Leukoaraiosis Significantly Worsens Driving Performance of Ordinary Older Drivers

Background

Leukoaraiosis is defined as extracellular space caused mainly by atherosclerotic or demyelinated changes in the brain tissue and is commonly found in the brains of healthy older people. A significant association between leukoaraiosis and traffic crashes was reported in our previous study; however, the reason for this is still unclear.

Method

This paper presents a comprehensive evaluation of driving performance in ordinary older drivers with leukoaraiosis. First, the degree of leukoaraiosis was examined in 33 participants, who underwent an actual-vehicle driving examination on a standard driving course, and a driver skill rating was also collected while the driver carried out a paced auditory serial addition test, which is a calculating task given verbally. At the same time, a steering entropy method was used to estimate steering operation performance.

Results

The experimental results indicated that a normal older driver with leukoaraiosis was readily affected by external disturbances and made more operation errors and steered less smoothly than one without leukoaraiosis during driving; at the same time, their steering skill significantly deteriorated.

Conclusions

Leukoaraiosis worsens the driving performance of older drivers because of their increased vulnerability to distraction.     

Stress amplifies sex differences in primate prefrontal profiles of gene expression

Background

Stress is a recognized risk factor for mood and anxiety disorders that occur more often in women than men. Prefrontal brain regions mediate stress coping, cognitive control, and emotion. Here, we investigate sex differences and stress effects on prefrontal cortical profiles of gene expression in squirrel monkey adults.

Methods

Dorsolateral, ventrolateral, and ventromedial prefrontal cortical regions from 18 females and 12 males were collected after stress or no-stress treatment conditions. Gene expression profiles were acquired using HumanHT-12v4.0 Expression BeadChip arrays adapted for squirrel monkeys.

Results

Extensive variation between prefrontal cortical regions was discerned in the expression of numerous autosomal and sex chromosome genes. Robust sex differences were also identified across prefrontal cortical regions in the expression of mostly autosomal genes. Genes with increased expression in females compared to males were overrepresented in mitogen-activated protein kinase and neurotrophin signaling pathways. Many fewer genes with increased expression in males compared to females were discerned, and no molecular pathways were identified. Effect sizes for sex differences were greater in stress compared to no-stress conditions for ventromedial and ventrolateral prefrontal cortical regions but not dorsolateral prefrontal cortex.

Conclusions

Stress amplifies sex differences in gene expression profiles for prefrontal cortical regions involved in stress coping and emotion regulation. Results suggest molecular targets for new treatments of stress disorders in human mental health.

     

An embedded longitudinal multi-faceted qualitative evaluation of a complex cluster randomized controlled trial aiming to reduce clinically important errors in medicines management in general practice

Background

Children who witness interparental violence are at a heightened risk for developing psychosocial, behavioral and cognitive problems, as well as posttraumatic stress symptoms. For these children the psycho-educational secondary prevention program 'En nu ik...!' ('It's my turn now!') has been developed. This program includes specific therapeutic factors focused on emotion awareness and expression, increasing feelings of emotional security, teaching specific coping strategies, developing a trauma narrative, improving parent-child interaction and psycho-education. The main study aim is to evaluate the effectiveness of the specific therapeutic factors in the program. A secondary objective is to study mediating and moderating factors.

Methods/design

This study is a prospective multicenter randomized controlled trial across cities in the Netherlands. Participants (N = 140) are referred to the secondary preventive intervention program by police, social work, women shelters and youth (mental health) care. Children, aged 6-12 years, and their parents, who experienced interparental violence are randomly assigned to either the intervention program or the control program. The control program is comparable on nonspecific factors by offering positive attention, positive expectations, recreation, distraction, warmth and empathy of the therapist, and social support among group participants, in ways that are similar to the intervention program. Primary outcome measures are posttraumatic stress symptoms and emotional and behavioral problems of the child. Mediators tested are the ability to differentiate and express emotions, emotional security, coping strategies, feelings of guilt and parent-child interaction. Mental health of the parent, parenting stress, disturbances in parent-child attachment, duration and severity of the domestic violence and demographics are examined for their moderating effect. Data are collected one week before the program starts (T1), and one week (T2) and six months (T3) after finishing the program. Both intention-to-treat and completer analyses will be done.

Discussion

Adverse outcomes after witnessing interparental violence are highly diverse and may be explained by multiple risk factors. An important question for prevention programs is therefore to what extent a specific focus on potential psychotrauma is useful. This trial may point to several directions for optimizing public health response to children's exposure to interparental violence.

Trial registration

Netherlands Trial Register (NTR): NTR3064     

Omgaan met somberheid op oudere leeftijd: een kwalitatieve studie

Background

To gain new insights for support for older people with low mood, we explored the perceptions of ‘screenpositive’ older people on underlying causes and possible solutions.

Design and method

We conducted two in-depth interviews with 38 participants (≥77 years) who screened positive for depressive symptoms in general practice. To investigate the influence of the presence of complex health problems, we included 19 persons with and 19 without complex problems. Complex problems were defined as a combination of functional, somatic, psychological or social problems.

Results

All participants used several cognitive, social or practical coping strategies. Four patterns emerged: mastery, acceptance, ambivalence, and need for support. Some participants, especially those with complex problems, were ambivalent about possible interventions.

Conclusion

Most older participants perceived their coping strategies as sufficient. General practitioners can support self-management by exploring the (effectiveness of) personal coping strategies, providing information, elaborating on perceptions of risks and discussing alternative options with older persons.

     

A genetic association analysis of cognitive ability and cognitive ageing using 325 markers for 109 genes associated with oxidative stress or cognition

Background

Non-pathological cognitive ageing is a distressing condition affecting an increasing number of people in our 'ageing society'. Oxidative stress is hypothesised to have a major role in cellular ageing, including brain ageing.

Results

Associations between cognitive ageing and 325 single nucleotide polymorphisms (SNPs), located in 109 genes implicated in oxidative stress and/or cognition, were examined in a unique cohort of relatively healthy older people, on whom we have cognitive ability scores at ages 11 and 79 years (LBC1921). SNPs showing a significant positive association were then genotyped in a second cohort for whom we have cognitive ability scores at the ages of 11 and 64 years (ABC1936). An intronic SNP in the APP gene (rs2830102) was significantly associated with cognitive ageing in both LBC1921 and a combined LBC1921/ABC1936 analysis (p < 0.01), but not in ABC1936 alone.

Conclusion

This study suggests a possible role for APP in normal cognitive ageing, in addition to its role in Alzheimer's disease.     

Attention Deficit Hyperactivity Disorder Symptoms,Sleepiness and Accidental Risk in 36140 Regularly Registered Highway Drivers

Background

Attention Deficit Hyperactivity Disorder (ADHD) is a frequent neurodevelopmental disorder that increases accidental risk. Recent studies show that some patients with ADHD can also suffer from excessive daytime sleepiness but there are no data assessing the role of sleepiness in road safety in patients with ADHD. We conducted an epidemiological study to explore sleep complaints, inattention and driving risks among automobile drivers.

Methods and Findings

From August to September 2014, 491186 regular highway users were invited to participate in an Internet survey on driving habits. 36140 drivers answered a questionnaire exploring driving risks, sleep complaints, sleepiness at the wheel, ADHD symptoms (Adult ADHD Self-Report Scale) and distraction at the wheel. 1.7% of all drivers reported inattention-related driving accidents and 0.3% sleep-related driving accidents in the previous year. 1543 drivers (4.3%) reported ADHD symptoms and were more likely to report accidents than drivers without ADHD symptoms (adjusted OR = 1.24, [1.03–1.51], p < .021). 14.2% of drivers with ADHD symptoms reported severe excessive daytime sleepiness (Epworth Sleepiness Scale >15) versus 3.2% of drivers without ADHD symptoms and 20.5% reported severe sleepiness at the wheel versus 7.3%. Drivers with ADHD symptoms reported significantly more sleep-related (adjusted OR = 1.4, [1.21–1.60], p < .0001) and inattention-related (adjusted OR = 1.9, [1.71–2.14], p<0001) near misses than drivers without ADHD symptoms. The fraction of near-misses attributable to severe sleepiness at the wheel was 4.24% for drivers without ADHD symptoms versus 10,35% for drivers with ADHD symptoms.

Conclusion

Our study shows that drivers with ADHD symptoms have more accidents and a higher level of sleepiness at the wheel than drivers without ADHD symptoms. Drivers with ADHD symptoms report more sleep-related and inattention-related near misses, thus confirming the clinical importance of exploring both attentional deficits and sleepiness at the wheel in these drivers. Road safety campaigns should be improved to better inform drivers of these accidental risks.     

Review and classification of variability analysis techniques with clinical applications

Background

Representation of independent biophysical sources using Fourier analysis can be inefficient because the basis is sinusoidal and general. When complex fractionated atrial electrograms (CFAE) are acquired during atrial fibrillation (AF), the electrogram morphology depends on the mix of distinct nonsinusoidal generators. Identification of these generators using efficient methods of representation and comparison would be useful for targeting catheter ablation sites to prevent arrhythmia reinduction.

Method

A data-driven basis and transform is described which utilizes the ensemble average of signal segments to identify and distinguish CFAE morphologic components and frequencies. Calculation of the dominant frequency (DF) of actual CFAE, and identification of simulated independent generator frequencies and morphologies embedded in CFAE, is done using a total of 216 recordings from 10 paroxysmal and 10 persistent AF patients. The transform is tested versus Fourier analysis to detect spectral components in the presence of phase noise and interference. Correspondence is shown between ensemble basis vectors of highest power and corresponding synthetic drivers embedded in CFAE.

Results

The ensemble basis is orthogonal, and efficient for representation of CFAE components as compared with Fourier analysis (p ≤ 0.002). When three synthetic drivers with additive phase noise and interference were decomposed, the top three peaks in the ensemble power spectrum corresponded to the driver frequencies more closely as compared with top Fourier power spectrum peaks (p ≤ 0.005). The synthesized drivers with phase noise and interference were extractable from their corresponding ensemble basis with a mean error of less than 10%.

Conclusions

The new transform is able to efficiently identify CFAE features using DF calculation and by discerning morphologic differences. Unlike the Fourier transform method, it does not distort CFAE signals prior to analysis, and is relatively robust to jitter in periodic events. Thus the ensemble method can provide a useful alternative for quantitative characterization of CFAE during clinical study.     

Common Traffic Violations of Bus Drivers in Urban China: An Observational Study

Objective

To report common traffic violations in bus drivers and the factors that influence those violations in urban China.

Methods

We conducted an observational study to record three types of traffic violations among bus drivers in Changsha City, China: illegal stopping at bus stations, violating traffic light signals, and distracted driving. The behaviors of bus drivers on 32 routes (20% of bus routes in the city) were observed. A two-level Poisson regression examined factors that predicted bus driver violations.

Results

The incidence of illegal stopping at bus stations was 20.2%. Illegal stopping was less frequent on weekends, sunny days, and at stations with cameras, with adjusted incidence rate ratios (IRRs) of 0.81, 0.65 and 0.89, respectively. The incidence of violating traffic light signals was 2.2%, and was lower on cloudy than sunny days (adjusted IRR: 0.60). The incidence of distracted driving was 3.3%. The incidence of distracted driving was less common on cloudy days, rainy or snowy days, and foggy/windy/dusty days compared to sunny days, with adjusted IRRs of 0.54, 0.55 and 0.07, respectively.

Conclusion

Traffic violations are common in bus drivers in urban China and they are associated with the date, weather, and presence of traffic cameras at bus station. Further studies are recommended to understand the behavioral mechanisms that may explain bus driver violations and to develop feasible prevention measures.     

Soil drainage and phosphorus depletion contribute to retrogressive succession along a New Zealand chronosequence

Background and aims

Models of retrogressive succession have emphasised the role of phosphorus (P) depletion in driving biomass loss on surfaces of increasing geologic age, but the influence of impeded drainage on old surfaces has received much less attention. We tested whether poor drainage contributed to changes in ecosystem properties along a 291,000-year chronosequence in New Zealand (the Waitutu chronosequence).

Methods

Soil and ecosystem properties were measured at 24 evenly distributed points within each of eight 1.5 ha plots located on young, intermediate and old surfaces. Regression analyses tested whether drainage, in addition to P, affected ecosystem functioning. A complementary fertilization experiment tested whether P was indeed limiting on the most nutrient-depleted sites.

Results

Most phosphorus depletion occurred in the early stages of pedogenesis (within 24,000 years), and the older surfaces were similar in soil-P contents, whereas drainage was initially good but became increasingly impeded with surface age. In the fertilizer experiment, species showed positive responses to both nitrogen (N) and P addition on the oldest surfaces, supporting Walker and Syer’s model. However, water table depth was also found to be strongly correlated with plant species composition, forest basal area, light transmission, and litter decomposition when comparisons were made across sites, emphasising that it too has strong influences on ecosystem processes.

Conclusions

Poor drainage influences the process of retrogressive succession along the Waitutu chronosequence. We discuss the implications of our work with regard to other chronosequences, suggesting that topography is likely to have strong influences on retrogressive processes.     

Normalization references for Europe and North America for application with USEtox? characterization factors

Purpose

In life cycle impact assessment, normalization can be a very effective tool for the life cycle assessment practitioner to interpret results and put them into perspective. The paper presents normalization references for the recently developed USEtox? model, which aims at calculating globally applicable characterization factors. Normalization references for Europe and North America are determined, and guidance for expansions to other geographical regions is provided.

Materials and methods

The base years of the European and North American inventories are 2004 and 2002/2008, respectively. Emission data were extracted from two literature sources referring to each of the considered regions. The inventory for North America was adapted to avoid extrapolation of data from other regions and thus bring consistency with the emission inventory for Europe. In spite of different inventory assumptions, a similar coverage of substances was obtained for both regions with relatively high representation of metals and a number of organic compounds, mainly consisting of non-methane volatile organic compounds and pesticides. The two inventory sets were eventually characterized with the characterization factors (CFs) calculated with the version 1.0 of the USEtox? model and substance database; both interim and recommended CFs were used.

Results and discussion

Normalization references are provided for Europe and North America for the three USEtox? toxic impact categories; ratios between the normalization references for the two regions in all cases lie below a factor of 3. Causes for the observed discrepancies are found to be different inventory assumptions as well as variations in the type and intensity of actual emissions between the two regions. Additional causes are inventories that only cover a limited number of substances, and the characterization model, which can only provide interim factors for certain substances like metal compounds. Based on these causes and on a review of recent studies on normalization references, a list of substances to be prioritized when collecting emission data was built, demonstrating the importance of metals.

Conclusions

In the perspective of further refining the presented normalization references and of calculating new references for other regions, guidance is provided including a list of priority substances that should be considered when building emission inventories for normalization references.     

Quantifying anthropogenic mobilization,flows (in product systems) and emissions of fixed nitrogen in process-based environmental life cycle assessment: rationale,methods and application to a life cycle inventory

Purpose

Anthropogenic perturbation of the nitrogen cycle is attracting increasing attention as both an environmental and societal concern. Here, we provide the rationale and propose methods for independent treatment of anthropogenic mobilization, flows (in product systems) and emissions of fixed nitrogen in process-based environmental life cycle assessment.

Methods

We propose a simple methodology for aggregating N flows in life cycle assessment (LCA), with supporting characterization factors for all nitrogen-containing compounds on the Organization for Economic Cooperation and Development High Production Volume Chemical List for which specific chemical formulae are available, as well as all nitrogen-containing flows in the International Reference Life Cycle Data System. We subsequently apply our method and characterization factors to a life cycle inventory data set representing a subset of the consumption attributable to an average EU-27 consumer and compare the results against previously published estimates for nitrogen emissions at the consumer level that were generated using alternative methods/approaches.

Results and discussion

We derive a suite of over 2,000 characterization factors for nitrogen-containing compounds. Overall, the results generated by applying our method and characterization factors to the European Commission Basket-of-Products life cycle inventory data set are consistent with those observed from studies having a similar scope but different methodological approach.

Conclusions

This outcome suggests that anthropogenic mobilization, flows (in product systems) and emissions of fixed nitrogen can, indeed, be systematically inventoried and aggregated in process-based LCA for the purpose of better understanding and managing anthropogenic impacts on the global nitrogen cycle using the methods and characterization factors we propose.     

A cradle-to-gate life cycle assessment of wood fibre-reinforced polylactic acid (PLA) and polylactic acid/thermoplastic starch (PLA/TPS) biocomposites

Purpose

Biopolymers are considered to be environmentally friendlier than petroleum-based polymers, but little is known about their environmental performance against petroleum-based products. This paper presents the results of a life cycle assessment (LCA) of two prototype biocomposite formulations produced by extrusion of wood fibre with either polylactic acid (PLA) or a blend of PLA and locally produced thermoplastic starch (TPS).

Methods

The study followed the LCA methodology outlined in the two standards set out by the International Organization for Standardization (ISO): ISO 14040 and ISO 14044 of 2006. A life cycle inventory (LCI) for the biocomposite formulations was developed, and a contribution analysis was performed to identify the significant inputs. Environmental performances of the two formulations were then compared with each other and polypropylene (PP), a petroleum-based polymer. The US Environmental Protection Agency’s impact assessment method, “TRACI: The Tool for the Reduction and Assessment of Chemical and Other Environmental Impacts”, was combined with Cumulative Energy Demand (a European method) in order to characterize the inventory flows. Environmental impact categories chosen for the analysis were the following: global warming, stratospheric ozone depletion, acidification of land and water, eutrophication, smog, human health (respiratory, carcinogenic, and non-carcinogenic) effects and ecotoxicity.

Results and discussion

We found that PLA is the significant input which contributes mostly to fossil fuel consumption, acidification and respiratory and smog effects. Impacts from PLA transport from the faraway source significantly added more burden to its contributions. TPS causes less environmental burden compared to PLA; the environmental performance of the biocomposite improved when a blend of PLA and TPS is used in formulating the biocomposite. The two formulations performed better than PP in all the environmental impact categories except eutrophication effects, which is important on a regional basis.

Conclusions

The following conclusions were drawn from this study:

• PLA is the environmentally significant input among the three raw materials.
• TPS causes less environmental burden than PLA. Environmental performance of the biocomposite improves in the life cycle energy consumption, fossil energy use, ozone depletion and non-carcinogenic impact categories when a blend of PLA and TPS is used.
• The biocomposite can outperform PP in all the impact categories except eutrophication effects if manufactured using hydroelectricity.

The biopolymer could be a potential alternative to PP as it could cause less of a burden to the environment on a cradle-to-gate basis. Environmental impacts at the complete life cycle levels should be looked into in order to fully understand its potential.     

Shoot growth, root growth and resource capture under limiting water and N supply for two cultivars of lettuce (Lactuca sativa L.)

Background and aims

To improve vegetable crops adapted to low input and variable resource availability, better understanding is needed of root system functioning, including nitrogen and water capture.

Methods

This study quantified shoot and root development and patterns of water and nitrate capture of two lettuce cultivars subjected to temporary drought at two development stages (Trial 1) or to continuous, localized drought and/or nitrate shortage (Trial 2).

Results

In Trial 1, early drought slowed down shoot and root growth, whereas late drought enhanced root proliferation in the top 0.1 m. Nitrate capture during drought was sustained by increased nitrate inflow from deeper layers. Plants did not recover fully from drought after re-watering. In Trial 2, root proliferation was stimulated in the drier soil compartment partially compensating reduced water availability and nitrate mobility. Under nitrate shortage, root proliferation was enhanced in the compartment where nitrate was more abundant, irrespective of water availability.

Conclusions

Changes observed in the root system are ‘feed-forward’ mechanisms to sustain resource capture in a limiting growing environment. The type of stress (drought or nitrate shortage) affects coping strategies; nitrate concentration in the soil solution, combined with the nutritional status of the plant will determine the stress response.     

Investigator experiences with financial conflicts of interest in clinical trials

Background

Sub-threshold depression is common, impairs functioning, and increases the risk of developing major depression. Although psychological treatments have been investigated for sub-threshold depression, they are costly. A less costly alternative could be an educational health promotion campaign about effective self-help for depression symptoms. The aim of the study is to test the efficacy of a low-cost email-based mental health promotion campaign in changing self-help behaviour and preventing more severe depression in adults with sub-threshold depression.

Methods/Design

The project is a randomised controlled trial of an automated preventive email-intervention aimed at people with sub-threshold depression. Adults aged 18+ with sub-threshold depression (as measured with the Patient Health Questionnaire-9), who are not already receiving professional treatment for depression, are eligible for admission to the study. Internet users will sign up via the study website http://www.moodmemos.com and be randomly allocated to receive emails twice weekly for six weeks containing either self-help coping advice or general information about depression as a control. Outcomes will be assessed at the start, midpoint, and end of the intervention, as well as six months later. Outcomes assessed include symptoms, incidence of major depression, psychological distress, social and occupational functioning, coping strategies, and coping self-efficacy. The primary hypothesis is that the Mood Memo emails containing coping strategies will reduce depression symptoms and be better at preventing major depression than the control emails that contain general information about depression.

Discussion

Promotion of actions an individual can take to prevent physical disease is a technique often used in public health. This study applies this approach to mental health, and explores whether a low-cost, easily disseminated email-based campaign can improve self-help coping behaviour and prevent depression in adults with sub-threshold depression.

Trial Registration

Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12609000925246     

On the “rigorous proof of fuzzy error propagation with matrix-based LCI”

Purpose

This short note re-examines the proof of fuzzy error propagation with matrix-based LCI in Heijungs and Tan (Int J Life Cycle Assess 15:1014–1019, 2010) paper (referred to as HT hereafter), published in this journal. We provide counter examples to the claims made therein, point out the key error in their proof and identify correct sufficient conditions under which the largest (smallest) values of the given α-cuts of fuzzy numbers in the technology matrix yield the smallest (largest) scaling factors.

Methods

HT uses iterative perturbations of a matrix to seemingly provide a rigorous proof of this result. Flaws in their arguments are identified and demonstrated by way of a counterexample. A classical result on monotonic property of the inverse of M-matrices leads to the correct sufficient conditions under which HT result holds.

Results

Since counter examples can be found, the result stated in HT is not, in general, guaranteed.

Conclusions

As claimed in the HT paper, checking the upper and lower bounds of α-cuts may not be sufficient to describe the uncertainty (the full range of values) in the final inventory. However, slightly stronger conditions on the fuzzy technology matrix provide these inventory bounds.     

Effects of gender,age, family support,and treatment on perceived stress and coping of patients with type 2 diabetes mellitus

Background

We previously found that the empowerment of patients with type 2 diabetes mellitus can be strongly affected by gender and age in addition to self-managed diet and exercise behaviors and treatment. This study was to examine the effects of gender, age, family support, and treatment on the perceived stress and coping of patients with type 2 diabetes mellitus living with family.

Methods

A survey was conducted of 140 adults with type 2 diabetes mellitus who were living with family. There was no significant difference in hemoglobin A1c (HbA1c) between male and female. Perceived stress and coping were measured with the Japanese version of the Appraisal of Diabetes Scale and the Lazarus Type Stress Coping Inventory. Stepwise regression analysis and path analysis were performed to identify factors that affect the perceived stress and coping of patients.

Results

(1) Perceived stress and coping were strongly affected by gender. (2) Perceived stress and coping were affected by age for males, but perceived stress was not affected by age for females. However, females showed a greater “psychological impact of diabetes” than did males. Females aged between 50 and 69 years engaged in active problem solving, but awareness of diabetes was low. (3) Treatment regimens had an effect on HbA1c for both sexes, and diet therapy affected the awareness of diabetes of males and coping of females. (4) For females, “sense of self-control” was strongly associated with coping, and those who were living with non-spouse family members had a greater psychological impact of diabetes than those living with only their spouse. (5) For males, coping was strongly affected by living with their spouse.

Conclusions

The results suggest that perceived stress, coping, and diet regimen are deeply associated with gender and age and that a male with type 2 diabetes mellitus living with his spouse is strongly dependent on support from the spouse. It is important to take into account gender, age, and family environment to provide patients with an individualized approach to addressing perceived stress and to provide education program for coping that can maximize treatment and maintain better, continuous glycemic control.

     

Accumulation of potential driver genes with genomic alterations predicts survival of high-risk neuroblastoma patients

Background

Neuroblastoma is the most common pediatric malignancy with heterogeneous clinical behaviors, ranging from spontaneous regression to aggressive progression. Many studies have identified aberrations related to the pathogenesis and prognosis, broadly classifying neuroblastoma patients into high- and low-risk groups, but predicting tumor progression and clinical management of high-risk patients remains a big challenge.

Results

We integrate gene-level expression, array-based comparative genomic hybridization and functional gene-interaction network of 145 neuroblastoma patients to detect potential driver genes. The drivers are summarized into a driver-gene score (DGscore) for each patient, and we then validate its clinical relevance in terms of association with patient survival. Focusing on a subset of 48 clinically defined high-risk patients, we identify 193 recurrent regions of copy number alterations (CNAs), resulting in 274 altered genes whose copy-number gain or loss have parallel impact on the gene expression. Using a network enrichment analysis, we detect four common driver genes, ERCC6, HECTD2, KIAA1279, EMX2, and 66 patient-specific driver genes. Patients with high DGscore, thus carrying more copy-number-altered genes with correspondingly up- or down-regulated expression and functional implications, have worse survival than those with low DGscore (P?=?0.006). Furthermore, Cox proportional-hazards regression analysis shows that, adjusted for age, tumor stage and MYCN amplification, DGscore is the only significant prognostic factor for high-risk neuroblastoma patients (P?=?0.008).

Conclusions

Integration of genomic copy number alteration, expression and functional interaction-network data reveals clinically relevant and prognostic putative driver genes in high-risk neuroblastoma patients. The identified putative drivers are potential drug targets for individualized therapy.

Reviewers

This article was reviewed by Armand Valsesia, Susmita Datta and Aleksandra Gruca.

     

Managing concerns about falls in older people: evaluation of the implementation of an evidence-based program

Introduction

A cognitive behavioral program reduced concerns about falling and related avoidance behavior among older community-dwelling adults in a randomized controlled trial. In the current study we examined the effects and acceptability of the program after nation-wide implementation into home care organizations in The Netherlands.

Methods

In a one-group pretest–posttest study with data collection before the start of the program and at 2 and 4 months, the effects and acceptability of the program were assessed in 125 community-dwelling older people. The outcomes of the effect evaluation included concerns about falls, related avoidance behavior, falls, fall-related medical attention, feelings of anxiety, symptoms of depression, and loneliness.

Results

Pretest-posttest analyses with the Wilcoxon signed-rank test and the paired t-test showed significant improvements at 4 months for concerns about falls, activity avoidance, number of falls in the past 2 months, feelings of anxiety, and symptoms of depression. No significant differences were shown for the other outcomes.

Discussion

After implementation in home care organizations, the outcomes indicate positive program effects on concerns about falls, avoidance behavior, and falls in community-dwelling older people. Given the similarity in results, i.e. between those of the previously performed randomized controlled trial and those of the current pretest-posttest study, we conclude that the program can be successfully implemented in practice. This article is an adjusted, Dutch version of Zijlstra GA, van Haastregt JC, Du Moulin MF, de Jonge MC, van der Poel A, Kempen GI. Effects of the implementation of an evidenc-based program to manage concerns about falls in older adults. The Gerontologist 2013;53(5):839–849; doi:10.1093/geront/gns142     

Irrigation mix: how to include water sources when assessing freshwater consumption impacts associated to crops

Purpose

Impacts of activities related to freshwater use are gaining interest among the life cycle assessment (LCA) community and several approaches are nowadays available in the literature. However, the general trend still is to ignore the assessment of its impact or, luckily, its inclusion on the inventory. This paper describes a procedure to incorporate water source information at the inventory level and evaluate the influence of that profile on the environmental impact assessment level.

Methods

The methodology lies on two main elements: the “irrigation mix” concept and the freshwater ecosystem impact indicator already defined in the literature. By doing so, the results obtained can be easily integrated in LCA studies of irrigated crops, or more complex studies with agricultural ingredients, where only information regarding the amount (but not the origin) of irrigation water is available.

Results and discussion

The results make more visible the benefits associated to the use of nonconventional, artificial water sources, by quantifying the improvement achieved on the water stress of a specific basin. Besides, the irrigation mix gives a better picture of the real contribution of irrigation to other impact categories (here, the global warming potential). Finally, the results were applied in a LCA study of lettuce production (an irrigated product cultivated in the studied region), and the method was analyzed against the criteria defined by the International Reference Life Cycle Data System handbook.

Conclusions

The inclusion of the water mix in the inventory level (irrigation profile) as well as in the impact assessment level (water stress index) is straightforward to apply by LCA practitioners, resulting in a more realistic assessment of the impacts of freshwater consumption associated to crops. The implementation on a case study allowed the quantification of promoting alternative water sources in a region suffering from significant water stress as well as to improve knowledge on the environmental impact associated to freshwater consumed by one of the irrigated crops grown there. We recommend using the approach defined here in order to check its applicability to other river basins and products.