Epidemiology of healthcare-associated infection reported from a hospital-wide incidence study: considerations for infection prevention and control planning.

BACKGROUND: The measure of disease frequency most widely used to report healthcare-associated infection (HAI) is the point-prevalence survey. Incidence studies are rarely performed due to time and cost constraints; they show which patients are affected by HAI, when and where, and inform planning and design of infection prevention and control (IPC) measures. AIM: To determine the epidemiology of HAI within a general and a teaching hospital in Scotland. METHODS: A prospective observational incidence study was undertaken for one year from April 2018 using data collected as part of the Evaluation of Cost of Nosocomial Infection (ECONI) study. A novel, robust approach was undertaken, using record linkage to national administrative data to provide full admission and discharge information. Cases were recorded if they met international HAI definitions. FINDINGS: Incidence of HAI for the combined hospitals was 250 HAI cases per 100,000 acute occupied bed-days (AOBD). Highest frequency was in urinary tract (51.2 per 100,000 AOBD), bloodstream (44.7), and lower respiratory tract infection (42.2). The most frequently reported organisms were Escherichia coli, Staphylococcus aureus, and norovirus. Incidence of HAI was higher in older people and emergency cases. There was an increase in the rate of HAI in summer months (pneumonia, respiratory, surgical, and gastrointestinal infection) and in winter months norovirus gastrointestinal infection (P < 0.0001). The highest incidence specialties were intensive care, renal medicine, and cardiothoracic surgery. HAI occurred at a median of 9 days (interquartile range: 4-19) after admission. Incidence data were extrapolated to provide an annual national estimate of HAI in NHS Scotland of 7437 (95% confidence interval: 7021-7849) cases. CONCLUSION: This study provides a unique overview of incidence of HAI and identifies the burden of HAI at the national level for the first time. Understanding the incidence in different clinical settings, at different times, will allow targeting of IPC measures to those patients who would benefit the most.

Impact of healthcare-associated infection on length of stay.

BACKGROUND: Increased length of stay (LOS) for patients is an important measure of the burden of healthcare-associated infection (HAI). AIM: To estimate the excess LOS attributable to HAI. METHODS: This was a one-year prospective incidence study of HAI observed in one teaching hospital and one general hospital in NHS Scotland as part of the Evaluation of Cost of Nosocomial Infection (ECONI) study. All adult inpatients with an overnight stay were included. HAI was diagnosed using European Centres for Disease Prevention and Control definitions. A multi-state model was used to account for the time-varying nature of HAI and the competing risks of death and discharge. FINDINGS: The excess LOS attributable to HAI was 7.8 days (95% confidence interval (CI): 5.7-9.9). Median LOS for HAI patients was 30 days and for non-HAI patients was 3 days. Using a simple comparison of duration of hospital stay for HAI cases and non-cases would overestimate the excess LOS by 3.5 times (27 days compared with 7.8 days). The greatest impact on LOS was due to pneumonia (16.3 days; 95% CI: 7.5-25.2), bloodstream infections (11.4 days; 5.8-17.0) and surgical site infection (SSI) (9.8 days; 4.5-15.0). It is estimated that 58,000 bed-days are occupied due to HAI annually. CONCLUSION: A reduction of 10% in HAI incidence could make 5800 bed-days available. These could be used to treat 1706 elective patients in Scotland annually and help reduce the number of patients awaiting planned treatment. This study has important implications for investment decisions in infection prevention and control interventions locally, nationally, and internationally.

Personalized infection prevention and control: identifying patients at risk of healthcare-associated infection.

BACKGROUND: Few healthcare-associated infection (HAI) studies focus on risk of HAI at the point of admission. Understanding this will enable planning and management of care with infection prevention at the heart of the patient journey from the point of admission. AIM: To determine intrinsic characteristics of patients at hospital admission and extrinsic events, during the two years preceding admission, that increase risk of developing HAI. METHODS: An incidence survey of adults within two hospitals in NHS Scotland was undertaken for one year in 2018/19 as part of the Evaluation of Cost of Nosocomial Infection (ECONI) study. The primary outcome measure was developing any HAI using recognized case definitions. The cohort was derived from routine hospital episode data and linkage to community dispensed prescribing data. FINDINGS: The risk factors present on admission observed as being the most significant for the acquisition of HAI were: being treated in a teaching hospital, increasing age, comorbidities of cancer, cardiovascular disease, chronic renal failure and diabetes; and emergency admission. Relative risk of developing HAI increased with intensive care unit, high-dependency unit, and surgical specialties, and surgery <30 days before admission and a total length of stay of >30 days in the two years to admission. CONCLUSION: Targeting patients at risk of HAI from the point of admission maximizes the potential for prevention, especially when extrinsic risk factors are known and managed. This study proposes a new approach to infection prevention and control (IPC), identifying those patients at greatest risk of developing a particular type of HAI who might be potential candidates for personalized IPC interventions.

Bed-days and costs associated with the inpatient burden of healthcare-associated infection in the UK.

BACKGROUND: Healthcare-associated infection (HAI) is associated with increased morbidity and mortality resulting in excess costs. AIM: To investigate the impact of all types of HAI on the inpatient cost of HAI using different approaches. METHODS: The incidence, types of HAI, and excess length of stay were estimated using data collected as part of the Evaluation of Cost of Nosocomial Infection (ECONI) study. Scottish NHS reference costs were used to estimate unit costs for bed-days. Variable (cash) costs associated with infection prevention and control (IPC) measures and treatment were calculated for each HAI type and overall. The inpatient cost of HAI is presented in terms of bed-days lost, bed-day costs, and cash costs. FINDINGS: In Scotland 58,010 (95% confidence interval: 41,730-74,840) bed-days were estimated to be lost to HAI during 2018/19, costing £46.4 million (19m-129m). The total annual cost in the UK is estimated to be £774 million (328m-2,192m). Bloodstream infection and pneumonia were the most costly HAI types per case. Cash costs are a small proportion of the total cost of HAI, contributing 2.4% of total costs. CONCLUSION: Reliable estimates of the cost burden of HAI management are important for assessing the cost-effectiveness of IPC programmes. This unique study presents robust economic data, demonstrating that HAI remains a burden to the UK NHS and bed-days capture the majority of inpatient costs. These findings can be used to inform the economic evaluation and decision analytic modelling of competing IPC programmes at local and national level.

Evaluating the post-discharge cost of healthcare-associated infection in NHS Scotland.

BACKGROUND: Whereas the cost burden of healthcare-associated infection (HAI) extends beyond the inpatient stay into the post-discharge period, few studies have focused on post-discharge costs. AIM: To investigate the impact of all types of HAI on the magnitude and distribution of post-discharge costs observed in acute and community services for patients who developed HAI during their inpatient stay. METHODS: Using data from the Evaluation of Cost of Nosocomial Infection (ECONI) study and regression methods, this study identifies the marginal effect of HAI on the 90-daypost-discharge resource use and costs. To calculate monetary values, unit costs were applied to estimates of excess resource use per case of HAI. FINDINGS: Post-discharge costs increase inpatient HAI costs by 36%, with an annual national cost of £10,832,437. The total extra cost per patient with HAI was £1,457 (95% confidence interval: 1,004-4,244) in the 90 days post discharge. Patients with HAI had longer LOS if they were readmitted and were prescribed more antibiotics in the community. The results suggest that HAI did not have an impact on the number of readmissions or repeat surgeries within 90 days of discharge. The majority (95%) of the excess costs was on acute care services after readmission. Bloodstream infection, gastrointestinal infection, and pneumonia had the biggest impact on post-discharge cost. CONCLUSION: HAI increases costs and antibiotic consumption in the post-discharge period. Economic evaluations of IPC studies should incorporate post-discharge costs. These findings can be used nationally and internationally to support decision-making on the impact of IPC interventions.

The efficacy of three on-farm euthanasia methods for broiler chickens throughout the production cycle.

1. There is a need to humanely kill moribund or injured broiler birds on-farm with no reasonable chance of recovery. Two experiments evaluated the efficacy of three commercially applicable killing methods; manual cervical dislocation (CD), mechanical cervical dislocation with the Koechner Euthanising Device (KED) and a non-penetrative captive bolt device (Zephyr-EXL; ZEXL), at 7, 21 or 35 d of age, on their ability to induce insensibility (unconsciousness and loss of brain stem reflexes) and death.2. Experiment one assessed the damage to the cranial-cervical region resulting from the methods applied to cadavers of cull birds (n = 180) by radiography and gross pathology observation.3. Experiment two evaluated the latency to insensibility and death when cull broiler birds (n = 240) were killed by CD, KED or ZEXL, using behavioural and reflexive indicators. Insensibility and death were measured by the absence of pupillary light, palpebral blink and nictitating membrane reflexes and cessation of rhythmic breathing, cloacal winking and convulsions. Analysis of variance for the main effect of the method was performed to determine the differences.4. In experiment one, only the Zephyr resulted in skull fractures. A higher number of vertebral fractures occurred with KED application compared to CD, at 21 and 35 d.5. In experiment two, indicators of sensibility were absent earliest with the ZEXL (µ < 2 s); then,CD (µ = 28 s) and were longest with KED (µ = 47 s), at 21 and 35 d. Cloacal winking and convulsions ceased earlier after CD (88 s), compared to either KED (124 s) or Zephyr (118 s). Death after a single application occurred 100%, 100% and 98% of time for CD, KED and ZEXL, respectively.6. Overall, all methods were efficacious at inducing insensibility and death. Insensibility occurred earliest with ZEXL, whilst death occurred earliest with CD. KED resulted in the longest time to insensibility and death.

Assessing the effect of water deprivation on the efficacy of on-farm euthanasia methods for broiler chickens.

1. Moribund or diseased poultry requiring euthanasia are often dehydrated. To understand how dehydration influences the efficacy of various killing methods, this experiment investigated the effect of water deprivation (WD) on times to unconsciousness and death.2. Broiler chickens (n = 179) were water-deprived for 0, 24, 48 or 72 hours to mimic dehydration, then killed via manual cervical dislocation, mechanical cervical dislocation (Koechner Euthanising Device (KED)), or non-penetrating captive bolt (Zephyr-EXL), at 8, 22, 36 or 50 d of age. Degree of WD was confirmed by skin turgor, packed cell volume and body weight loss. Method efficacy was evaluated by the time to unconsciousness and death using pupillary light (PUP), palpebral blink (PAL) and nictitating membrane (NIC) reflexes, feather erection (FE), cloacal winking (CW) and convulsions (CN). The extent of damage caused by each method was examined via radiography, gross pathology and histopathology. The main effects of WD time and euthanasia method were analysed by two-way analyses of variance (CRD, PROC MIXED, SAS 9.4) with a-priori contrasts to compare water-deprived versus non-water-deprived (NON) birds.3. Skin turgor, packed cell volume and body weight loss had a quadratic relationship with WD, with highest values for those birds which were water-deprived for 72 h. WD level did not affect time to unconsciousness. Time to death was longer for WD birds than NON, with longer latencies to FE, CW and CN for water-deprived birds. WD only affected radiography or gross pathology scores on d 8, with the extent of subcutaneous haemorrhage within the neck decreasing as WD increased.4. The shortest latency to PUP loss, at all ages, and to PAL and NIC loss, at 22 d, was with the Zephyr-EXL. KED had the longest time to unconsciousness (PUP, PAL and NIC), at all ages, and to death, at 36 and 50 d.5. Overall, WD increased time to death, but did not affect the onset of unconsciousness, with no interaction between methods and WD level.

Kyasanur Forest disease virus non-mouse animal models: a pilot study.

OBJECTIVES: Mouse models have delivered variable recapitulation of Kyasanur Forest disease (KFD) pathology and consistently demonstrated neurological involvement which may be a limited feature of human disease. With the purpose of more accurately modelling human disease progression we infected several small-mammalian models: guinea pigs, hamsters and ferrets with a titered infectious dose of Kyasanur Forest disease virus (KFDV). Clinical indicators of disease severity were observed for seventeen days, on day eighteen a visual post-mortem analysis of visceral organs was conducted. Viral load in selected tissues was measured to infer disease signs and the establishment of viral replication. DATA DESCRIPTION: Daily monitoring did not reveal any observable signs of illness; weight loss was minimal across species and gross pathology did not indicate severe viral infection. Tissue specific tropism and establishment of viral infection was monitored by quantitative real-time polymerase chain reaction (qRT-PCR). No viral replication was detected in ferrets (n = 0/3), but was present in the spleen of guinea pigs (n = 3/3) and the brain of hamsters (n = 3/3). Low levels of viral RNA were detected in multiple hamster tissues (kidney, liver, lung and spleen) suggesting the possibility of viral tropism and possible adaptation to the host. No serological tests were performed.

How do climate change experiments alter plot-scale climate?

To understand and forecast biological responses to climate change, scientists frequently use field experiments that alter temperature and precipitation. Climate manipulations can manifest in complex ways, however, challenging interpretations of biological responses. We reviewed publications to compile a database of daily plot-scale climate data from 15 active-warming experiments. We find that the common practices of analysing treatments as mean or categorical changes (e.g. warmed vs. unwarmed) masks important variation in treatment effects over space and time. Our synthesis showed that measured mean warming, in plots with the same target warming within a study, differed by up to 1.6  ∘ C (63% of target), on average, across six studies with blocked designs. Variation was high across sites and designs: for example, plots differed by 1.1  ∘ C (47% of target) on average, for infrared studies with feedback control (n = 3) vs. by 2.2  ∘ C (80% of target) on average for infrared with constant wattage designs (n = 2). Warming treatments produce non-temperature effects as well, such as soil drying. The combination of these direct and indirect effects is complex and can have important biological consequences. With a case study of plant phenology across five experiments in our database, we show how accounting for drier soils with warming tripled the estimated sensitivity of budburst to temperature. We provide recommendations for future analyses, experimental design, and data sharing to improve our mechanistic understanding from climate change experiments, and thus their utility to accurately forecast species' responses.

Automated symptom and treatment side effect monitoring for improved quality of life among adults with diabetic peripheral neuropathy in primary care: a pragmatic, cluster, randomized, controlled trial.

AIMS: To evaluate the effectiveness of automated symptom and side effect monitoring on quality of life among individuals with symptomatic diabetic peripheral neuropathy. METHODS: We conducted a pragmatic, cluster randomized controlled trial (July 2014 to July 2016) within a large healthcare system. We randomized 1834 primary care physicians and prospectively recruited from their lists 1270 individuals with neuropathy who were newly prescribed medications for their symptoms. Intervention participants received automated telephone-based symptom and side effect monitoring with physician feedback over 6 months. The control group received usual care plus three non-interactive diabetes educational calls. Our primary outcomes were quality of life (EQ-5D) and select symptoms (e.g. pain) measured 4-8 weeks after starting medication and again 8 months after baseline. Process outcomes included receiving a clinically effective dose and communication between individuals with neuropathy and their primary care provider over 12 months. Interviewers collecting outcome data were blinded to intervention assignment. RESULTS: Some 1252 participants completed the baseline measures [mean age (sd): 67 (11.7), 53% female, 57% white, 8% Asian, 13% black, 20% Hispanic]. In total, 1179 participants (93%) completed follow-up (619 control, 560 intervention). Quality of life scores (intervention: 0.658 ± 0.094; control: 0.653 ± 0.092) and symptom severity were similar at baseline. The intervention had no effect on primary [EQ-5D: -0.002 (95% CI -0.01, 0.01), P = 0.623; pain: 0.295 (-0.75, 1.34), P = 0.579; sleep disruption: 0.342 (-0.18, 0.86), P = 0.196; lower extremity functioning: -0.079 (-1.27, 1.11), P = 0.896; depression: -0.462 (-1.24, 0.32); P = 0.247] or process outcomes. CONCLUSIONS: Automated telephone monitoring and feedback alone were not effective at improving quality of life or symptoms for people with symptomatic diabetic peripheral neuropathy. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02056431).

Differential Morphological and Biochemical Recovery from Chemotherapy-Induced Peripheral Neuropathy Following Paclitaxel, Ixabepilone, or Eribulin Treatment in Mouse Sciatic Nerves.

The reversibility of chemotherapy-induced peripheral neuropathy (CIPN), a disabling and potentially permanent side effect of microtubule-targeting agents (MTAs), is becoming an increasingly important issue as treatment outcomes improve. The molecular mechanisms regulating the variability in time to onset, severity, and time to recovery from CIPN between the common MTAs paclitaxel and eribulin are unknown. Previously (Benbow et al. in Neurotox Res 29:299-313, 2016), we found that after 2 weeks of a maximum tolerated dose (MTD) in mice, paclitaxel treatment resulted in severe reductions in axon area density, higher frequency of myelin abnormalities, and increased numbers of Schwann cell nuclei in sciatic nerves. Biochemically, eribulin induced greater microtubule-stabilizing effects than paclitaxel. Here, we extended these comparative MTD studies to assess the recovery from these short-term effects of paclitaxel, eribulin, and a third MTA, ixabepilone, over the course of 6 months. Paclitaxel induced a persistent reduction in axon area density over the entire 6-month recovery period, unlike ixabepilone- or eribulin-treated animals. The abundance of myelin abnormalities rapidly declined after cessation of all drugs but recovered most slowly after paclitaxel treatment. Paclitaxel- and ixabepilone- but not eribulin-treated animals exhibited increased Schwann cell numbers during the recovery period. Tubulin composition and biochemistry rapidly returned from MTD-induced levels of α-tubulin, acetylated α-tubulin, and end-binding protein 1 to control levels following cessation of drug treatment. Taken together, sciatic nerve axons recovered more rapidly from morphological effects in eribulin- and ixabepilone-treated animals than in paclitaxel-treated animals and drug-induced increases in protein expression levels following paclitaxel and eribulin treatment were relatively transient.

Graphitization of Glassy Carbon after Compression at Room Temperature.

Glassy carbon is a technologically important material with isotropic properties that is nongraphitizing up to ∼3000 °C and displays complete or "superelastic" recovery from large compression. The pressure limit of these properties is not yet known. Here we use experiments and modeling to show permanent densification, and preferred orientation occurs in glassy carbon loaded to 45 GPa and above, where 45 GPa represents the limit to the superelastic and nongraphitizing properties of the material. The changes are explained by a transformation from its sp^{2} rich starting structure to a sp^{3} rich phase that reverts to fully sp^{2} bonded oriented graphite during pressure release.

Proteomics Profiling of Pancreatic Cancer and Pancreatitis for Biomarkers Discovery.

Pancreatic cancer is one of the most aggressive malignancies with an increase in incidence predicted, particularly in African Americans. Pancreatic cancer is considered a silent disease with poor prognosis and a lack of early biomarkers for detection. Proteomics has been applied in many diseases for identifying or discovering biomarkers. It has long been suggested that chronic pancreatitis may be a risk factor for developing pancreatic cancer. This study identified proteins that are altered in expression in pancreatic cancer and pancreatitis compared to normal using proteomic technology. Proteins were extracted from laser captured micro-dissected tissues and separated in 2-DPAGE and imaged. The protein profiles of pancreatic cancer and pancreatitis are similar but differed with the protein profile of normal adjacent tissues. Representative proteins, overexpressed in tumor and pancreatitis but not normal tissues, were excised from gels, subjected to in-gel digestion, and analyzed by MALDI-TOF mass spectrometry. Proteins identified included transferrin, ER-60 protein, proapolipoprotein, tropomyosin 1, alpha 1 actin precursor, ACTB protein, and gamma 2 propeptide, aldehyde dehydrogenase 1A1, pancreatic lipase and annexin A1. Several proteins, which were shown in pancreatic cancer, were also observed in pancreatitis samples. Understanding the role of these specific proteins and their mechanistic action will give insights into their involvement in pancreatic cancers.

A method for maintaining vascular access when Impella exchange is required.

A 45-year old male with no prior cardiac history, presented with cardiogenic shock in the setting of an anterolateral ST elevation myocardial infarction. We first placed a 2.5 Impella for hemodynamic support, and proceeded with emergent percutaneous coronary intervention to the proximal LAD. Several hours following percutaneous coronary intervention (PCI), the patient became acutely hypotensive and an echocardiogram revealed the Impella catheter was kinked within the left ventricle. The patient was taken back to the cath lab for Impella adjustment; however, damage to the distal catheter required the Impella be exchanged. As the patient was therapeutically anticoagulated and on dual antiplatelet therapy, we modified the Impella catheter in order to maintain existing vascular access during Impella exchange. This case demonstrates our method for maintaining vascular access during Impella exchange, thereby eliminating the need for a second arterial puncture. © 2017 Wiley Periodicals, Inc.

European and Mediterranean hydroclimate responses to tropical volcanic forcing over the last millennium.

Volcanic eruptions have global climate impacts, but their effect on the hydrologic cycle is poorly understood. We use a modified version of superposed epoch analysis, an eruption year list collated from multiple datasets, and seasonal paleoclimate reconstructions (soil moisture, precipitation, geopotential heights, and temperature) to investigate volcanic forcing of spring and summer hydroclimate over Europe and the Mediterranean over the last millennium. In the western Mediterranean, wet conditions occur in the eruption year and the following 3 years. Conversely, northwestern Europe and the British Isles experience dry conditions in response to volcanic eruptions, with the largest moisture deficits in post-eruption years 2 and 3. The precipitation response occurs primarily in late spring and early summer (April-July), a pattern that strongly resembles the negative phase of the East Atlantic Pattern. Modulated by this mode of climate variability, eruptions force significant, widespread, and heterogeneous hydroclimate responses across Europe and the Mediterranean.

Individuals with a vestibular-related disorder use a somatosensory-dominant strategy for postural orientation after inclined stance.

OBJECTIVES: The visual, somatosensory, and vestibular systems are critical for establishing a sensorimotor set for postural control and orientation. The goal of this study was to assess how individuals with a vestibular-related disorder keep their balance following prolonged stance on an inclined surface. We hypothesize that subjects will show greater reliance on the somatosensory system than age-matched controls as inferred by the presence of a forward postural lean aftereffect following the inclined stance (i.e., a positive response). RESULTS: The results revealed an underlying somatosensory-dominant strategy for postural control in the vestibular group: 100% of the subjects tested positive compared to 58% in the control group (P=.006). CONCLUSION: Individuals with a vestibular-related disorder use a somatosensory-dominant strategy for postural orientation following prolonged inclined stance. The implications for the management of this population are discussed.

Mental health, migration stressors and suicidal ideation among Latino immigrants in Spain and the United States.

BACKGROUND: Immigration stress appears to augment the risk for suicide behaviors for Latinos. Yet, specific risk factors that contribute to suicidal ideation (SI) among diverse Latino immigrant populations are not well established. METHODS: Data were collected in Boston, Madrid and Barcelona using a screening battery assessing mental health, substance abuse risk, trauma exposure, demographics, and sociocultural factors. Prevalence rates of lifetime and 30-day SI were compared across sites. Logistic regression modeling was used to identify sociodemographic, clinical, and sociocultural-contextual factors associated with 30-day SI. RESULTS: Five hundred and sixty-seven Latino patients from primary care, behavioral health and HIV clinics and community agencies participated. Rates of lifetime SI ranged from 29-35%; rates for 30-day SI were 21-23%. Rates of SI were not statistically different between sites. Factors associated with SI included exposure to discrimination, lower ethnic identity, elevated family conflict, and low sense of belonging (P<0.01). In the adjusted model, higher scores on depression, posttraumatic stress disorder, and trauma exposure were significantly associated with 30-day SI (OR=1.14, 1.04, and 7.76, respectively). Greater number of years living in the host country was significantly associated with increased odds of having SI (OR=2.22) while having citizenship status was associated with lower odds (OR=0.45). CONCLUSION: Latinos suffering depression, trauma exposure, and immigration stressors are more likely to experience SI. Despite differences in country of origin, education, and other demographic factors between countries, rates of SI did not differ. Recommendations for prevention and clinical practice for addressing suicidal ideation risk among Latino immigrants are discussed.

Systems genetic and pharmacological analysis identifies candidate genes underlying mechanosensation in the von Frey test.

Mechanical sensitivity is commonly affected in chronic pain and other neurological disorders. To discover mechanisms of individual differences in punctate mechanosensation, we performed quantitative trait locus (QTL) mapping of the response to von Frey monofilament stimulation in BXD recombinant inbred (BXD) mice. Significant loci were detected on mouse chromosome (Chr) 5 and 15, indicating the location of underlying polymorphisms that cause heritable variation in von Frey response. Convergent evidence from public gene expression data implicates candidate genes within the loci: von Frey thresholds were strongly correlated with baseline expression of Cacna2d1, Ift27 and Csnk1e in multiple brain regions of BXD strains. Systemic gabapentin and PF-670462, which target the protein products of Cacna2d1 and Csnk1e, respectively, significantly increased von Frey thresholds in a genotype-dependent manner in progenitors and BXD strains. Real-time polymerase chain reaction confirmed differential expression of Cacna2d1 and Csnk1e in multiple brain regions in progenitors and showed differential expression of Cacna2d1 and Csnk1e in the dorsal root ganglia of the progenitors and BXD strains grouped by QTL genotype. Thus, linkage mapping, transcript covariance and pharmacological testing suggest that genetic variation affecting Cacna2d1 and Csnk1e may contribute to individual differences in von Frey filament response. This study implicates Cacna2d1 and Ift27 in basal mechanosensation in line with their previously suspected role in mechanical hypersensitivity. Csnk1e is implicated for von Frey response for the first time. Further investigation is warranted to identify the specific polymorphisms involved and assess the relevance of these findings to clinical conditions of disturbed mechanosensation.

Internal ocean-atmosphere variability drives megadroughts in Western North America.

Multidecadal droughts that occurred during the Medieval Climate Anomaly represent an important target for validating the ability of climate models to adequately characterize drought risk over the near-term future. A prominent hypothesis is that these megadroughts were driven by a centuries-long radiatively forced shift in the mean state of the tropical Pacific Ocean. Here we use a novel combination of spatiotemporal tree-ring reconstructions of Northern Hemisphere hydroclimate to infer the atmosphere-ocean dynamics that coincide with megadroughts over the American West, and find that these features are consistently associated with ten-to-thirty year periods of frequent cold El Niño Southern Oscillation conditions and not a centuries-long shift in the mean of the tropical Pacific Ocean. These results suggest an important role for internal variability in driving past megadroughts. State-of-the art climate models from the Coupled Model Intercomparison Project phase 5, however, do not simulate a consistent association between megadroughts and internal variability of the tropical Pacific Ocean, with implications for our confidence in megadrought risk projections.

Integrating intensive care unit (ICU) surveillance into an ICU clinical care electronic system.

The intensive care unit (ICU) is the specialty with the highest prevalence of healthcare-associated infection (HCAI) in European hospitals and therefore a priority for surveillance of HCAI. Whereas surveillance is an essential part of an effective infection prevention and control (IPC) programme, all too often it consumes too much clinician and IPC team time, limiting the time available for quality improvement. The case for electronic surveillance is made in the literature from several countries on this basis. These studies indicate that electronic surveillance can improve validity, reduce time spent on surveillance, and provide opportunities for improvement in clinical decision-making and IPC action arising from surveillance. The Scottish ICU HAI surveillance system was established as part of an integrated audit and clinical care system. Investment in this technology infrastructure reduced the burden of data collection and has resulted in a focus on driving improvement in all Scottish ICUs. The experience in Scotland indicates that several critical components are necessary to optimize ICU HCAI surveillance, including: nationally agreed definitions and methods; national investment in information technology infrastructure to make it easier to follow clinical care pathways; leadership of surveillance by intensivists; piloting and validation to ensure confidence in the system; and strategic integration of national and local programmes. These elements have helped improve surveillance data locally, nationally, and at a European level, allowing clinical attention to be focused on the data rather than on the process of data collection.