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Intracranial pressure (ICP) can be measured by a monitor placed into one of the lateral ventricles; in the subarachnoid, subdural, or epidural spaces; or in the brain parenchyma.
ICP monitors should be placed in a patient’s nondominant hemisphere (e.g. right hemisphere in a right-handed person).
Kocher’s point is the external skin landmark most commonly used for insertion; at this point, the catheter trajectory to the frontal horn of the lateral ventricle avoids bridging veins, the superior sagittal sinus, and the motor strip. Kocher’s point is located 2 cm anterior to the coronal suture at the mid-pupillary line (2–3 cm lateral to midline). The coronal suture is approximately 11–12 cm from the base of the nose.
Alternative sites for placement include Keen’s point, which is located 2.5 cm posterior and superior to the top of the ear (posterior-parietal), a Frazier burr hole (occipital-parietal), and Dandy’s point (occipital).
Longitudinal studies of first episode of psychosis (FEP) patients are critical to understanding the dynamic clinical factors influencing functional outcomes; negative symptoms and verbal memory (VM) deficits are two such factors that remain a therapeutic challenge. This study uses white-gray matter contrast at the inner edge of the cortex, in addition to cortical thickness, to probe changes in microstructure and their relation with negative symptoms and possible intersections with verbal memory.
T1-weighted images and clinical data were collected longitudinally for patients (N = 88) over a two-year period. Cognitive data were also collected at baseline. Relationships between baseline VM (immediate/delayed recall) and rate of change in two negative symptom dimensions, amotivation and expressivity, were assessed at the behavioral level, as well as at the level of brain structure.
VM, particularly immediate recall, was significantly and positively associated with a steeper rate of expressivity symptom decline (r = 0.32, q = 0.012). Significant interaction effects between baseline delayed recall and change in expressivity were uncovered in somatomotor regions bilaterally for both white-gray matter contrast and cortical thickness. Furthermore, interaction effects between immediate recall and change in expressivity on cortical thickness rates were uncovered across higher-order regions of the language processing network.
This study shows common neural correlates of language-related brain areas underlying expressivity and VM in FEP, suggesting deficits in these domains may be more linked to speech production rather than general cognitive capacity. Together, white-gray matter contrast and cortical thickness may optimally inform clinical investigations aiming to capture peri-cortical microstructural changes.
By combining a focused inert-gas ion beam instrument and a custom magnetic-sector mass spectrometer, high spatial resolution imaging and chemical analysis are provided within a single instrument. Sub-nanometer image resolution is achieved by secondary electron (SE) imaging, limited only by the probe-size of the primary beam, while the spatial resolution for chemical mapping obtained via secondary ion mass spectrometry (SIMS) is limited mainly by beam-sample interactions to about 10 nm. This article introduces the background behind this development, describes the instrument and its various operating modes, and presents examples of its applications.
Environmental risk factors for dementia are poorly understood. Aluminium and fluorine in drinking water have been linked with dementia but uncertainties remain about this relationship.
In the largest longitudinal study in this context, we set out to explore the individual effect of aluminium and fluoride in drinking water on dementia risk and, as fluorine can increase absorption of aluminium, we also examine any synergistic influence on dementia.
We used Cox models to investigate the association between mean aluminium and fluoride levels in drinking water at their residential location (collected 2005–2012 by the Drinking Water Quality Regulator for Scotland) with dementia in members of the Scottish Mental Survey 1932 cohort who were alive in 2005.
A total of 1972 out of 6990 individuals developed dementia by the linkage date in 2012. Dementia risk was raised with increasing mean aluminium levels in women (hazard ratio per s.d. increase 1.09, 95% CI 1.03–1.15, P < 0.001) and men (1.12, 95% CI 1.03–1.21, P = 0.004). A dose-response pattern of association was observed between mean fluoride levels and dementia in women (1.34, 95% CI 1.28–1.41, P < 0.001) and men (1.30, 95% CI 1.22–1.39, P < 0.001), with dementia risk more than doubled in the highest quartile compared with the lowest. There was no statistical interaction between aluminium and fluoride levels in relation with dementia.
Higher levels of aluminium and fluoride were related to dementia risk in a population of men and women who consumed relatively low drinking-water levels of both.
Breakthrough Listen is a 10-yr initiative to search for signatures of technologies created by extraterrestrial civilisations at radio and optical wavelengths. Here, we detail the digital data recording system deployed for Breakthrough Listen observations at the 64-m aperture CSIRO Parkes Telescope in New South Wales, Australia. The recording system currently implements two modes: a dual-polarisation, 1.125-GHz bandwidth mode for single-beam observations, and a 26-input, 308-MHz bandwidth mode for the 21-cm multibeam receiver. The system is also designed to support a 3-GHz single-beam mode for the forthcoming Parkes ultra-wideband feed. In this paper, we present details of the system architecture, provide an overview of hardware and software, and present initial performance results.
We sought to assess the universal salt iodization (USI) strategy in Armenia by characterizing dietary iodine intake from naturally occurring iodine, salt-derived iodine in processed foods and salt-derived iodine in household-prepared foods.
Using a cross-sectional cluster survey model, we collected urine samples which were analysed for iodine and sodium concentrations (UIC and UNaC) and household salt samples which were analysed for iodine concentration (SI). SI and UNaC data were used as explanatory variables in multiple linear regression analyses with UIC as dependent variable, and the regression parameters were used to estimate the iodine intake sources attributable to native iodine and iodine from salt in processed foods and household salt.
Armenia is naturally iodine deficient; in 2004, the government mandated a USI strategy.
We recruited school-age children (SAC), pregnant women (PW) and non-pregnant women of reproductive age (WRA).
From thirteen sites covering all provinces, sufficient urine and table salt samples were obtained from 312 SAC, 311 PW and 332 WRA. Findings revealed significant differences between groups: contribution of native iodine ranged from 81% in PW to 46% in SAC, while household salt-derived iodine contributed from 19% in SAC to 1% in PW.
Differences between groups may reflect differences in diet. In all groups, household and processed food salt constituted a significant part of total iodine intake, highlighting the success and importance of USI in ensuring iodine sufficiency. There appears to be leeway to reduce salt intake without adversely affecting the iodine status of the population in Armenia.
There is increasing evidence for shared genetic susceptibility between schizophrenia and bipolar disorder. Although genetic variants only convey subtle increases in risk individually, their combination into a polygenic risk score constitutes a strong disease predictor.
To investigate whether schizophrenia and bipolar disorder polygenic risk scores can distinguish people with broadly defined psychosis and their unaffected relatives from controls.
Using the latest Psychiatric Genomics Consortium data, we calculated schizophrenia and bipolar disorder polygenic risk scores for 1168 people with psychosis, 552 unaffected relatives and 1472 controls.
Patients with broadly defined psychosis had dramatic increases in schizophrenia and bipolar polygenic risk scores, as did their relatives, albeit to a lesser degree. However, the accuracy of predictive models was modest.
Although polygenic risk scores are not ready for clinical use, it is hoped that as they are refined they could help towards risk reduction advice and early interventions for psychosis.
Declaration of interest
R.M.M. has received honoraria for lectures from Janssen, Lundbeck, Lilly, Otsuka and Sunovian.
To determine the effect of mandatory and nonmandatory influenza vaccination policies on vaccination rates and symptomatic absenteeism among healthcare personnel (HCP).
Retrospective observational cohort study.
This study took place at 3 university medical centers with mandatory influenza vaccination policies and 4 Veterans Affairs (VA) healthcare systems with nonmandatory influenza vaccination policies.
The study included 2,304 outpatient HCP at mandatory vaccination sites and 1,759 outpatient HCP at nonmandatory vaccination sites.
To determine the incidence and duration of absenteeism in outpatient settings, HCP participating in the Respiratory Protection Effectiveness Clinical Trial at both mandatory and nonmandatory vaccination sites over 3 viral respiratory illness (VRI) seasons (2012–2015) reported their influenza vaccination status and symptomatic days absent from work weekly throughout a 12-week period during the peak VRI season each year. The adjusted effects of vaccination and other modulating factors on absenteeism rates were estimated using multivariable regression models.
The proportion of participants who received influenza vaccination was lower each year at nonmandatory than at mandatory vaccination sites (odds ratio [OR], 0.09; 95% confidence interval [CI], 0.07–0.11). Among HCP who reported at least 1 sick day, vaccinated HCP had lower symptomatic days absent compared to unvaccinated HCP (OR for 2012–2013 and 2013–2014, 0.82; 95% CI, 0.72–0.93; OR for 2014–2015, 0.81; 95% CI, 0.69–0.95).
These data suggest that mandatory HCP influenza vaccination policies increase influenza vaccination rates and that HCP symptomatic absenteeism diminishes as rates of influenza vaccination increase. These findings should be considered in formulating HCP influenza vaccination policies.
New approaches are needed to safely reduce emergency admissions to hospital by targeting interventions effectively in primary care. A predictive risk stratification tool (PRISM) identifies each registered patient's risk of an emergency admission in the following year, allowing practitioners to identify and manage those at higher risk. We evaluated the introduction of PRISM in primary care in one area of the United Kingdom, assessing its impact on emergency admissions and other service use.
We conducted a randomized stepped wedge trial with cluster-defined control and intervention phases, and participant-level anonymized linked outcomes. PRISM was implemented in eleven primary care practice clusters (total thirty-two practices) over a year from March 2013. We analyzed routine linked data outcomes for 18 months.
We included outcomes for 230,099 registered patients, assigned to ranked risk groups.
Overall, the rate of emergency admissions was higher in the intervention phase than in the control phase: adjusted difference in number of emergency admissions per participant per year at risk, delta = .011 (95 percent Confidence Interval, CI .010, .013). Patients in the intervention phase spent more days in hospital per year: adjusted delta = .029 (95 percent CI .026, .031). Both effects were consistent across risk groups.
Primary care activity increased in the intervention phase overall delta = .011 (95 percent CI .007, .014), except for the two highest risk groups which showed a decrease in the number of days with recorded activity.
Introduction of a predictive risk model in primary care was associated with increased emergency episodes across the general practice population and at each risk level, in contrast to the intended purpose of the model. Future evaluation work could assess the impact of targeting of different services to patients across different levels of risk, rather than the current policy focus on those at highest risk.
Emergency admissions to hospital are a major financial burden on health services. In one area of the United Kingdom (UK), we evaluated a predictive risk stratification tool (PRISM) designed to support primary care practitioners to identify and manage patients at high risk of admission. We assessed the costs of implementing PRISM and its impact on health services costs. At the same time as the study, but independent of it, an incentive payment (‘QOF’) was introduced to encourage primary care practitioners to identify high risk patients and manage their care.
We conducted a randomized stepped wedge trial in thirty-two practices, with cluster-defined control and intervention phases, and participant-level anonymized linked outcomes. We analysed routine linked data on patient outcomes for 18 months (February 2013 – September 2014). We assigned standard unit costs in pound sterling to the resources utilized by each patient. Cost differences between the two study phases were used in conjunction with differences in the primary outcome (emergency admissions) to undertake a cost-effectiveness analysis.
We included outcomes for 230,099 registered patients. We estimated a PRISM implementation cost of GBP0.12 per patient per year.
Costs of emergency department attendances, outpatient visits, emergency and elective admissions to hospital, and general practice activity were higher per patient per year in the intervention phase than control phase (adjusted δ = GBP76, 95 percent Confidence Interval, CI GBP46, GBP106), an effect that was consistent and generally increased with risk level.
Despite low reported use of PRISM, it was associated with increased healthcare expenditure. This effect was unexpected and in the opposite direction to that intended. We cannot disentangle the effects of introducing the PRISM tool from those of imposing the QOF targets; however, since across the UK predictive risk stratification tools for emergency admissions have been introduced alongside incentives to focus on patients at risk, we believe that our findings are generalizable.
A predictive risk stratification tool (PRISM) to estimate a patient's risk of an emergency hospital admission in the following year was trialled in general practice in an area of the United Kingdom. PRISM's introduction coincided with a new incentive payment (‘QOF’) in the regional contract for family doctors to identify and manage the care of people at high risk of emergency hospital admission.
Alongside the trial, we carried out a complementary qualitative study of processes of change associated with PRISM's implementation. We aimed to describe how PRISM was understood, communicated, adopted, and used by practitioners, managers, local commissioners and policy makers. We gathered data through focus groups, interviews and questionnaires at three time points (baseline, mid-trial and end-trial). We analyzed data thematically, informed by Normalisation Process Theory (1).
All groups showed high awareness of PRISM, but raised concerns about whether it could identify patients not yet known, and about whether there were sufficient community-based services to respond to care needs identified. All practices reported using PRISM to fulfil their QOF targets, but after the QOF reporting period ended, only two practices continued to use it. Family doctors said PRISM changed their awareness of patients and focused them on targeting the highest-risk patients, though they were uncertain about the potential for positive impact on this group.
Though external factors supported its uptake in the short term, with a focus on the highest risk patients, PRISM did not become a sustained part of normal practice for primary care practitioners.
Optical matching of ASTER (Advanced Spaceborne Thermal Emission and Reflection Radiometer) satellite image pairs is used to determine the surface velocities of major glaciers across the central Karakoram. The ASTER images were acquired in 2006 and 2007, and cover a 60×120km region over Baltoro glacier, Pakistan, and areas to the north and west. The surface velocities were compared with differential global position system (GPS) data collected on Baltoro glacier in summer 2005. The ASTER measurements reveal fine details about ice dynamics in this region. For example, glaciers are found to be active over their termini even where they are very heavily debris-covered. The characteristics of several surge-type glaciers were measured, with terminus advances of several hundred meters per year and the displacement of trunk glaciers as surge glaciers pushed into them. This study is the first synthesis of glacier velocities across this region, and provides a baseline against which both past and future changes can be compared.
OBJECTIVES/SPECIFIC AIMS: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in the United States and increases risk for cirrhosis and liver cancer. Identifying modifiable risk factors for NAFLD could allow better targeting of prevention programs. Insulin resistance (IR) plays a significant role in the development and progression of NAFLD. IR is also an important precursor to the development of type 2 diabetes (T2DM). However, the development and duration of IR during young adulthood and its association with NAFLD and T2DM in midlife is unclear. To test whether trajectories of IR using homeostatic model assessment (HOMA-IR) change throughout early adulthood are associated with risk of prevalent NAFLD and T2DM among persons with NAFLD in midlife independent of current or baseline HOMA-IR. METHODS/STUDY POPULATION: Participants from the CARDIA study, a prospective multicenter population-based biracial cohort of adults (baseline age 18–30 years), underwent HOMA-IR measurement (≥8 h fasting and not pregnant) at baseline (1985–1986) and follow-up exam years 7, 10, 15, 20, and 25. At Year 25 (Y25, 2010–2011), liver fat was assessed by noncontrast computed tomography (CT). NAFLD was defined as CT liver attenuation <51 Hounsfield Units after exclusion of other causes of liver fat (alcohol/hepatitis/medications). Latent mixture modeling was used to identify 25-year trajectories in HOMA-IR over time. Multivariable logistic regression models were used to assess associations between HOMA-IR trajectory groups and prevalent NAFLD with adjustment for baseline or Y25 HOMA-IR. RESULTS/ANTICIPATED RESULTS: Among 3060 participants, we identified 3 distinct trajectory groups for HOMA-IR for individuals free from diabetes in middle adulthood: qualitatively low-stable (46.7% of the cohort), moderate-increasing (42.0%), and high-increasing (11.3%) with a NAFLD prevalence at Y25 of: 8.3%, 33.4%, and 63.5%, respectively (p-trend<0.0001). After adjustment for confounders (baseline smoking status, alcohol use, body mass index, physical activity score, systolic blood pressure, antihypertensive medication use, and total/HDL cholesterol ratio) and baseline HOMA-IR, increasing HOMA-IR trajectories were associated with greater NAFLD prevalence compared with the low-stable trajectory group [odds ratio (95% CI): 5.8 (4.3–7.9) and 22.3 (14.2–34.9) for moderate and high, respectively]. These associations were attenuated, but remained significant, even after controlling for current Y25 HOMA-IR [OR=3.6 (2.6–5.0) for moderate and 5.9 (3.4–10.3) for high (referent: low)]. Among participants with NAFLD (n=511), high-increasing HOMA-IR trajectory was associated with greater prevalent [OR=6.5 (1.6–25.7)] and incident [OR=8.7 (2.2–34.4)] T2DM at Y25 independent of confounders and Y25 HOMA-IR (referent: low-stable). DISCUSSION/SIGNIFICANCE OF IMPACT: In this community-based sample of individuals free from diabetes at baseline, an increasing HOMA-IR trajectory through young adulthood was associated with greater NAFLD prevalence in midlife. Knowledge of changes in IR throughout adulthood provides new information on the risk of T2DM among persons with NAFLD in midlife independent of current level of IR. These findings highlight early identification of increasing IR as a potential target for primary prevention of T2DM in the setting of NAFLD.
Chagas disease is caused by infection with the insect-transmitted protozoan Trypanosoma cruzi, and is the most important parasitic infection in Latin America. The current drugs, benznidazole and nifurtimox, are characterized by limited efficacy and toxic side-effects, and treatment failures are frequently observed. The urgent need for new therapeutic approaches is being met by a combined effort from the academic and commercial sectors, together with major input from not-for-profit drug development consortia. With the disappointing outcomes of recent clinical trials against chronic Chagas disease, it has become clear that an incomplete understanding of parasite biology and disease pathogenesis is impacting negatively on the development of more effective drugs. In addition, technical issues, including difficulties in establishing parasitological cure in both human patients and animal models, have greatly complicated the assessment of drug efficacy. Here, we outline the major questions that need to be addressed and discuss technical innovations that can be exploited to accelerate the drug development pipeline.
Depression and obesity are highly prevalent, and major impacts on public health frequently co-occur. Recently, we reported that having depression moderates the effect of the FTO gene, suggesting its implication in the association between depression and obesity.
To confirm these findings by investigating the FTO polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis.
The sample consists of 6902 individuals with depression and 6799 controls from three replication cohorts and two original discovery cohorts. Linear regression models were performed to test for association between rs9939609 and body mass index (BMI), and for the interaction between rs9939609 and depression status for an effect on BMI. Fixed and random effects meta-analyses were performed using METASOFT.
In the replication cohorts, we observed a significant interaction between FTO, BMI and depression with fixed effects meta-analysis (β=0.12, P = 2.7 × 10−4) and with the Han/Eskin random effects method (P = 1.4 × 10−7) but not with traditional random effects (β = 0.1, P = 0.35). When combined with the discovery cohorts, random effects meta-analysis also supports the interaction (β = 0.12, P = 0.027) being highly significant based on the Han/Eskin model (P = 6.9 × 10−8). On average, carriers of the risk allele who have depression have a 2.2% higher BMI for each risk allele, over and above the main effect of FTO.
This meta-analysis provides additional support for a significant interaction between FTO, depression and BMI, indicating that depression increases the effect of FTO on BMI. The findings provide a useful starting point in understanding the biological mechanism involved in the association between obesity and depression.
We have built and operated an ultra-wideband UHF pulsed-chirp radar for measuring firn stratigraphy from airborne platforms over the ice sheets of Greenland and West Antarctica. Our analysis found a wide range of capabilities, including imaging of post firn–ice transition horizons and sounding of shallow glaciers and ice shelves. Imaging of horizons to depths exceeding 600 m was possible in the colder interior regions of the ice sheet, where scattering from the ice surface and inclusions was minimal. The radar’s high sensitivity and large dynamic range point to loss tangent variations as the dominant mechanism for these englacial reflective horizons. The radar is capable of mapping interfaces with reflection coefficients as low as −80 dB near the firn–ice transition and as low as −64 dB at depths of 600 m. We found that firn horizon reflectivity strongly mirrored density variance, a result of the near-unity interfacial transmission coefficients. Zones with differing compaction mechanisms were also apparent in the data. We were able to sound many ice shelves and areas of shallow ice. We estimated ice attenuation rates for a few locations, and our attenuation estimates for the Ross Ice Shelf, West Antarctica, appear to agree well with earlier reported results.
A Description is given of the distribution and zonation of the dominant intertidal plants and animals found in a survey of rocky shores in Argyll, from Clachan Sound southwards to the south end of the Kintyre peninsula, thence northwards along the east side of Kintyre to Loch Fyne. Particular attention is given to two sheltered lochs, Loch Sween and West Loch Tarbert. Features of special interest in the area include: (i) a very small spring tide range (only 2–4 ft.) on much of the west coast of Kintyre, which results in a very compressed littoral zone by British standards; (ii) an unusual abundance of Chthamalus stellatus, often accompanied by a scarcity of Balanus balanoides, at very sheltered sites in Loch Sween and West Loch Tarbert (this problem is considered separately in Part II of the present paper); (iii) rich lower-shore populations in parts of the lochs, and especially associated with the Linne Mhuirich rapids in Loch Sween. In a concluding discussion the lower shore populations found in the survey area are compared with those observed in the rest of the British Isles. It is concluded that the rich lower-shore populations (often associated with rapid systems) that occur in many of the lochs on the west coast of Scotland constitute a major component of the littoral fauna and flora of the British Isles that has been largely unknown and neglected in the past because of the remoteness of many of the sites.