well tolerated. Daily 4 mg kg-1 treatment in three laboratory dogs resulted in grade 4 neutropenia (n = 3), grade 1 anorexia (n = 2) and grade 1 or 2 dermatologic changes (n = 2). All adverse events resolved with supportive care. A 4 mg kg-1 dose every 21 days was well tolerated. A follow-up dose escalation study is in progress with a lower starting dose.

Influence of commercial laying hen housing systems on the incidence and identification of Salmonella and Campylobacter.

The housing of laying hens is important for social, industrial, and regulatory aspects. Many studies have compared hen housing systems on the research farm, but few have fully examined commercial housing systems and management strategies. The current study compared hens housed in commercial cage-free aviary, conventional cage, and enriched colony cage systems. Environmental and eggshell pool samples were collected from selected cages/segments of the housing systems throughout the production cycle and monitored for Salmonella and Campylobacter prevalence. At 77 wk of age, 120 hens per housing system were examined for Salmonella and Campylobacter colonization in the: adrenal glands, spleen, ceca, follicles, and upper reproductive tract. All isolates detected from environmental swabs, eggshell pools, and tissues were identified for serotype. Two predominant Salmonella were detected in all samples:S.Braenderup andS.Kentucky.Campylobacter coli and C. jejuni were the only Campylobacter detected in the flocks. Across all housing systems, approximately 7% of hens were colonized with Salmonella, whereas >90% were colonized with Campylobacter Salmonella Braenderup was the isolate most frequently detected in environmental swabs (P<0.0001) and housing system impacted Salmonella spp. shedding (P<0.0001).Campylobacter jejuni was the isolate most frequently found in environmental swabs (P<0.01), while housing system impacted the prevalence of C. coli and jejuniin ceca (P<0.0001). The results of this study provide a greater understanding of the impact of hen housing systems on hen health and product safety. Additionally, producers and academia can utilize the findings to make informed decisions on hen housing and management strategies to enhance hen health and food safety.

Impact of commercial housing systems and nutrient and energy intake on laying hen performance and egg quality parameters.

The US egg industry is exploring alternative housing systems for laying hens. However, limited published research related to cage-free aviary systems and enriched colony cages exists related to production, egg quality, and hen nutrition. The laying hen's nutritional requirements and resulting productivity are well established with the conventional cage system, but diminutive research is available in regards to alternative housing systems. The restrictions exist with limited availability of alternative housing systems in research settings and the considerable expense for increased bird numbers in a replicate due to alternative housing system design. Therefore, the objective of the current study was to evaluate the impact of nutrient and energy intake on production and egg quality parameters from laying hens housed at a commercial facility. Lohmann LSL laying hens were housed in three systems: enriched colony cage, cage-free aviary, and conventional cage at a single commercial facility. Daily production records were collected along with dietary changes during 15 production periods (28-d each). Eggs were analyzed for shell strength, shell thickness, Haugh unit, vitelline membrane properties, and egg solids each period. An analysis of covariance (ANCOVA) coupled with a principal components analysis (PCA) approach was utilized to assess the impact of nutritional changes on production parameters and monitored egg quality factors. The traits of hen-day production and mortality had a response only in the PCA 2 direction. This finds that as house temperature and Met intake increases, there is an inflection point at which hen-day egg production is negatively effected. Dietary changes more directly influenced shell parameters, vitelline membrane parameters, and egg total solids as opposed to laying hen housing system. Therefore, further research needs to be conducted in controlled research settings on laying hen nutrient and energy intake in the alternative housing systems and resulting impact on egg quality measures.

Microbiological impact of three commercial laying hen housing systems.

Hen housing for commercial egg production continues to be a societal and regulatory concern. Controlled studies have examined various aspects of egg safety, but a comprehensive assessment of commercial hen housing systems in the US has not been conducted. The current study is part of a holistic, multidisciplinary comparison of the diverse aspects of commercial conventional cage, enriched colony cage, and cage-free aviary housing systems and focuses on environmental and egg microbiology. Environmental swabs and eggshell pools were collected from all housing systems during 4 production periods. Total aerobes and coliforms were enumerated, and the prevalence of Salmonella and Campylobacter spp. was determined. Environmental aerobic and coliform counts were highest for aviary drag swabs (7.5 and 4.0 log cfu/mL, respectively) and enriched colony cage scratch pad swabs (6.8 and 3.8 log cfu/mL, respectively). Aviary floor and system wire shell pools had the greatest levels of aerobic contamination for all eggshell pools (4.9 and 4.1 log cfu/mL, respectively). Hens from all housing systems were shedding Salmonella spp. (89-100% of manure belt scraper blade swabs). The dry belt litter removal processes for all housing systems appear to affect Campylobacter spp. detection (0-41% of manure belt scraper blade swabs) considering detection of Campylobacter spp. was much higher for other environmental samples. Aviary forage area drag swabs were 100% contaminated with Campylobacter spp., whereas enriched colony cage scratch pads had a 93% positive rate. There were no differences in pathogen detection in the shell pools from the 3 housing systems. Results indicate egg safety is enhanced when hens in alternative housing systems use nest boxes. Additionally, current outcomes indicate the use of scratch pads in hen housing systems needs to be more thoroughly investigated for effects on hen health and egg safety.

Effect of a commercial housing system on egg quality during extended storage.

Egg producers in the United States are utilizing a variety of commercial egg production systems to provide consumer choice and meet legislative requirements. Consumer egg grades in the United States were developed for conventional cage production, and it is unclear what effect alternative production systems might have on egg quality during retail and consumer home storage. The current study was undertaken to determine what changes in egg quality characteristics occur during extended cold storage for commercially produced conventional cage, enriched colony cage, and cage-free aviary eggs. During 12 wk of cold storage, egg weight, albumen height, Haugh unit, static compression shell strength, vitelline membrane strength and deformation, yolk index, shell dynamic stiffness, and whole egg total solids were monitored. Overall, aviary and enriched eggs were significantly (P < 0.05) heavier than conventional cage. Albumen height and Haugh unit (P < 0.05) were significantly greater for conventional cage than enriched eggs. Static compression shell strength was greatest (P < 0.05) for enriched eggs compared with aviary. No overall housing system effects for yolk measurements, shell dynamic stiffness, or whole egg total solids were observed. Albumen height, Haugh unit, and yolk quality measurements were all greatest at 0 and lowest at 12 wk of storage (P < 0.05). The rate of quality change among the housing systems for each measured attribute at 4, 6, and 12 wk was determined. Other than differences in the change of egg weight at 4 wk, no significant differences in the rate of quality decline were found among the housing systems. The results of the current study indicate that current US egg quality standards should effectively define quality for commercially produced conventional cage, enriched colony cage, and cage-free aviary eggs.

Measuring midkine: the utility of midkine as a biomarker in cancer and other diseases.

Midkine (MK) is a pleiotropic growth factor prominently expressed during embryogenesis but down-regulated to neglible levels in healthy adults. Many published studies have demonstrated striking MK overexpression compared with healthy controls in various pathologies, including ischaemia, inflammation, autoimmunity and, most notably, in many cancers. MK expression is detectable in biopsies of diseased, but not healthy, tissues. Significantly, because it is a soluble cytokine, elevated MK is readily apparent in the blood and other body fluids such as urine and CSF, making MK a relatively convenient, accessible, non-invasive and inexpensive biomarker for population screening and early disease detection. The first diagnostic tests that quantify MK are just now receiving regulatory clearance and entering the clinic. This review examines the current state of knowledge pertaining to MK as a biomarker and highlights promising indications and clinical settings where measuring MK could make a difference to patient treatment. I also raise outstanding questions about reported variants of MK as well as MK's bio-distribution in vivo. Answering these questions in future studies will enhance our understanding of the significance of measured MK levels in both patients and healthy subjects, and may reveal further opportunities for measuring MK to diagnose disease. MK has already proven to be a biomarker that can significantly improve detection, management and treatment of cancer, and there is significant promise for developing further MK-based diagnostics in the future.

Site-specific water quality guidelines: 1. Derivation approaches based on physicochemical, ecotoxicological and ecological data.

Generic water quality guidelines (WQGs) are developed by countries/regions as broad scale tools to assist with the protection of aquatic ecosystems from the impacts of toxicants. However, since generic WQGs cannot adequately account for the many environmental factors that may affect toxicity at a particular site, site-specific WQGs are often needed, especially for high environmental value ecosystems. The Australian and New Zealand Guidelines for Fresh and Marine Water Quality provide comprehensive guidance on methods for refining or deriving WQGs for site-specific purposes. This paper describes three such methods for deriving site-specific WQGs, namely: (1) using local reference water quality data, (2) using biological effects data from laboratory-based toxicity testing, and (3) using biological effects data from field surveys. Two case studies related to the assessment of impacts arising from mining operations in northern Australia are used to illustrate the application of these methods. Finally, the potential of several emerging methods designed to assess thresholds of ecological change from field data for deriving site-specific WQGs is discussed. Ideally, multiple lines of evidence approaches, integrating both laboratory and field data, are recommended for deriving site-specific WQGs.

Highly sensitive covalently functionalised integrated silicon nanowire biosensor devices for detection of cancer risk biomarker.

In this article we present ultra-sensitive, silicon nanowire (SiNW)-based biosensor devices for the detection of disease biomarkers. An electrochemically induced functionalisation method has been employed to graft antibodies targeted against the prostate cancer risk biomarker 8-hydroxydeoxyguanosine (8-OHdG) to SiNW surfaces. The antibody-functionalised SiNW sensor has been used to detect binding of the 8-OHdG biomarker to the SiNW surface within seconds of exposure. Detection of 8-OHdG concentrations as low as 1 ng/ml (3.5 nM) has been demonstrated. The active device has been bonded to a disposable printed circuit which can be inserted into an electronic readout system as part of an integrated Point of Care (POC) diagnostic. The speed, sensitivity and ease of detection of biomarkers using SiNW sensors render them ideal for eventual POC diagnostics.

Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2.

BACKGROUND: Somatic mutations in the Janus kinase 2 gene (JAK2) occur in many myeloproliferative neoplasms, but the molecular pathogenesis of myeloproliferative neoplasms with nonmutated JAK2 is obscure, and the diagnosis of these neoplasms remains a challenge. METHODS: We performed exome sequencing of samples obtained from 151 patients with myeloproliferative neoplasms. The mutation status of the gene encoding calreticulin (CALR) was assessed in an additional 1345 hematologic cancers, 1517 other cancers, and 550 controls. We established phylogenetic trees using hematopoietic colonies. We assessed calreticulin subcellular localization using immunofluorescence and flow cytometry. RESULTS: Exome sequencing identified 1498 mutations in 151 patients, with medians of 6.5, 6.5, and 13.0 mutations per patient in samples of polycythemia vera, essential thrombocythemia, and myelofibrosis, respectively. Somatic CALR mutations were found in 70 to 84% of samples of myeloproliferative neoplasms with nonmutated JAK2, in 8% of myelodysplasia samples, in occasional samples of other myeloid cancers, and in none of the other cancers. A total of 148 CALR mutations were identified with 19 distinct variants. Mutations were located in exon 9 and generated a +1 base-pair frameshift, which would result in a mutant protein with a novel C-terminal. Mutant calreticulin was observed in the endoplasmic reticulum without increased cell-surface or Golgi accumulation. Patients with myeloproliferative neoplasms carrying CALR mutations presented with higher platelet counts and lower hemoglobin levels than patients with mutated JAK2. Mutation of CALR was detected in hematopoietic stem and progenitor cells. Clonal analyses showed CALR mutations in the earliest phylogenetic node, a finding consistent with its role as an initiating mutation in some patients. CONCLUSIONS: Somatic mutations in the endoplasmic reticulum chaperone CALR were found in a majority of patients with myeloproliferative neoplasms with nonmutated JAK2. (Funded by the Kay Kendall Leukaemia Fund and others.).

Housing system and laying hen strain impacts on egg microbiology.

Alternative hen housing is becoming more commonplace in the egg market. However, a complete understanding of the implications for alternative housing systems on egg safety has not been achieved. The current study examines the impact of housing Hy-Line Brown, Hy-Line Silver Brown, and Barred Plymouth Rock hens in conventional cage, cage-free, and free range egg production systems on shell microbiology. Eggs were collected at 4 sampling periods. Egg shell emulsion pools were formed and enumerated for total aerobic organisms, Enterobacteriaceae, and yeast and mold counts. Hy-Line Brown and Hy-Line Silver Brown hens produced eggs with significantly (P < 0.05 and 0.001, respectively) different levels of aerobic organisms dependent on housing system. Eggs from conventional cages had significantly different (P < 0.05) levels of aerobic contamination in relation to hen strain with Hy-Line Silver Brown having the greatest (4.57 log cfu/mL). Hy-Line Brown and Barred Plymouth Rock hens produced eggs with significantly different (P < 0.01) levels of Enterobacteriaceae among housing systems with conventional caged eggs having the lowest level of contamination for the hen strains. There were no differences within each strain among housing systems for yeast and mold contamination. The study shows that hen strain has an effect on egg microbial levels for various housing systems, and egg safety should be considered when making hen strain selections for each housing system.