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Stable isotope‐based reconstructions of past ocean salinity and hydroclimate depend on accurate, regionally constrained relationships between the stable oxygen isotopic composition of seawater (δ18Osw) and salinity in the surface ocean. An increasing number of δ18Osw observations suggest greater spatial variability in this relationship than previously considered, highlighting the need to reassess these relationships on a global scale. Here, we use available, paired δ18Osw and salinity data (N = 11,119) to create global interpolations of each variable. We then use a self‐organizing map, a specialized form of machine learning, to define 19 regions with unique δ18Osw‐salinity relationships in the surface (<50 m) ocean. Inclusion of atmospheric moisture‐related variables and oceanic tracer data in additional self‐organizing map experiments indicates global surface δ18Osw‐salinity spatial patterns are strongly forced by the atmosphere, as the SOM spatial output is highly similar despite no overlapping input data. Our approach is a useful update to the previously delimited regions, and highlights the utility of neural network pattern extraction in spatiotemporally sparse data sets. Plain Language Summary: Our understanding of past changes in the ocean and atmosphere often comes from information stored in biological marine carbonate archives. Stable oxygen isotope measurements from such archives record past ocean temperature as well as the stable oxygen isotopic composition of seawater. In the surface ocean, stable oxygen isotope values have a strong, linear, relationship with salinity, thought to be the result of evaporation and precipitation affecting stable isotope ratios and salinity in a similar manner. This permits reconstruction of past ocean salinity from marine carbonates, which may be used to infer large‐scale hydroclimate variability, in some cases. However, this manner of reconstruction relies on the linear isotope‐salinity relationship, which remains poorly constrained and is influenced by a combination of oceanic and atmospheric processes. In this work, we define regional isotope‐salinity relationships and broadly assess whether ocean or atmospheric processes play a larger role in the spatial distribution of these regions. We identify new regions compared to previous work, and find that over most of the ocean, precipitation, precipitation isotope values, and evaporation are important in setting seawater isotope‐salinity patterns. Key Points: Mixed‐layer regions with distinct salinity‐seawater δ18O paired values are identified by self‐organizing mapInclusion of atmospheric or oceanic tracers in the self‐organizing map shifts the spatial distribution of salinity‐seawater δ18O patternsRegion identification is still dependent on available observational data, but the throughput offered here enables updating as data increase [ABSTRACT FROM AUTHOR]

A model that takes into account the current workload, and the workload the athlete has been prepared for, as an acute:chronic workload ratio has been previously used as a novel way to monitor training load and injury risk. Fifty-nine elite Australian football players from one club participated in this 2-year study. Global Positioning System technology was used to provide information on running workloads of players. An injury was defined as any non-contact 'time-loss' injury. One-week (acute), along with 4-week (chronic) workloads were calculated for a range of variables. The size of the acute workload in relation to the chronic workload was calculated as an acute:chronic workload ratio. An acute:chronic workload ratio of >2.0 for total distance during the in-season was associated with a 5 to 8-fold greater injury risk in the current [relative risk ( RR) = 8.65, P = 0.001] and subsequent week ( RR = 5.49, P = 0.016). Players with a high-speed distance acute:chronic workload ratio of >2.0 were 5-11 times more likely to sustain an injury in the current ( RR = 11.62, P = 0.006) and subsequent week ( RR = 5.10, P = 0.014). These findings demonstrate that sharp increases in running workload increase the likelihood of injury in both the week the workload is performed, and the subsequent week. [ABSTRACT FROM AUTHOR]

Insecticide-treated clothing has been used for many years by the military and in recreational activities as personal protection against bites from a variety of arthropods including ticks, chigger mites, sandflies and mosquitoes. Permethrin is the most commonly used active ingredient, but others, including bifenthrin, deltamethrin, cyfluthrin, DEET (N,N-diethyl-3-methylbenz-amide) and KBR3023, have also been trialled. Treatment is usually carried out by home or factory dipping. However, new microencapsulation technologies which may prolong the activity of insecticides on clothing are now available and may help to overcome the inevitable reduction in efficacy over time that occurs as a result of washing, ultraviolet light exposure, and the normal wear and tear of the fabric. The aim of this article is to review the evidence base for the use of insecticide-treated clothing for protection against bites from arthropods and its effect on arthropod-borne pathogen transmission. Although some studies do demonstrate protection against pathogen transmission, there are surprisingly few, and the level of protection provided varies according to the disease and the type of study conducted. For example, insecticide-treated clothing has been reported to give between 0% and 75% protection against malaria and between 0% and 79% protection against leishmaniasis. Studies vary in the type of treatment used, the age group of participants, the geographical location of the study, and the pathogen transmission potential. This makes it difficult to compare and assess intervention trials. Overall, there is substantial evidence that insecticide-treated clothing can provide protection against arthropod bites. Bite protection evidence suggests that insecticide-treated clothing may be useful in the prevention of pathogen transmission, but further investigations are required to accurately demonstrate transmission reduction. [ABSTRACT FROM AUTHOR]

BACKGROUND Since 2002, priority Model for End-stage Liver Disease (MELD) exception status has been given to patients with hepatocellular carcinoma (HCC) who meet the Milan criteria. Since then, the number of liver transplantations performed in patients with HCC has increased, but to the authors' knowledge, few studies to date have examined the effect of MELD exception recommendations on therapy use and survival rates in a nationwide sample. The current study examines therapy use and long-term survival rates among patients with HCC tumors meeting the Milan criteria in the post-MELD exception era. METHODS The current study is a retrospective cohort study of 2179 patients with localized HCC meeting the Milan criteria who were registered between 2004 and 2007 in the Surveillance, Epidemiology, and End Results database. RESULTS A total of 43% of patients did not receive any specific therapy. Overall, the 5-year relative survival rate for patients receiving only supportive care was dismal at 24% (95% confidence interval [95% CI], 21%-27%), whereas that for patients undergoing liver transplantation was 77% (95% CI, 71%-82%). Long-term survival was found to be dependent on age, race/ethnicity, and type of therapy received. A multivariate Cox proportional hazards model adjusted for age, race/ethnicity, and type of therapy received demonstrated that, compared with white patients, black patients had significantly poorer survival outcomes (hazards ratio, 1.23; 95% CI, 1.03-1.47 [ P = .02]), whereas Asian/Pacific Islander patients had significantly better survival rates when compared with white patients (HR, 0.66; 95% CI, 0.57-0.77 [ P < .001]). CONCLUSIONS Despite having localized disease that met transplantation criteria, nearly 50% of the large nationwide cohort of patients with HCC in the current study received only supportive care and had dismal 5-year relative survival rates, especially among black patients. Cancer 2014;120:1725-1732. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

Aim Rubber band ligation is a common office procedure for the treatment of symptomatic haemorrhoids. It can be associated with pain and vasovagal symptoms. The effect of local anaesthetic use during banding was studied. Method A single-blinded randomized controlled trial was carried out in the colorectal outpatient clinic. Patients presenting with symptomatic haemorrhoids suitable for banding were prospectively recruited and randomized to undergo the procedure with local anaesthetic or without (control). Submucosal bupivacaine was injected immediately after banding just proximal to the site. Vasovagal symptoms were assessed at the time of banding and pain scores (visual analogue scale) were recorded at the conclusion of the procedure, after 15 min, and on leaving the clinic. Results Seventy-two patients (40 local anaesthetic injection, group 1; 32 no injection, group 2) were recruited. The mean ages were 50 and 54 years respectively, the median duration of symptoms was 12 months in each group and the median number of haemorrhoids banded was three in each group. The mean pain score on leaving the clinic was 2.6 (95% CI 2.1, 3.1) in group 1 and 4.1 (95% CI 3.3, 5.0) ( P = 0.04) in group 2. There were no complications related to local anaesthetic use. No significant difference in vasovagal symptoms was found ( P = 0.832). Conclusion Local anaesthetic injection at the time of banding is simple and safe. It may reduce patient discomfort following banding of haemorrhoids. [ABSTRACT FROM AUTHOR]

Early predictors of prognosis in Guillain-Barré syndrome (GBS) are needed to identify patients who are likely to make a poor recovery and to guide therapeutic decision-making in the acute phase. Here we investigate whether axonal protein biomarkers released into the cerebrospinal fluid (CSF) following proximal axonal damage improve the early prognostic accuracy in GBS. A prospective multicenter study including 132 patients (38 GBS, 38 neurological controls, 42 headaches, 14 chronic inflammatory demyelinating neuropathy). CSF levels of axonal [neurofilament (NfH) and tau] and glial (S100B and glial fibrillary acidic protein) protein biomarkers were measured on admission. Nerve conduction studies were performed at the time of lumbar puncture and patients were classified according to neurophysiological criteria. Outcome was assessed on the Hughes functional score (F-score). Poor outcome was defined as the inability to walk independently (F-score > or = 3). High NfH levels (>0.73 ng/ml) predicted poor outcome (P = 0.01) with an odds ratio of 7.3 and correlated with the outcome F-score (R = 0.51, P < 0.01), as did hTau levels (R = 0.47, P < 0.01). Patients with poor outcome had significantly higher CSF NfH (median 1.78 ng/ml) when compared to those with good outcome (0.03 ng/ml) or all of the control groups (neurological controls 0.18 ng/ml, headaches 0.06 ng/ml, chronic inflammatory demyelinating neuropathy 0.05 ng/ml). Except for age (P < 0.05) and need for ventilatory support (P < 0.05), none of the other features reliably predicted outcome. Improved prognostic accuracy in the acute phase of GBS seems possible using CSF NfH levels. [ABSTRACT FROM AUTHOR]

4-Diphosphocytidyl-2 C-methyl-d-erythritol kinase (IspE) catalyses the ATP-dependent conversion of 4-diphosphocytidyl-2 C-methyl-d-erythritol (CDPME) to 4-diphosphocytidyl-2 C-methyl-d-erythritol 2-phosphate with the release of ADP. This reaction occurs in the non-mevalonate pathway of isoprenoid precursor biosynthesis and because it is essential in important microbial pathogens and absent from mammals it represents a potential target for anti-infective drugs. We set out to characterize the biochemical properties, determinants of molecular recognition and reactivity of IspE and report the cloning and purification of recombinant Aquifex aeolicus IspE ( AaIspE), kinetic data, metal ion, temperature and pH dependence, crystallization and structure determination of the enzyme in complex with CDP, CDPME and ADP. In addition, 4-fluoro-3,5-dihydroxy-4-methylpent-1-enylphosphonic acid (compound 1) was designed to mimic a fragment of the substrate, a synthetic route to 1 was elucidated and the complex structure determined. Surprisingly, this ligand occupies the binding site for the ATP α-phosphate not the binding site for the methyl-d-erythritol moiety of CDPME. Gel filtration and analytical ultracentrifugation indicate that AaIspE is a monomer in solution. The enzyme displays the characteristic α/β galacto-homoserine-mevalonate-phosphomevalonate kinase fold, with the catalytic centre positioned in a deep cleft between the ATP- and CDPME-binding domains. Comparisons indicate a high degree of sequence conservation on the IspE active site across bacterial species, similarities in structure, specificity of substrate recognition and mechanism. The biochemical characterization, attainment of well-ordered and reproducible crystals and the models resulting from the analyses provide reagents and templates to support the structure-based design of broad-spectrum antimicrobial agents. [ABSTRACT FROM AUTHOR]

We made observations from vertical moorings of thermistors and current meters in Lake Ontario to study the spring thermal bar circulation, its effect in inhibiting the horizontal mixing, and spatial and temporal variability of vertical mixing during this period. Thermal bar progression rates were compared with two analytical models; both produced overestimates during the early part of the thermal bar and underestimates during the late spring. In a zone between the shore and the thermal bar, currents were influenced by the local wind stress and flowed in a counterclockwise direction. The mean cross-shore flows in the nearshore zone were reduced during the thermal bar period. The alongshore horizontal exchange coefficients were higher than cross-shore exchange coefficients. During the thermal bar period, the magnitude of both alongshore and cross-shore exchange coefficients decreased when the bar was still within middepth (<40 m); when it was further offshore, the thermal bar did not have any significant effect on alongshore exchange coefficients, but cross-shore exchanges decreased marginally. The vertical exchange coefficients were high in the water column because of convective mixing during the thermal bar period. During the evolution of spring thermal bar, the vertical mixing decreased considerably in the nearshore regions under stable stratification, whereas the high vertical mixing levels continued in the offshore region for a longer period. [ABSTRACT FROM AUTHOR]

To determine whether the offering of a consumer-directed health plan (CDHP) is likely to cause risk segmentation in an employer group. The study population comprises the approximately 10,000 people (employees and dependents) enrolled as members of the employee health benefit program of Humana Inc. at its headquarters in Louisville, Kentucky, during the benefit years starting July 1, 2000, and July 1, 2001. This analysis is based on primary collection of claims, enrollment, and employment data for those employees and dependents. This is a case study of the experience of a single employer in offering two consumer-directed health plan options (“Coverage First 1” and “Coverage First 2”) to its employees. We assessed the risk profile of those choosing the Coverage First plans and those remaining in more traditional health maintenance organization (HMO) and preferred provider organization (PPO) coverage. Risk was measured using prior claims (in dollars per member per month), prior utilization (admissions/1,000; average length of stay; prescriptions/1,000; physician office visit services/1,000), a pharmacy-based risk assessment tool (developed by Ingenix), and demographics. Complete claims and administrative data were provided by Humana Inc. for the two-year study period. Unique identifiers enabled us to track subscribers' individual enrollment and utilization over this period. Based on demographic data alone, there did not appear to be a difference in the risk profiles of those choosing versus not choosing Coverage First. However, based on prior claims and prior use data, it appeared that those who chose Coverage First were healthier than those electing to remain in more traditional coverage. For each of five services, prior-year usage by people who subsequently enrolled in Coverage First 1 (CF1) was below 60 percent of the average for the whole group. Hospital and maternity admissions per thousand were less than 30 percent of the overall average; length of stay per hospital admission, physician office services per thousand, and prescriptions per thousand were all between 50 and 60 percent of the overall average. Coverage First 2 (CF2) subscribers' prior use of services was somewhat higher than CF1 subscribers', but it was still below average in every category. As with prior use, prior claims data indicated that Coverage First subscribers were healthier than average, with prior total claims less than 50 percent of average. In this case, the offering of high-deductible or consumer-directed health plan options alongside more traditional options caused risk segmentation within an employer group. The extent to which these findings are applicable to other cases will depend on many factors, including the employer premium contribution policies and employees' perception of the value of the various plan options. Further research is needed to determine whether risk segmentation will worsen in future years for this employer and if so, whether it will cause premiums for more traditional health plans to increase. [ABSTRACT FROM AUTHOR]

Phlebotomy-induced anaemia excepted, thrombocytopenia is the most common haematological abnormality in neonatal intensive care unit (NICU) patients. Roughly one-quarter of all NICU patients and half of all sick preterm neonates develop thrombocytopenia. Whereas a large number of varied precipitating conditions has been identified, early-onset thrombocytopenia (<72 h) is most commonly associated with fetomaternal conditions complicated by placental insufficiency and/or fetal hypoxia, e.g. maternal pre-eclampsia and fetal intrauterine growth restriction. The resulting neonatal thrombocytopenia is usually mild to moderate, resolves spontaneously and requires no specific therapy. Deviation from this pattern of thrombocytopenia suggests the presence of more significant precipitating conditions. The most important of these are the immune thrombocytopenias, and every NICU should develop investigation and treatment protocols to manage these cases promptly and avoid unnecessary risk of haemorrhage. In contrast, late-onset thrombocytopenia (>72 h) is almost always associated with sepsis or necrotizing enterocolitis and the associated thrombocytopenia is severe, prolonged and often requires treatment by platelet transfusion. Unfortunately, evidence-based guidelines for platelet transfusion therapy in NICU patients are currently unavailable, making it difficult to define widely accepted thresholds for transfusion and leading to a significant variation in transfusion practice between centres. Conclusion: While improving this situation remains a pressing need, the growing evidence that impaired megakaryocytopoiesis and platelet production are major contributors to many neonatal thrombocytopenias suggests that recombinant haemopoietic growth factors, including thrombopoietin and interleukin-11, may be useful future therapies to ameliorate neonatal thrombocytopenia. [ABSTRACT FROM AUTHOR]

Summary Platelet transfusions are frequently given to neonatal intensive care unit (NICU) patients with severe thrombocytopenia (platelets less than 50 × 109 L-1 ) but no study has assessed whether this is clinically appropriate. To address this we conducted a retrospective review of platelet transfusion practice in patients developing severe thrombocytopenia over 3 years in a single NICU. Out of 901 admissions, 53 (6%) developed severe thrombocytopenia. Twenty-seven neonates received a total of 63 platelet transfusions, the main triggers being: platelet count less than 30 × 109 L-1 (all patients), or less than 50 × 109 L-1 in those with previous haemorrhage or clinical instability. No major haemorrhage occurred during severe thrombocytopenia either in neonates in whom platelet transfusions were withheld (26/53) or in neonates given platelets who survived to discharge (22/27). Five preterm neonates given platelets died but all had overwhelming sepsis or necrotizing enterocolitis and none died directly as a result of haemorrhage. Although the widely used liberal triggers for neonatal platelet transfusion highlighted in this review reflect available guidelines, and represent cautious (‘safe’) haemostatic practice, they are likely to result in unnecessary transfusion for a significant number of NICU patients. Improved practice requires definition of a safe lower limit for platelet count in stable neonates; effective platelet transfusion strategies for sick neonates; and improved therapies for conditions precipitating severe thrombocytopenia. [ABSTRACT FROM AUTHOR]

Features the Puffer-patient-controlled analgesia device from Graseby PLC. Key features and functionality; Inventiveness of the design of the medical device; Advantages of using in pain management.

Abstract The mountain pygmy-possum, Burramys parvus, exists in isolated and fragmented populations in the Australian alps. To examine the degree of interpopulation divergence, mitochondrial cytochrome b and NADH dehydrogenase subunit 2 (NADH2) sequences were obtained from samples representing all populations of B. parvus. Three divergent mitochondrial DNA (mtDNA) lineages were identified which exhibited strong phylogeographical structure. This indicates the presence of three maternal clades corresponding to populations in the northern, central and southern Australian alps. Molecular clock estimates suggest that the mtDNA lineages diverged from one another 420–680 thousand years ago. On this basis it is argued that B. parvus populations have probably been isolated since the mid-Pleistocene, and that management should focus on maintaining viable B. parvus populations in each of the three regional localities. [ABSTRACT FROM AUTHOR]

Twenty-three patients who had myelofibrosis with myeloid metaplasia (MMM) were treated at our institution with 50 courses of splenic irradiation (SI) for symptomatic splenomegaly. The median dose of radiation per course was 277.5 cGy, administered in a median of 7.5 fractions. 8/23 patients received multiple courses of SI. Of 49 evaluable courses of SI, 46 (93.9%) resulted in an objective decrease in spleen size. The median duration of response was 6 months (range 1–41). Reduction in spleen size was associated with symptomatic relief in all patients. Overall median survival after SI was 22 months. Significant cytopenia occurred in 10 (43.5%) patients, or 16 (32%) of the 50 courses of SI. Prolonged, life-threatening pancytopenia after a single course of SI occurred in six patients (26%), resulting in fatal sepsis or haemorrhage in three (13%). Nine patients underwent subsequent splenectomy; the perioperative mortality rate was 11%. One third of patients experienced postoperative intra-abdominal haemorrhage necessitating surgical re-exploration. SI can provide symptomatic relief and a reduction in spleen size in most MMM patients. The increased risk of postoperative bleeding in patients requiring subsequent splenectomy dictates against considering SI as an alternative to splenectomy for patients who are otherwise good surgical candidates. [ABSTRACT FROM AUTHOR]

This paper describes development of Padres Trabajando por la Paz, a violence prevention intervention for Hispanic parents to increase parental monitoring. The intervention was developed using an innovative new program planning process: intervention mapping. Theory and empirical evidence broadly defined performance objectives and determinants of parental monitoring. These objectives were further refined through group and individual interviews with the target parent group. Learning objectives for the intervention guided the content of the intervention that used modeling as the primary method and role model stories as a strategy delivered through newsletters. Stage-matching members of the target population for their readiness to implement the parental monitoring behaviors further refined the social cognitive message design strategies. Intervention mapping provides an explicit theory- and data-driven guide for intervention development that maximizes intervention impact for a specific target population. [ABSTRACT FROM AUTHOR]

Predation by the red fox Vulpes vulpes is believed to be threatening the little penguin Eudyptula minor on Phillip Island in Victoria. Polymorphism at seven microsatellite loci was examined to estimate the extent of differentiation between Phillip Island and mainland populations of V. vulpes. Loss of alleles has occurred on Phillip Island where foxes first appeared = 88 years ago compared with mainland populations. Genetic differentiation between the Phillip Island and mainland populations was high. The relatively high differentiation found between the two populations could be due to either low migration rates, the effect of the composition of founder animals or both effects. Further ecological and historical information about the populations is needed to explore the likely significance of these effects. [ABSTRACT FROM AUTHOR]

The audiologic performance of 54 postlingually deafened adults wearing cochlear implants was uniformly evaluated. The participants had 9 months' or more experience with one of five different cochlear prostheses (Los Angeles Single Channel (N = 11), Vienna Single Channel (N = 4), Melbourne Multichannel (N = 18), Utah Multichannel (N = 19), San Francisco Multichannel (N = 2). The multichannel designs enabled participants to recognize more environmental sounds, provided more speech reading enhancement, and enabled most users to understand limited speech in the sound-only condition, compared to the single-channel implant group. [ABSTRACT FROM AUTHOR]

Type I restriction enzymes comprise three subunits only one of which, the S polypeptide, dictates the specificity of the DNA sequence recognized. Recombination between two different hsdS genes, SP and SB, led to the isolation of a system, SQ, which had a different specificity from that of either parent. The finding that the nucleotide sequence recognized by SO is a hybrid containing components from both the SP and SB target sequences suggested that DNA recognition is carried out by two separable domains within each specificity polypeptide. To test this we have made the recombinant gene of reciprocal structure and demonstrate that it encodes a polypeptide whose recognition sequence, deduced in vivo, is as predicted by this model. We also report the sequence of the SB specificity gene, so that information is now available for the five known members of this family of enzymes. All show a similar organization of conserved and variable regions. Comparisons of the predicted amino acid sequences reveal large non-conserved areas which may not even be structurally similar. This is remarkable since these different S subunits are functionally identical, except for the specificity with respect to the DNA sequence with which they interact. We discuss the correlation of the variation in polypeptide sequence with recognition specificities. [ABSTRACT FROM AUTHOR]