Prediction and prevention of psychosis: current progress and future tasks

Prevention of psychoses has been intensively investigated within the past two decades, and particularly, prediction has been much advanced. Depending on the applied risk indicators, current criteria are associated with average, yet significantly heterogeneous transition rates of ≥30 % within 3 years, further increasing with longer follow-up periods. Risk stratification offers a promising approach to advance current prediction as it can help to reduce heterogeneity of transition rates and to identify subgroups with specific needs and response patterns, enabling a targeted intervention. It may also be suitable to improve risk enrichment. Current results suggest the future implementation of multi-step risk algorithms combining sensitive risk detection by cognitive basic symptoms (COGDIS) and ultra-high-risk (UHR) criteria with additional individual risk estimation by a prognostic index that relies on further predictors such as additional clinical indicators, functional impairment, neurocognitive deficits, and EEG and structural MRI abnormalities, but also considers resilience factors. Simply combining COGDIS and UHR criteria in a second step of risk stratification produced already a 4-year hazard rate of 0.66. With regard to prevention, two recent meta-analyses demonstrated that preventive measures enable a reduction in 12-month transition rates by 54-56 % with most favorable numbers needed to treat of 9-10. Unfortunately, psychosocial functioning, another important target of preventive efforts, did not improve. However, these results are based on a relatively small number of trials; and more methodologically sound studies and a stronger consideration of individual profiles of clinical needs by modular intervention programs are required

Hypoxic treatment of human dual placental perfusion induces a preeclampsia-like inflammatory response.

Preeclampsia is a human pregnancy-specific disorder characterized by a placental pro-inflammatory response in combination with an imbalance of angiogenic factors and clinical symptoms, including hypertension and proteinuria. Insufficient uteroplacental oxygenation in preeclampsia due to impaired trophoblast invasion during placentation is believed to be responsible for many of the molecular events leading to the clinical manifestations of this disease. We investigated the use of hypoxic treatment of the dual placental perfusion system as a model for preeclampsia. A modified perfusion technique allowed us to achieve a mean soluble oxygen tension within the intervillous space (IVS) of 5-7% for normoxia and <3% for hypoxia (as a model for preeclampsia). We assayed for the levels of different inflammatory cytokines, oxidative stress markers, as well as other factors, such as endothelin (ET)-1 that are known to be implicated as part of the inflammatory response in preeclampsia. Our results show a significant increase under hypoxia in the levels of different inflammatory cytokines, including IL-6 (P=0.002), IL-8 (P<0.0001), TNF-α (P=0.032) and IFN-γ (P=0.009) at 360 min in maternal venous samples (n=6). There was also a significant increase in ET-1 levels under hypoxia both on the maternal side at 30 min (P=0.003) and fetal side at 360 min (P=0.036) (n=6). Other markers of oxidative stress, including malondialdehyde and 8-iso-protaglandin F2α (P=0.009) also show increased levels. Overall, these findings indicate that exposure of ex vivo dually perfused placental tissue to hypoxia provides a useful model for mimicking the inflammatory response characteristic of preeclampsia. This would therefore provide a powerful tool for studying and further delineating the molecular mechanisms involved in the underlying pathophysiology of preeclampsia.

Infection rate of emergency bolt-kit vs. non-emergency conventional implanted silver bearing external ventricular drainage catheters.

BACKGROUND Bolt-kit systems are increasingly used as an alternative to conventional external cerebrospinal fluid (CSF) drainage systems. Since 2009 we regularly utilize bolt-kit external ventricular drainage (EVD) systems with silver-bearing catheters inserted manually with a hand drill and skull screws for emergency ventriculostomy. For non-emergency situations, we use conventional ventriculostomy with subcutaneous tunneled silver-bearing catheters, performed in the operating room with a pneumatic drill. This retrospective analysis compared the two techniques in terms of infection rates. METHODS 152 patients (aged 17-85 years, mean=55.4 years) were included in the final analysis; 95 received bolt-kit silver-bearing catheters and 57 received conventionally implanted silver-bearing catheters. The primary endpoint combined infection parameters: occurrence of positive CSF culture, colonization of catheter tips, or elevated CSF white blood cell counts (>4/μl). Secondary outcome parameters were presence of microorganisms in CSF or on catheter tips. Incidence of increased CSF cell counts and number of patients with catheter malposition were also compared. RESULTS The primary outcome, defined as analysis of combined infection parameters (occurrence of either positive CSF culture, colonization of the catheter tips or raised CSF white blood cell counts >4/μl)was not significantly different between the groups (58.9% bolt-kit group vs. 63.2% conventionally implanted group, p=0.61, chi-square-test). The bolt-kit group was non-inferior and not superior to the conventional group (relative risk reduction of 6.7%; 90% confidence interval: -19.9% to 25.6%). Secondary outcomes showed no statistically significant difference in the incidence of microorganisms in CSF (2.1% bolt-kit vs. 5.3% conventionally implanted; p=0.30; chi-square-test). CONCLUSIONS This analysis indicates that silver-bearing EVD catheters implanted with a bolt-kit system outside the operating room do not significantly elevate the risk of CSF infection as compared to conventional implant methods.

Comparison of (31)P saturation and inversion magnetization transfer in human liver and skeletal muscle using a clinical MR system and surface coils.

(31)P MRS magnetization transfer ((31)P-MT) experiments allow the estimation of exchange rates of biochemical reactions, such as the creatine kinase equilibrium and adenosine triphosphate (ATP) synthesis. Although various (31)P-MT methods have been successfully used on isolated organs or animals, their application on humans in clinical scanners poses specific challenges. This study compared two major (31)P-MT methods on a clinical MR system using heteronuclear surface coils. Although saturation transfer (ST) is the most commonly used (31)P-MT method, sequences such as inversion transfer (IT) with short pulses might be better suited for the specific hardware and software limitations of a clinical scanner. In addition, small NMR-undetectable metabolite pools can transfer MT to NMR-visible pools during long saturation pulses, which is prevented with short pulses. (31)P-MT sequences were adapted for limited pulse length, for heteronuclear transmit-receive surface coils with inhomogeneous B1 , for the need for volume selection and for the inherently low signal-to-noise ratio (SNR) on a clinical 3-T MR system. The ST and IT sequences were applied to skeletal muscle and liver in 10 healthy volunteers. Monte-Carlo simulations were used to evaluate the behavior of the IT measurements with increasing imperfections. In skeletal muscle of the thigh, ATP synthesis resulted in forward reaction constants (k) of 0.074 ± 0.022 s(-1) (ST) and 0.137 ± 0.042 s(-1) (IT), whereas the creatine kinase reaction yielded 0.459 ± 0.089 s(-1) (IT). In the liver, ATP synthesis resulted in k = 0.267 ± 0.106 s(-1) (ST), whereas the IT experiment yielded no consistent results. ST results were close to literature values; however, the IT results were either much larger than the corresponding ST values and/or were widely scattered. To summarize, ST and IT experiments can both be implemented on a clinical body scanner with heteronuclear transmit-receive surface coils; however, ST results are much more robust against experimental imperfections than the current implementation of IT.

Parallel adaptations to nectarivory in parrots, key innovations and the diversification of the Loriinae

Specialization to nectarivory is associated with radiations within different bird groups, including parrots. One of them, the Australasian lories, were shown to be unexpectedly species rich. Their shift to nectarivory may have created an ecological opportunity promoting species proliferation. Several morphological specializations of the feeding tract to nectarivory have been described for parrots. However, they have never been assessed in a quantitative framework considering phylogenetic nonindependence. Using a phylogenetic comparative approach with broad taxon sampling and 15 continuous characters of the digestive tract, we demonstrate that nectarivorous parrots differ in several traits from the remaining parrots. These trait-changes indicate phenotype–environment correlations and parallel evolution, and may reflect adaptations to feed effectively on nectar. Moreover, the diet shift was associated with significant trait shifts at the base of the radiation of the lories, as shown by an alternative statistical approach. Their diet shift might be considered as an evolutionary key innovation which promoted significant non-adaptive lineage diversification through allopatric partitioning of the same new niche. The lack of increased rates of cladogenesis in other nectarivorous parrots indicates that evolutionary innovations need not be associated one-to-one with diversification events.

Efficiency of frost-cracking processes through space and time: An example from the eastern Italian Alps

It is widely accepted that climate has a strong impact and exerts important feedbacks on erosional processes and sediment transport mechanisms. However, the extent at which climate influences erosion is still a matter of debate. In this paper we test whether frost-cracking processes and related temperature variations can influence the sediment production and surface erosion in a small catchment situated in the eastern Italian Alps. To this extent, we first present a geomorphic map of the region that we complement with published 10Be-based denudation rates. We then apply a preexisting heat-flow model in order to analyze the variations of the frost-cracking intensity (FCI) in the study area, which could have controlled the sediment production in the basin. Finally, we compare the model results with the pattern of denudation rates and Quaternary deposits in the geomorphic map. The model results, combined with field observations, mapping, and quantitative geomorphic analyses, reveal that frost-cracking processes have had a primary role in the production of sediment where the intensity of sediment supply has been dictated and limited by the combined effect of temperature variations and conditions of bedrock preservation. These results highlight the importance of a yet poorly understood process for the production of sediment in mountain areas.

Towards a spatial understanding of trade-offs in sustainable development: A meso-scale analysis of the nexus between land use, poverty, and environment in the Lao PDR

In land systems, equitably managing trade-offs between planetary boundaries and human development needs represents a grand challenge in sustainability oriented initiatives. Informing such initiatives requires knowledge about the nexus between land use, poverty, and environment. This paper presents results from Lao PDR, where we combined nationwide spatial data on land use types and the environmental state of landscapes with village-level poverty indicators. Our analysis reveals two general but contrasting trends. First, landscapes with paddy or permanent agriculture allow a greater number of people to live in less poverty but come at the price of a decrease in natural vegetation cover. Second, people practising extensive swidden agriculture and living in intact environments are often better off than people in degraded paddy or permanent agriculture. As poverty rates within different landscape types vary more than between landscape types, we cannot stipulate a land use–poverty–environment nexus. However, the distinct spatial patterns or configurations of these rates point to other important factors at play. Drawing on ethnicity as a proximate factor for endogenous development potentials and accessibility as a proximate factor for external influences, we further explore these linkages. Ethnicity is strongly related to poverty in all land use types almost independently of accessibility, implying that social distance outweighs geographic or physical distance. In turn, accessibility, almost a precondition for poverty alleviation, is mainly beneficial to ethnic majority groups and people living in paddy or permanent agriculture. These groups are able to translate improved accessibility into poverty alleviation. Our results show that the concurrence of external influences with local—highly contextual—development potentials is key to shaping outcomes of the land use–poverty–environment nexus. By addressing such leverage points, these findings help guide more effective development interventions. At the same time, they point to the need in land change science to better integrate the understanding of place-based land indicators with process-based drivers of land use change.

Osteotomy of the greater trochanter: effect on gluteus medius function

PURPOSE Advancement of the greater trochanter alters the function of the gluteus medius muscle. However, with the exception of clinical studies and biomechanical lever arm studies, no publications that analyze the consequences of advancement of the greater trochanter on the muscle function exist. The aim of the study was to analyze the mechanical changes of gluteus medius after osteotomy of the greater trochanter in a lab setting. METHODS An anatomical study of origin and insertion of the gluteus medius was carried out on four hips. Based on the dissections, a string model was developed dividing the muscle into five sectors. Changes in muscle fiber length were measured for every 10° of flexion, internal and external rotation and abduction with the trochanter in anatomic, proximalized and distalized positions. RESULTS Distalization of the trochanter leads to an imbalance of muscle action, moving the isometric sector of the muscle anteriorly with more muscle sectors being active during flexion and less during extension. Stretching of the muscle increases passive forces but decreases the force generation capacity of the muscle and at the same time increased muscle fiber excursion may require more energy consumption, which may explain earlier fatigue of the abductor musculature after distalization of the trochanter. For abduction, distalization of the muscle attachment leads to a change in contraction pattern from isometric to isotonic. Optimal balancing and excursion of the muscle is when the tip of the greater trochanter is at level with the hip rotation center. CONCLUSIONS In hips with high riding trochanter, the optimal position is at the level of the center of hip rotation. Excessive distalization should be avoided. As the conclusions and considerations are based on a lab setting, transfer to clinical practice may not necessarily apply.

Are there signs of change in gendered language use in children's early reading material?

In this study we investigate the relative frequencies of female and male terms in early reading material for children using the Children’s Printed Word Database as a resource. As roles of females and males have changed over time it is of interest to see if there has been a corresponding change in representations of females and males in children’s books. We carried out analyses regarding different words related to gender. Except for nouns referring to relatives, we found in all word groups a preponderance of male terms. The imbalance of male and female pronouns is equivalent to that reported by Carroll, Davies, and Richman (1971) in a frequency count of printed words in children’s book in the USA conducted some 40 years ago. The results are discussed in terms of gender inequality in reading materials and the development of social mores and stereotypical ideas.

Prevalence and determinants of type 2 diabetes among Filipino Americans in Houston metropolitan statistical area, Texas

Diabetes in adults (type 2) has emerged as a world health problem. Prevalence and risk factors have been found to vary in different populations. The wide range of prevalence rates worldwide indicates the importance of genetic and environmental factors in the etiology of the disease. The few available studies suggest that Filipinos are among the higher-risk groups for developing diabetes. This cross-sectional study estimated the overall prevalence rate of type 2 diabetes among Filipino Americans, ages 20–74 years and residents of Houston Metropolitan Statistical Area, Texas, to be 16.1%. The observed high prevalence was associated with age, sex, family history of diabetes, obesity, region of birth; and, in women, gestational diabetes and income. The diabetic Filipino Americans had a higher proportion of parental history of diabetes, medical history of hypertension, and history of smoking; were physically less active, but generally non-obese, compared with the United States diabetic population. ^

The Economic Case for Fiscal Federalism in Scotland

In this paper we consider the case for assigning tax revenues to Scotland, by which we mean that taxes levied on Scottish tax bases should be returned to the Scottish budget. The budget, however, would continue to be supplemented by transfers from the Westminster budget. This arrangement differs from the current situation whereby public spending is largely financed by a bloc grant from Westminster. Our suggestion falls short of full fiscal federalism for Scotland . meaning that Scotland had control over choice of tax base and of tax rates, and fiscal transfers from Westminster would be minimal. We use propositions drawn from the theory of fiscal federalism to argue for a smaller vertical imbalance between taxes retained in Scotland and public spending in Scotland. A closer matching of spending with taxes would better signal to beneficiaries the true costs of public spending in terms of taxes raised. It would also create more complete incentives for politicians to provide public goods and services in quantities and at qualities that voters are actually willing to pay for. Under the current bloc grant system, the marginal tax cost of spending does not enter into political agents. calculations as spending is out of a fixed total budget. Moreover, the Scottish electorate is hindered in signaling its desire for local public goods and services since the size of the total budget is determined by a rigid formula set by Westminster. At the present time we reject proposals for full fiscal federalism because in sharply reducing vertical imbalance in the Scottish budget, it is likely to worsen horizontal balance between Scotland and the other UK regions. Horizontal balance occurs where similarly situated regions enjoy the same per capita level of public goods and services at the same per capita tax cost. The complete removal of the bloc grant under full fiscal federalism would remove the mechanism that currently promotes horizontal equity in the UK. Variability in own-source tax revenues creates other problems with full fiscal federalism. Taxes derived from North Sea oil would constitute a large proportion of Scottish taxes, but these are known to be volatile in the face of variable oil prices and the pound-dollar exchange rate. At the present time variability in oil tax revenue is absorbed by Westminster. Scotland is insulated through the bloc grant. This risk sharing mechanism would be lost with full fiscal federalism. It is true that Scotland could turn to financial markets to tide itself over oil tax revenue downturns, but as a much smaller and less diversified financial entity than the UK as a whole it would probably have to borrow on less favorable terms than can Westminster. Scotland would have to bear this extra cost itself. Also, with full fiscal federalism it is difficult to see how the Scottish budget could be used as a macroeconomic stabilizer. At present, tax revenue downturns in Scotland - together with the steady bloc grant - are absorbed through an increase in vertical imbalance. This acts as an automatic stabilizer for the Scottish economy. No such mechanism would exist under full fiscal federalism. The borrowing alternative would still exist but on the less favorable terms - as with borrowing to finance oil tax shortfalls.

Performance evaluation in Bayesian adaptive randomization

Bayesian adaptive randomization (BAR) is an attractive approach to allocate more patients to the putatively superior arm based on the interim data while maintains good statistical properties attributed to randomization. Under this approach, patients are adaptively assigned to a treatment group based on the probability that the treatment is better. The basic randomization scheme can be modified by introducing a tuning parameter, replacing the posterior estimated response probability, setting a boundary to randomization probabilities. Under randomization settings comprised of the above modifications, operating characteristics, including type I error, power, sample size, imbalance of sample size, interim success rate, and overall success rate, were evaluated through simulation. All randomization settings have low and comparable type I errors. Increasing tuning parameter decreases power, but increases imbalance of sample size and interim success rate. Compared with settings using the posterior probability, settings using the estimated response rates have higher power and overall success rate, but less imbalance of sample size and lower interim success rate. Bounded settings have higher power but less imbalance of sample size than unbounded settings. All settings have better performance in the Bayesian design than in the frequentist design. This simulation study provided practical guidance on the choice of how to implement the adaptive design. ^

Factors contributing to the attrition of women in the African-American Nutrition for Life study

Background. There is currently a push to increase the number of minorities in cancer clinical trials in an effort to reduce cancer health disparities. Overcoming barriers to clinical trial research for minorities is necessary if we are to achieve the goals of Healthy People 2010. To understand the unexpectedly high rate of attrition in the A NULIFE study, the research team examined the perceived barriers to participation among minority women. The purpose of this study was to determine if either personal or study-related factors influenced healthy pre-menopausal women aged 25-45 years to terminate their participation in the A NULIFE Study. We hypothesized that personal factors were the driving forces for attrition rates in the prevention trial.^ Methods. The target population consisted of eligible women who consented to the A NULIFE study but withdrew prior to being randomized (N= 46), as well as eligible women who completed the informed consent process for the A NULIFE study and withdrew after randomization (N= 42). Examination of attrition rates in this study occurred at a time point when 10 out of 12 participant groups had completed the A NULIFE study. Data involving the 2 groups that were actively engaged in study activities were not used in this analysis. A survey instrument was designed to query the personal and study-related factors that were believed to have contributed to the decision to terminate participation in the A NULIFE study.^ Results. Overall, the highest ranked personal reason that influenced withdrawal from the study was being “too busy” with other obligations. The second highest ranked factor for withdrawal was work obligations. Whereas, more than half of all participants agreed that they were well-informed about the study and considered the study personnel to be approachable, 54% of participants would have been inclined to remain in the study if it were located at a local community center.^ Conclusions. Time commitment was likely a major factor for withdrawal from the A NULIFE study. Future investigators should implement trials within participant communities where possible. Also, focus group settings may provide detailed insight into factors that contribute to the attrition of minorities in cancer clinical trials.^

Assessment of cancer incidence in Titus County, Texas, 1977--1984

The purpose of this study was to determine the incidence of cancer in Titus County, Texas, through the identification of all cases of cancer that occurred in residents of the county during the period from 1977 to 1984. Data gathered from Texas Cancer Registry, hospital records, and death certificates were analyzed with regard to anatomic site, race, sex, age, city of residence, and place of birth. Adjustment of incidence rates by sex and race allowed comparisons with U.S. rates provided by the Surveillance, Epidemiology, and End Results Program (SEER).^ Seven hundred sixty-six (766) cancer cases were identified for the eight year period during 171,536 person-years of observation. In whites, statistically significant standardized incidence ratios (SIR) were found for leukemia (males SIR = 2.70 and females SIR = 2.26), melanoma (males SIR = 1.90 and females SIR = 2.25), lung (males SIR = 1.45) and for multiple myeloma (both sexes combined SIR = 1.86). In blacks, significant excess numbers of cases were found for Hodgkin's disease (males SIR = 8.33 and females SIR = 13.3) and for esophagus and bone considering both sexes together (SIR = 2.68 and 12.54, respectively). Rates for blacks were based on a small population and therefore unstable. A statistically significant excess number of cases for all sites combined was found in Mount Pleasant residents (age-adjusted incidence rate = 563.6 per 100,000 per year).^ A review of possible environmental risk factors in the area: hazardous waste disposal site, lignite deposits, and petrochemical and poultry industries are presented. A need for further epidemiological and environmental studies to identify etiological factors that could be responsible for the excess number of leukemia cases are recommended. For melanoma, a public health educational program to teach the population methods of protection from sun exposure is also suggested. ^

AN INVESTIGATION OF THE RELIABILITY AND VALIDITY OF THE CENTER FOR EPIDEMIOLOGIC STUDIES DEPRESSION SCALE IN THREE ETHNIC GROUPS

Epidemiologic studies of mental disorder have called attention to the need for identifying untreated cases and to the inadequacies of the instruments available for this purpose. Accurate case ascertainment devices are the basis of sound epidemiology. Without these, neither case classification nor analytic studies of risk factors is possible.^ The purpose of this research was to examine the reliability and validity of an instrument designed to measure depressive symptoms in community populations--the Center for Epidemiologic Studies Depression Scale (CES-D Scale). Two particular foci of the study were whether or not the scale had the same statistical structure across three ethnic groups and whether or not the magnitude and pattern of rates of symptoms for these groups were affected by one source of response error, that due to response tendencies. The effects of age and education on the pattern and magnitude of rates also were examined. In addition, the reliability and validity of the measures of response tendencies were assessed.^ The study population consisted of residents of Alameda County, California. A stratified sample of approximately 700 whites, blacks and Mexican-Americans was interviewed in the summer and fall of 1978.^ The results of the analysis indicated that the scale was reliable and measured a similar content domain across the three ethnic groups. The unadjusted sex- and ethnic-specific rates of depressive symptoms showed an ethnic pattern for both sexes: rates for whites were lowest, those for Mexican-Americans were highest, and those for blacks were intermediate. Measures of response tendencies--need for social approval, trait desirability, and acquiescence--affected the magnitude of the rates for most comparisons. Likewise, the pattern of rates changed somewhat from that originally observed. The one fairly consistent observation was that rates for Mexican-American women were higher than those for the other two female subgroups in most of the comparisons. These results must be considered in the context of the reliability and validity assessment of the measures of response tendencies which indicated the tenuousness of these measures.^ Age affected the ethnic pattern of rates for men in an inconsistent way; for women, Mexican-Americans continued to have higher rates than whites or blacks in all age categories. Education affected the magnitude of rates for women but not for men. For both men and women, Mexican-Americans had higher rates in all educational strata. Rates for women showed an inverse association with education while those for men did not. ^