Interaction between pentacene molecules and monolayer transition metal dichalcogenides.

Using first-principles calculations based on density-functional theory, we investigated the adsorption of pentacene molecules on monolayer two-dimensional transition metal dichalcogenides (TMD). We considered the four most popular TMDs, namely, MoS2, MoSe2, WS2 and WSe2, and we examined the structural and electronic properties of pentacene/TMD systems. We discuss how monolayer pentacene interacts with the TMDs, and how this interaction affects the charge transfer and work function of the heterostructure. We also analyse the type of band alignment formed in the heterostructure and how it is affected by molecule-molecule and molecule-substrate interactions. Such analysis is valuable since pentacene/TMD heterostructures are considered to be promising for application in flexible, thin and lightweight photovoltaics and photodetectors.

Increased Handpiece Speeds without Air Coolant: Aerosols and Thermal Impact.

This study assessed the impact of increased speed of high-speed contra-angle handpieces (HSCAHs) on the aerosolization of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surrogate virus and any concomitant thermal impact on dental pulp. A bacteriophage phantom-head model was used for bioaerosol detection. Crown preparations were performed with an NSK Z95L Contra-Angle 1:5 (HSCAH-A) and a Bien Air Contra-Angle 1:5 Nova Micro Series (HSCAH-B) at speeds of 60,000, 100,000, and 200,000 revolutions per minute (rpm), with no air coolant. Bioaerosol dispersal was measured with Φ6-bacteriophage settle plates, air sampling, and particle counters. Heating of the internal walls of the pulp chambers during crown preparation was assessed with an infrared camera with HSCAH-A and HSCAH-B at 200,000 rpm (water flows ≈15 mL min-1 and ≈30 mL min-1) and an air-turbine control (≈23.5 mL min-1) and correlated with remaining tissue thickness measurements. Minimal bacteriophage was detected on settle or air samples with no notable differences observed between handpieces or speeds (P > 0.05). At all speeds, maximum settled aerosol and average air detection was 1.00 plaque-forming units (pfu) and 0.08 pfu/m3, respectively. Irrespective of water flow rate or handpiece, both maximum temperature (41.5°C) and temperature difference (5.5°C) thresholds for pulpal health were exceeded more frequently with reduced tissue thickness. Moderate and strong negative correlations were observed based on Pearson's correlation coefficient, between remaining dentine thickness and either differential (r = -0.588) or maximum temperature (r = -0.629) measurements, respectively. Overall, HSCAH-B generated more thermal energy and exceeded more temperature thresholds compared to HSCAH-A. HSCAHs without air coolant operating at speeds of 200,000 rpm did not increase bioaerosolization in the dental surgery. Thermal risk is variable, dependent on handpiece design and remaining dentine thickness.

Dental Mitigation Strategies to Reduce Aerosolization of SARS-CoV-2.

Limiting infection transmission is central to the safety of all in dentistry, particularly during the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Aerosol-generating procedures (AGPs) are crucial to the practice of dentistry; it is imperative to understand the inherent risks of viral dispersion associated with AGPs and the efficacy of available mitigation strategies. In a dental surgery setting, crown preparation and root canal access procedures were performed with an air turbine or high-speed contra-angle handpiece (HSCAH), with mitigation via rubber dam or high-volume aspiration and a no-mitigation control. A phantom head was used with a 1.5-mL min-1 flow of artificial saliva infected with Φ6-bacteriophage (a surrogate virus for SARS-CoV-2) at ~108 plaque-forming units mL-1, reflecting the upper limits of reported salivary SARS-CoV-2 levels. Bioaerosol dispersal was measured using agar settle plates lawned with the Φ6-bacteriophage host, Pseudomonas syringae. Viral air concentrations were assessed using MicroBio MB2 air sampling and particle quantities using Kanomax 3889 GEOα counters. Compared to an air turbine, the HSCAH reduced settled bioaerosols by 99.72%, 100.00%, and 100.00% for no mitigation, aspiration, and rubber dam, respectively. Bacteriophage concentrations in the air were reduced by 99.98%, 100.00%, and 100.00% with the same mitigations. Use of the HSCAH with high-volume aspiration resulted in no detectable bacteriophage, both on nonsplatter settle plates and in air samples taken 6 to 10 min postprocedure. To our knowledge, this study is the first to report the aerosolization in a dental clinic of active virus as a marker for risk determination. While this model represents a worst-case scenario for possible SARS-CoV-2 dispersal, these data showed that the use of HSCAHs can vastly reduce the risk of viral aerosolization and therefore remove the need for clinic fallow time. Furthermore, our findings indicate that the use of particle analysis alone cannot provide sufficient insight to understand bioaerosol infection risk.

The impact of COVID-19 on population oral health.

Over the last year, coronavirus disease 2019 (COVID-19) has accumulated over 37 million cases and over one million deaths worldwide (WHO, 2020). With no population immunity or vaccine at hand, all but fifteen countries issued 'stay at home' orders in a bid to contain the spread of the virus and limit the healthcare burden. 'Lockdown' included closure of dental practices. Both the virus itself and the various Government responses have had a profound impact on the work, home and social lives of the entire population and are likely to impact the oral health of many people. These oral health effects can be attributed to those caused directly by the virus and those caused indirectly through the subsequent societal response. Direct effects of COVID-19 on oral health include ageusia (an official symptom of COVID-19) and case reports of vesiculobullous lesions and necrotising periodontal disease (Patel and Woolley 2020). The ageusia associated with COVID-19 is transient and reports of other oral manifestations are based on low-grade and disputed evidence. The direct effects of COVID-19 are likely to be of modest consequence for population oral health.

Opening the door: midwives' perceptions of two models of psychosocial assessment in pregnancy- a mixed methods study.

BACKGROUND: One in five women experience psychological distress in the perinatal period. To support women appropriately, Australian guidelines recommend routine depression screening and psychosocial risk assessment by midwives in pregnancy. However, there is some evidence that current screening processes results in higher rates of false positives. The Perinatal Integrated Psychosocial Assessment (PIPA) Project compared two models of psychosocial assessment and referral - Usual Care and the PIPA model - with a view to improving referral decisions. This paper describes midwives' perspectives on psychosocial assessment, depression screening and referral at the antenatal booking appointment and compares midwives' experiences with, and perspectives on, the two models of care under investigation. METHODS: A two-phase, convergent mixed methods design was used. Midwives providing antenatal care completed a self-report survey in phase one prior to implementation of the new model of psychosocial assessment (n = 26) and again in phase two, following implementation (n = 27). Sixteen midwives also participated in two focus groups in phase two. Quantitative and qualitative data were compared and integrated in the presentation of results and interpretation of findings. RESULTS: Midwives supported psychosocial assessment believing it was a catalyst for 'Opening the door" to conversations with women. Midwives were comfortable asking the questions and tailored their approach to build rapport and trust. Overall. midwives expressed favourable views towards the PIPA model. A greater proportion of midwives relied mostly or entirely on the suggested wording for the psychosocial questions in the PIPA model compared to Usual Care (44.4% vs 12.0%, χ2=5.17, p=.023, φ =-.36). All midwives reported finding the referral or action message displayed at the end of the PIPA psychosocial assessment to be 'somewhat' or 'very' helpful, compared to 42.3% in Usual Care (χ2 = 18.36, p < .001, φ = -.64). Midwives were also more likely to act on or implement the message often or all of the time) in the PIPA model (PIPA = 69.2% vs Usual Care = 32.0%, (χ2 = 5.66, p < .017, φ = -.37). CONCLUSION: The study identified benefits of the new model and can inform improvements in psychosocial screening, referral and related care processes within maternity settings. The study demonstrates that psychosocial assessment can, over time, become normalised and embedded in practice.

Evaluation of a pharmacist-led antimicrobial stewardship service in a pediatric emergency department.

Background To improve antimicrobial use, incorporation of a pharmacist in antimicrobial stewardship initiatives in the emergency department has been recommended. Recognizing the potential value, a pharmacist-led antimicrobial stewardship (AMS) service which included review and follow up of microbiology results for patients discharged from the pediatric emergency department (PED) with suspected infections was implemented at our local institution. Objective The objective of this study was to evaluate the impact of pharmacists delivering this service compared to usual care. Setting Pediatric emergency department at the IWK Health Centre in Halifax, Canada. Method This study was completed as a retrospective chart review of pediatric patients discharged from the PED 6 months before and after implementation of the pharmacist-led AMS service. Data was extracted from electronic medical records. Data were reported descriptively and compared using a two-sided chi-square test and ordinal logistic regression. Main outcome measures The primary outcome measure was rate of return visits to the PED within 96 h of initial presentation. Results This study included 1070 patient encounters pre-implementation and 1040 patient encounters post-implementation. The rate of return visits to the PED within 96 h was 12.0% (129/1070) pre-implementation vs. 10.0% (100/1049) post-implementation (p = 0.07). The rate of return visits or hospitalization at 30 days was 22.1% (237/1070) pre-implementation compared to 19.9% (207/1040) in the post-implementation phase (p = 0.21). Inappropriate antimicrobial therapy was identified more often in the pre-implementation phase (7.0%, 68/975) vs. the post-implementation phase (5.0%, 46/952), p = 0.047. Time to notification within the first day after discharge occurred more frequently in the post-implementation phase (53.3%, 80/150) as compared to the pre-implementation phase (40.3%, 52/129, p = 0.0298). Conclusion Although this pharmacist-led AMS service did not significantly affect the rate of return visits or hospitalization, it may have led to more judicious use of antimicrobial agents and faster time to notification.

The subfornical organ: A novel site for prolactin action.

Prolactin (PRL) is a peptide hormone that performs over 300 biological functions, including those that require binding to prolactin receptor (PRL-R) in neurones within the central nervous system (CNS). To enter the CNS, circulating PRL must overcome the blood-brain barrier. Accordingly, areas of the brain that do not possess a blood-brain barrier, such as the subfornical organ (SFO), are optimally positioned to interact with systemic PRL. The SFO has been classically implicated in energy and fluid homeostasis but has the potential to influence oestrous cyclicity and gonadotrophin release, which are also functions of PRL. We aimed to confirm and characterise the expression of PRL-R in the SFO, as well as identify the effects of PRL application on membrane excitability of dissociated SFO neurones. Using a quantitative real-time polymerase chain reaction, we found that PRL-R mRNA in the SFO of male and female Sprague Dawley rats did not significantly differ between juvenile and sexually mature rats (P = .34), male and female rats (P = .97) or across the oestrous cycle (P = .54). Patch-clamp recordings were obtained in juvenile male rats to further investigate the actions of PRL at the SFO. Dissociated SFO neurones perfused with 1 µmol L-1 PRL resulted in 2 responsive subpopulations of neurones; 40% depolarised (n = 15/43, 11.3 ± 1.7 mV) and 14% hyperpolarised (n = 6/43, -6.7 ± 1.4 mV) to PRL application. Within the range of 10 pmol L-1 to 1 µmol L-1 , the concentrations of PRL were not significantly different in either the magnitude (P = .53) or proportion (P = .19) of response. Furthermore, PRL application significantly reduced the transient K+ current in 67% of SFO neurones in voltage-clamp configuration (n = 6/9, P = .02). The stability in response to PRL and expression of PRL-R in the SFO suggests that PRL function is conserved across physiological states and circulating PRL concentrations, prompting further investigations aiming to clarify the nature of PRL function in the SFO.

Fruit Flies as Potential Vectors of Foodborne Illness.

Fruit flies are a familiar sight in many food service facilities. Although they have been long considered as "nuisance pests," some of their typical daily activities suggest they may pose a potential public health threat. The aim of this study was to provide evidence of the ability of small flies to transfer bacteria from a contaminated source, food, or waste to surfaces or ready-to-eat food. Laboratory experiments were conducted by using purpose-built fly enclosures to assess the bacterial transfer capability of fruit flies. Drosophila repleta were capable of transferring Escherichia coli O157:H7, Salmonella Saint Paul, and Listeria innocua from an inoculated food source to the surface of laboratory enclosures. In addition, using an inoculated doughnut and noncontaminated lettuce and doughnut surfaces, fly-mediated cross-contamination of ready-to-eat food was demonstrated. Fruit flies were shown to be capable of accumulating approximately 2.9 × 103 log CFU of E. coli per fly within 2 h of exposure to a contaminated food source. These levels of bacteria did not decrease over an observation period of 48 h. Scanning electron micrographs were taken of bacteria associated with fly food and contact body parts and hairs during a selection of these experiments. These data, coupled with the feeding and breeding behavior of fruit flies in unsanitary areas of the kitchen and their propensity to land and rest on food preparation surfaces and equipment, indicate a possible role for fruit flies in the spread of foodborne pathogens.

Trichloroacetic Acid Ingestion: Self-Harm Attempt.

OBJECTIVE: Trichloroacetic acid (TCAA), or trichloroethanoic acid, is a chemical analogue of acetic acid where three methyl group hydrogen atoms are replaced by chlorine. TCAAs are also abbreviated and referred to as TCAs, causing confusion with the psychiatric antidepressant drug class, especially among patients. TCAAs exist in dermatological treatments such as chemical peels or wart chemoablation medication. TCAA ingestion or overdose can cause gastric irritation symptoms including vomiting, diarrhea, or lassitude. This symptomatology is less severe than TCA overdose, where symptoms may include elevated body temperature, blurred vision, dilated pupils, sleepiness, confusion, seizures, rapid heart rate, and cardiac arrest. Owing to the vast difference in symptoms, the need for clinical intervention differs greatly. While overdose of either in a self-harm attempt can warrant psychiatric hospital admission, the risk of death in TCAA ingestion is far less. CASE REPORT: A patient ingested TCAA in the form of a commercially available dermatological chemical peel as a self-harm attempt, thinking that it was a more injurious TCA. CONCLUSION: Awareness among physicians, particularly psychiatrists, regarding this relatively obscure chemical compound (TCAA) and its use by suicidal patients mistakenly believing it to be a substance that can be significantly more lethal (TCA), is imperative.

Objective structured clinical examination for pharmacy students in Qatar: cultural and contextual barriers to assessment.

This study aimed to evaluate the feasibility and psychometric defensibility of implementing a comprehensive objective structured clinical examination (OSCE) on the complete pharmacy programme for pharmacy students in a Middle Eastern context, and to identify facilitators and barriers to implementation within new settings. Eight cases were developed, validated, and had standards set according to a blueprint, and were assessed with graduating pharmacy students. Assessor reliability was evaluated using inter-class coefficients (ICCs). Concurrent validity was evaluated by comparing OSCE results to professional skills course grades. Field notes were maintained to generate recommendations for implementation in other contexts. The examination pass mark was 424 points out of 700 (60.6%). All 23 participants passed. Mean performance was 74.6%. Low to moderate inter-rater reliability was obtained for analytical and global components (average ICC 0.77 and 0.48, respectively). In conclusion, OSCE was feasible in Qatar but context-related validity and reliability concerns must be addressed prior to future iterations in Qatar and elsewhere.

Objective structured clinical examination for pharmacy students in Qatar: cultural and contextual barriers to assessment

This study aimed to evaluate the feasibility and psychometric defensibility of implementing a comprehensive objective structured clinical examination [OSCE] on the complete pharmacy programme for pharmacy students in a Middle Eastern context, and to identify facilitators and barriers to implementation within new settings. Eight cases were developed, validated, and had standards set according to a blueprint, and were assessed with graduating pharmacy students. Assessor reliability was evaluated using inter-class coefficients [ICCs]. Concurrent validity was evaluated by comparing OSCE results to professional skills course grades. Field notes were maintained to generate recommendations for implementation in other contexts. The examination pass mark was 424 points out of 700 [60.6%]. All 23 participants passed. Mean performance was 74.6%. Low to moderate inter-rater reliability was obtained for analytical and global components [average ICC 0.77 and 0.48, respectively]. In conclusion, OSCE was feasible in Qatar but context-related validity and reliability concerns must be addressed prior to future iterations in Qatar and elsewhere

La présente étude avait pour objectif d'évaluer la faisabilité et la solidité psychométrique de la mise en place d'un examen clinique objectif structuré [ECOS] du programme pharmaceutique complet pour les étudiants en pharmacie au Moyen-Orient, ainsi que d'identifier les leviers et les obstacles à sa mise en place dans les nouveaux établissements. Huit cas ont été élaborés, validés, se sont vus attribuer des normes en fonction d'un modèle, et ont ensuite été soumis à des étudiants en pharmacie pour évaluation. La fiabilité des examinateurs a été mesurée au moyen de coefficients intra-classe [CIC]. La validité concourante a été évaluée en comparant les résultats de l'ECOS aux notes finales de cours sur les compétences professionnelles. Des notes d'observation ont été conservées en vue de la production de recommandations pour la mise en place du test dans d'autres contextes. La note de passage de l'examen était de 424 points sur 700 [soit 60,6%]. Les 23 participants ont tous réussi l'examen. La performance moyenne était de 74,6%. Des taux de fiabilité intra-examinateur faible à moyen ont été obtenus pour les composantes analytiques et globales [CIC moyen de 0,77 et 0,48 respectivement]. Pour conclure, l'ECOS était réalisable au Qatar, mais les questions de validité et de fiabilité dépendant du contexte doivent être prises en compte avant toute reproduction du test au Qatar et dans d'autres pays

Thromboelastography (TEG®) compared with total platelet count in thrombocytopenia haematological malignancy patients with bleeding: a pilot observational study.

BACKGROUND: There has been no reported use of Thromboelastography(®) (TEG(®) ) in assessing thrombocytopenic haematological malignancy (HM) patients experiencing bleeding. OBJECTIVES: To assess whether there are differences in TEG(®) variables in thrombocytopenic HM patients experiencing clinically significant bleeding compared with those not experiencing bleeding. METHODS: Thirty adult patients with HM and a total platelet count (TPC) of ≤ 30 × 10(9) L(-1) were observed for greater than or equal to grade two World Health Organisation (WHO) bleeding episodes for 72 h. They had TPC, TEG(®) parameters [maximal amplitude (MA), reaction time (R-time), alpha (α-angle) and functional fibrinogen (FF) levels], activated partial thromboplastin time (APTT) and prothrombin time (PT) measured at inclusion, 24 and 48 h. RESULTS: Five patients had nine significant bleeding episodes. Patients bleeding (n) were all more hypocoaguable when measured by TEG(®) than patients not bleeding at inclusion n = 4 (MA: 16.9 vs 31.8 mm, P < 0.01; R-time: 10.1 vs 7.5 min, P = 0.02; α-angle: 18.8 vs 28.4, P < 0.01; FF: 182.4 vs 204 mg dL(-1), P < 0.01), at 24 h n = 3 (MA 18 vs 29.4 mm, P = 0.02; R-time: 9.4 vs 7.4 mins, P = 0.02; α-angle: 21.6 vs 26.5, P = 0.04 and FF: 168 vs 201 mg dL(-1) P = 0.01) and at 48 h n = 2 (MA: 29.7 vs 23.0, P = 0.02; R-time: 8.1 vs 6.7 mins, P = 0.05; α-angle: 22.6 vs 26.5, P = 0.04; FF: 170 vs 208 mg dL(-1), P = 0.01). There were no significant differences in TPC, APTT or PT between patients that bled and those that did not at each time point. CONCLUSIONS: Thrombocytopenic HM patients experiencing bleeding are hypocoaguable on TEG(®).

Controlled infection with a therapeutic virus defines the activation kinetics of human natural killer cells in vivo.

Human natural killer (NK) cells play an important role in anti-viral immunity. However, studying their activation kinetics during infection is highly problematic. A clinical trial of a therapeutic virus provided an opportunity to study human NK cell activation in vivo in a controlled manner. Ten colorectal cancer patients with liver metastases received between one and five doses of oncolytic reovirus prior to surgical resection of their tumour. NK cell surface expression of the interferon-inducible molecules CD69 and tetherin peaked 24-48 h post-infection, coincident with a peak of interferon-induced gene expression. The interferon response and NK cell activation were transient, declining by 96 h post-infection. Furthermore, neither NK cell activation nor the interferon response were sustained in patients undergoing multiple rounds of virus treatment. These results show that reovirus modulates human NK cell activity in vivo and suggest that this may contribute to any therapeutic effect of this oncolytic virus. Detection of a single, transient peak of activation, despite multiple treatment rounds, has implications for the design of reovirus-based therapy. Furthermore, our results suggest the existence of a post-infection refractory period when the interferon response and NK cell activation are blunted. This refractory period has been observed previously in animal models and may underlie the enhanced susceptibility to secondary infections that is seen following viral infection.

Gene expression profiling of Escherichia coli in response to interactions with the lettuce rhizosphere.

AIMS: The objective of this study was to examine transcriptional changes in Escherichia coli when the bacterium was growing in the lettuce rhizoshpere. METHODS AND RESULTS: A combination of microarray analyses, colonization assays and confocal microscopy was used to gain a more complete understanding of bacterial genes involved in the colonization and growth of E. coli K12 in the lettuce root rhizosphere using a novel hydroponic assay system. After 3 days of interaction with lettuce roots, E. coli genes involved in protein synthesis, stress responses and attachment were up-regulated. Mutants in curli production (crl, csgA) and flagella synthesis (fliN) had a reduced capacity to attach to roots as determined by bacterial counts and by confocal laser scanning microscopy. CONCLUSIONS: This study indicates that E. coli K12 has the capability to colonize lettuce roots by using attachment genes and can readily adapt to the rhizosphere of lettuce plants. SIGNIFICANCE AND IMPACT OF THE STUDY: Results of this study show curli production and biofilm modulation genes are important for rhizosphere colonization and may provide useful targets to disrupt this process. Further studies using pathogenic strains will provide additional information about lettuce-E. coli interactions.

Non-infectious orbital vasculitides.

Non-infectious vasculitides comprise a large number of diseases. Many of these diseases can cause inflammation within the orbit and a clinical presentation, which mimics numerous other processes. Orbital disease can often be the initial presentation of a systemic process and early diagnosis can help prevent long-term, potentially fatal consequences. The evaluation and treatment of non-infectious orbital vasculitides are often complicated and require a thorough understanding of the disease and underlying systemic associations. The long-term prognosis visually and systemically must be weighed against the risks and benefits of the treatment regimen. A large variety of corticosteroid formulations currently exist and are the mainstay of initial treatment. Traditional steroid-sparing immunosuppressive agents are also an important arsenal against these vasculitides. Recently, a new class of drugs called biologics, which target the various mediators of the inflammation cascade, may potentially provide more effective and less toxic treatment. This review aims to synthesize the current literature on non-infectious orbital vasculitides.

A microRNA gene expression signature predicts response to erlotinib in epithelial cancer cell lines and targets EMT.

BACKGROUND: Treatment with epidermal growth factor receptor (EGFR) inhibitors can result in clinical response in non-small-cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC) for some unselected patients. EGFR and KRAS mutation status, amplification of EGFR, or gene expression predictors of response can forecast sensitivity to EGFR inhibition. METHODS: Using an NSCLC cell line model system, we identified and characterised microRNA (miRNA) gene expression that predicts response to EGFR inhibition. RESULTS: Expression of 13 miRNA genes predicts response to EGFR inhibition in cancer cell lines and tumours, and discriminates primary from metastatic tumours. Signature genes target proteins that are enriched for epithelial-to-mesenchymal transition (EMT) genes. Epithelial-to-mesenchymal transition predicts EGFR inhibitor resistance and metastatic behaviour. The EMT transcription factor, ZEB1, shows altered expression in erlotinib-sensitive NSCLC and PDAC, where many signature miRNA genes are upregulated. Ectopic expression of mir-200c alters expression of EMT proteins, sensitivity to erlotinib, and migration in lung cells. Treatment with TGFß1 changes expression of signature miRNA and EMT proteins and modulates migration in lung cells. CONCLUSION: From these data, we hypothesise that the tumour microenvironment elicits TGFß1 and stimulates a miRNA gene expression program that induces resistance to anti-EGFR therapy and drives lung tumour cells to EMT, invasion, and metastasis.

Cdk-mediated phosphorylation of Chk1 is required for efficient activation and full checkpoint proficiency in response to DNA damage.

Here, we show that activation of the checkpoint effector kinase Chk1 in response to irradiation-induced DNA damage is minimal in G1, maximal during S-phase and diminishes as cells enter G2. In addition, formation of irradiation-induced replication protein A (RPA)-coated single-stranded DNA (RPA-ssDNA), a structure required for ATM and Rad3-related (ATR)-Chk1 activation, occurs in a broadly similar pattern. Cyclin-dependent kinase (Cdk) activity is thought to promote RPA-ssDNA formation by stimulating DNA strand resection at double-strand breaks (DSBs), providing one possible mechanism of imposing cell cycle dependence on DNA damage signaling. However, it has recently been shown that Chk1 itself is also subject to Cdk-mediated phosphorylation at serines 286 and 301 (S286 and 301). We show that Chk1 S301 phosphorylation increases as cells progress through S and G2 and that both Cdk1 and Cdk2 are likely to contribute to this modification in vivo. We also find that substitution of S286 and S301 with non-phosphorylatable alanine residues strongly attenuates DNA damage-induced Chk1 activation and G2 checkpoint proficiency, but does not eliminate the underlying cell cycle dependence of Chk1 regulation. Taken together, these data indicate that Cdk activity regulates multiple steps in the DNA damage response pathway including full activation of Chk1 and checkpoint proficiency.

A model-based assessment of the effects of projected climate change on the water resources of Jordan.

This paper is concerned with the quantification of the likely effect of anthropogenic climate change on the water resources of Jordan by the end of the twenty-first century. Specifically, a suite of hydrological models are used in conjunction with modelled outcomes from a regional climate model, HadRM3, and a weather generator to determine how future flows in the upper River Jordan and in the Wadi Faynan may change. The results indicate that groundwater will play an important role in the water security of the country as irrigation demands increase. Given future projections of reduced winter rainfall and increased near-surface air temperatures, the already low groundwater recharge will decrease further. Interestingly, the modelled discharge at the Wadi Faynan indicates that extreme flood flows will increase in magnitude, despite a decrease in the mean annual rainfall. Simulations projected no increase in flood magnitude in the upper River Jordan. Discussion focuses on the utility of the modelling framework, the problems of making quantitative forecasts and the implications of reduced water availability in Jordan.

Fate of Escherichia coli O157:H7 in ground beef following high-pressure processing and freezing.

AIMS: The purposes of this study were to evaluate the efficacy of high pressure to inactivate Escherichia coli O157:H7 in ground beef at ambient and subzero treatment temperatures and to study the fate of surviving bacteria postprocess and during frozen storage. METHODS AND RESULTS: Fresh ground beef was inoculated with a five-strain cocktail of E. coli O157:H7 vacuum-packaged, pressure-treated at 400 MPa for 10 min at -5 or 20 degrees C and stored at -20 or 4 degrees C for 5-30 days. A 3-log CFU g(-1) reduction of E. coli O157:H7 in the initial inoculum of 1 x 10(6) CFU g(-1) was observed immediately after pressure treatment at 20 degrees C. During frozen storage, levels of E. coli O157:H7 declined to <1 x 10(2) CFU g(-1) after 5 days. The physiological status of the surviving E. coli was affected by high pressure, sensitizing the cells to pH levels 3 and 4, bile salts at 5% and 10% and mild cooking temperatures of 55-65 degrees C. CONCLUSIONS: High-pressure processing (HPP) reduced E. coli O157:H7 in ground beef by 3 log CFU g(-1) and caused substantial sublethal injury resulting in further log reductions of bacteria during frozen storage. SIGNIFICANCE AND IMPACT OF THE STUDY: HPP treatment of packaged ground beef has potential in the meat industry for postprocess control of pathogens such as E. coli O157:H7 with enhanced safety of the product.