Predicting Cognitive Functioning for Patients with a High-Grade Glioma: Evaluating Different Representations of Tumor Location in a Common Space.

Cognitive functioning is increasingly considered when making treatment decisions for patients with a brain tumor in view of a personalized onco-functional balance. Ideally, one can predict cognitive functioning of individual patients to make treatment decisions considering this balance. To make accurate predictions, an informative representation of tumor location is pivotal, yet comparisons of representations are lacking. Therefore, this study compares brain atlases and principal component analysis (PCA) to represent voxel-wise tumor location. Pre-operative cognitive functioning was predicted for 246 patients with a high-grade glioma across eight cognitive tests while using different representations of voxel-wise tumor location as predictors. Voxel-wise tumor location was represented using 13 different frequently-used population average atlases, 13 randomly generated atlases, and 13 representations based on PCA. ElasticNet predictions were compared between representations and against a model solely using tumor volume. Preoperative cognitive functioning could only partly be predicted from tumor location. Performances of different representations were largely similar. Population average atlases did not result in better predictions compared to random atlases. PCA-based representation did not clearly outperform other representations, although summary metrics indicated that PCA-based representations performed somewhat better in our sample. Representations with more regions or components resulted in less accurate predictions. Population average atlases possibly cannot distinguish between functionally distinct areas when applied to patients with a glioma. This stresses the need to develop and validate methods for individual parcellations in the presence of lesions. Future studies may test if the observed small advantage of PCA-based representations generalizes to other data.

Executive functioning following surgery near the frontal aslant tract in low-grade glioma patients: A patient-specific tractography study.

BACKGROUND: The Frontal Aslant Tract (FAT) has been associated with executive functions (EF), but it remains unclear what role the FAT plays in EF, and whether preoperative dysfunction of the FAT is associated to long-lasting postsurgical executive impairments. METHODS: In this study, we examined the course of EF from pre-surgery (n = 75) to 3 (n = 61) and 12 (n = 25) months after surgery in patients with frontal and parietal low-grade gliomas (LGGs), to establish the degree to which long-term EF deficits exist. Secondly, we used patient-specific tractography to investigate the extent to which overlap of the tumor with the FAT, as well as integrity of the FAT, presurgery were related to EF on the short and longer term after surgery. RESULTS: LGG patients performed worse than healthy controls on all EF tests before and 3 months postsurgery. Whereas performances on three out of the four tests had normalized 1 year postsurgery (n = 26), performance on the cognitive flexibility test remained significantly worse than in healthy controls. Patients in whom the tumor overlapped with the core of the right FAT performed worse presurgery on three of the EF tests compared to those in whom the tumor did not overlap with the right FAT. Presurgical right FAT integrity was not related to presurgical EF, but only to postsurgical EF (from pre-to 3 months postsurgery). Longitudinal analyses demonstrated that patients with right (but not left) FAT core overlap performed on average worse over the pre- and postsurgical timepoints on the cognitive flexibility test. CONCLUSIONS: We emphasized that LGG patients perform worse than healthy controls on the EF tests, which normalizes 1-year postsurgery except for cognitive flexibility. Importantly, in patients with right hemispheric tumors, tumor involvement of the FAT was associated with worse pre- and 3- months postsurgical performance, specifically concerning cognitive flexibility.

German guideline for diagnosis and treatment of multiple sclerosis - a survey focusing neurologists in daily practise.

We performed a web-based survey among German-speaking neurologists to evaluate the acceptance of the 2021 German guideline in the diagnosis and treatment of multiple sclerosis. Based on 327 replies in total, the current survey largely reproduced the findings of an earlier, smaller survey on the prefinal consultation version of the guideline and confirmed high acceptance rates. Half of the participants were practising neurologists. Neurologists from MS centers with more than 500 patients per year (n=26) were more critical of the guideline. They reiterated some of the criticisms of the previous feedback, and, in particular, felt that safety aspects are overemphasized in the guideline, thereby superseding early aggressive therapy.

Implementation study of the 2021 German guideline for diagnosis and treatment of multiple sclerosis.

BACKGROUND: In May 2021, a new guideline on the diagnosis and treatment of multiple sclerosis and related disorders was released in Germany. Since the success of a guideline depends on how it integrates into everyday clinical practice, the German Society for Neurology (DGN) has launched a multimethod implementation project. Here we report on the results based on the consultation version of the guideline. METHODS: We used qualitative and quantitative data analyses to capture the nature and extent of barriers and facilitating factors to the implementation. We centered on the guideline's chapter A on diagnosis, relapse therapy, and immunotherapy of multiple sclerosis. We performed nine online focus group discussions and a web-based survey and analyzed emails and letters with comments from stakeholders and independent parties that were sent spontaneously or by invitation. RESULTS: 94 neurologists answered the survey, and ≥70% agreed with the recommendations of the guideline on each major content topic. Barriers to implementation were detected in group discussions and written input. The most controversial issues of the guideline were "early treatment", "criteria for starting or switching therapy", "stepwise escalation versus early aggressive treatment", "classification of drugs into three categories of efficacy" and the scenarios on "treatment cessation". Some appreciated the highly structured recommendations, but others felt that the guideline restricts the free choice of therapy, or they were afraid of recourse claims. Some considered the guideline as too cautious regarding treatment initiation, possibly delaying necessary therapies. Others appreciated that conflicts of interests of the guideline's authoring group were minimized and thought that the new guideline is clearer, more extensive and practical. CONCLUSION: In contrast to the survey, feedback in the focus group discussions and from individuals was diverse and sometimes more critical. Based on the overall feedback rate of about 250 people in relation to the number of 6500 board-certified neurologists in Germany, the overall appreciation of the guideline can only be considered as an indicator and not proof of acceptance. Results of this analysis were incorporated into several adjustments to the final guideline of 2021. Since the guideline is to be updated regularly under the auspices of a "living guideline", active interaction with users will continue to matter and help to improve it.

Group and Individual Change in Cognitive Functioning in Patients With 1 to 10 Brain Metastases Following Gamma Knife Radiosurgery.

AIMS: Stereotactic radiosurgery is increasingly used to treat multiple (four or more) brain metastases. Preserving cognitive functions is a highly relevant treatment goal because cognitive deteriorations may negatively affect a patient's quality of life. The aim of this study was to assess cognitive change, at the group and individual level, in patients with 1 to 10 brain metastases up to 9 months after Gamma Knife radiosurgery (GKRS). MATERIALS AND METHODS: Ninety-two patients with 1 to 10 newly diagnosed brain metastases, expected survival >3 months and Karnofsky Performance Status (KPS) ≥70 and 104 non-cancer controls were included. A neuropsychological test battery was administered before GKRS (n = 92) and at 3 (n = 66), 6 (n = 52) and 9 (n = 41) months after GKRS. The course of test performances, while taking into account practice effects, was analysed using linear mixed models. Pre-GKRS predictors of cognitive trajectories were analysed. To determine proportions of individuals with cognitive changes, reliable change indices, with correction for practice effects, were calculated. RESULTS: At the group level, immediate memory, working memory and information processing speed significantly improved over 9 months after GKRS. There were no cognitive declines. Neither number nor volume of brain metastases influenced cognitive change over time. At the individual level, proportions of patients with stable, improved or declined performances were comparable with controls, except for information processing speed (more individuals with improvements in patients) and motor dexterity (more improvements and declines in patients). CONCLUSIONS: Cognitive functioning in patients with 1 to 10 brain metastases was preserved, or improved, up to 9 months after GKRS. Neither number nor volume of brain metastases influenced cognitive performance.

Efficacy of antimicrobial interventions in reducing Salmonella enterica, Shiga toxin-producing Escherichia coli, Campylobacter, and Escherichia coli biotype I surrogates on non-chilled and chilled, skin-on and skinless pork.

Effect of various antimicrobial interventions on pork carcass cuts - skin-on and skinless, non-chilled and chilled - was studied. Carcass pieces were inoculated with Salmonella enterica, Shiga toxin-producing Escherichia coli (STEC), Escherichia coli pathogen surrogates or Campylobacter spp. Inoculated pieces were assigned to one of the following antimicrobial treatments: 2.5% and 5.0% room temperature lactic acid, 2.5% and 5.0% warm (55 °C) lactic acid, 400 ppm (0.4 mg/mL) room temperature peroxyacetic acid (PAA) or warm (55 °C) water. Treated pieces were sampled before antimicrobial treatment of non-chilled pork tissue, then at 30 m and 24 h post-treatment. For chilled pork, samples were collected after 24 h chilling and 30 m post-treatment. Lactic acid and PAA treatments reduced (P < 0.05) pathogenic and surrogate bacteria; warm water did not produce similar results. Objective and sensory color evaluations on treated pork indicated minimal negative impacts on pork color. Various antimicrobial interventions were effective in reducing surrogates on pork without diminishing quality.

Comparison of Salmonella Prevalence Rates in Bovine Lymph Nodes across Feeding Stages.

Peripheral lymph nodes (LNs) located in the fatty tissues of beef carcasses have been shown to harbor Salmonella and, thus, potentially contaminate ground beef. Salmonella prevalence within LNs is known to differ among feedlots. Two South Texas feeding operations (identified as locations A and B) known to harbor salmonellae in the feedlot environment, while historically producing cattle with opposing rates (one "high" and one "low") of Salmonella prevalence in LNs, were used in this study. To determine whether this difference was due to cattle source or factors associated with different stages of feeding, weanling steers of common and known origin were followed through normal feeding stages at both operations. Eighty Angus-sired beef steers were harvested at each of four feeding stages: 1, postweaning; 2, background or stocker; 3, 60 days on feed; and 4, 120 days on feed. Left and right subiliac and superficial cervical LNs ( n = 304) were collected from each carcass, and similar node types were pooled by animal ( n = 152). Results showed a difference ( P < 0.05) in prevalence of Salmonella in bovine lymph nodes between location A and location B and among feeding stages in location B. Salmonella was not isolated from any feeding stage 1 (postweaning) or location A LN samples. Within location B, there was an increase in Salmonella prevalence as cattle moved into later stages of feeding: at 22.2% (4 of 18), 77.8% (14 of 18), and 94.4% (17 of 18) for feeding stages 2, 3, and 4, respectively. Although the reasons for the differences seen between feeding operations and for increased Salmonella prevalence in LNs at later feeding stages remain unexplained, these results indicate that factors other than cattle source are likely influencing Salmonella prevalence in LNs.

National Beef Quality Audit-2016: Transportation, mobility, live cattle, and carcass assessments of targeted producer-related characteristics that affect value of market cows and bulls, their carcasses, and associated by-products.

The National Beef Quality Audit-2016 marks the fourth iteration in a series assessing the quality of live beef and dairy cows and bulls and their carcass counterparts. The objective was to determine the incidence of producer-related defects, and report cattle and carcass traits associated with producer management. Conducted from March through December of 2016, trailers (n = 154), live animals (n = 5,470), hide-on carcasses (n = 5,278), and hide-off hot carcasses (n = 5,510) were surveyed in 18 commercial packing facilities throughout the United States. Cattle were allowed 2.3 m2 of trailer space on average during transit indicating some haulers are adhering to industry handling guidelines for trailer space requirements. Of the mixed gender loads arriving at processing facilities, cows and bulls were not segregated on 64.4% of the trailers surveyed. When assessed for mobility, the greatest majority of cattle surveyed were sound. Since the inception of the quality audit series, beef cows have shown substantial improvements in muscle. Today over 90.0% of dairy cows are too light muscled. The mean body condition score for beef animals was 4.7 and for dairy cows and bulls was 2.6 and 3.3, respectively. Dairy cattle were lighter muscled, yet fatter than the dairy cattle surveyed in 2007. Of cattle surveyed, most did not have horns, nor any visible live animal defects. Unbranded hides were observed on 77.3% of cattle. Carcass bruising was seen on 64.1% of cow carcasses and 42.9% of bull carcasses. However, over half of all bruises were identified to only be minor in severity. Nearly all cattle (98.4%) were free of visible injection-site lesions. Current results suggest improvements have been made in cattle and meat quality in the cow and bull sector. Furthermore, the results provide guidance for continued educational and research efforts for improving market cow and bull beef quality.

Composition of free and peptide-bound amino acids in beef chuck, loin, and round cuts.

Meat is a food for humans. However, beef consumption in the United States has steadily declined by >14% over the past decade due to a variety of factors, including insufficient knowledge of animal protein. This study quantified all proteinogenic AA as well as nutritionally and physiologically significant nonproteinogenic AA and small peptides in beef cuts from 3 subprimals (chuck, round, and loin). Beef carcasses ( = 10) were selected at 3 commercial packing plants in the United States. Retail-cut samples were analyzed for the nitrogenous substances after acid, alkaline, or enzymatic hydrolysis and after deproteinization. In these chuck, round, and loin cuts, total amounts of glutamate (free plus peptide bound) were the highest (69-75 mg/g dry weight) followed by lysine, leucine, arginine, and glutamine in descending order. This is the first study to determine aspartate, asparagine, glutamate, and glutamine in meat proteins of any animal species. In all the beef samples evaluated, glutamine was the most abundant free AA (4.0-5.7 mg/g dry weight) followed by taurine, alanine, glutamate, and ß-alanine. Additionally, samples from all beef cuts had high concentrations of anserine, carnosine, and glutathione, which were 2.8 to 3.7, 15.2 to 24.2, and 0.68 to 0.79 mg/g dry weight, respectively. Beef top loin steaks appear to provide higher protein nutrition values than top round steaks and under blade roasts, but all are excellent sources of proteinogenic AA as well as antioxidant AA and peptides to improve human growth, development, and health. Our findings may help guide future decisions regarding human and animal nutrition.

Tenderness assessments of top loin steaks from retail markets in four U.S. cities.

The purpose of this study was to evaluate the tenderness of beef loin steaks from retail markets in 4 U.S. cities. Beef top loin steaks ( = 1,613) were obtained for Warner-Bratzler shear force (WBSF), slice shear force (SSF), and consumer sensory determinations. Personnel at 4 universities (California Polytechnic State University, Colorado State University, University of Missouri, and Texas A&M University) conducted the study over a 12-mo period. Enhanced/blade-tenderized top loin steaks had the lowest ( < 0.05) WBSF and SSF values, whereas nonenhanced top loin, bone-in steaks had the highest ( < 0.05) WBSF and SSF values. Enhanced/blade-tenderized top loin steaks received the highest ( < 0.05) ratings by consumers for palatability scores, whereas nonenhanced top loin, bone-in steaks had the lowest ( < 0.05) consumer panelist ratings. The USDA quality grade did have an effect ( < 0.05) on the tenderness of nonenhanced steaks but did not affect ( > 0.05) steaks that were enhanced/blade tenderized. The WBSF values and consumer sensory values for top loin steaks were comparable to the 2010 National Beef Tenderness Survey, signifying that no drastic changes in tenderness have occurred due to changes in antemortem or postmortem conditions.

Nutrient database improvement project: Separable components and proximate composition of raw and cooked retail cuts from the beef loin and round.

Beef nutrition research has become increasingly important domestically and internationally for the beef industry and its consumers. The objective of this study was to analyze the nutrient composition of ten beef loin and round cuts to update the nutrient data in the USDA National Nutrient Database for Standard Reference. Seventy-two carcasses representing a national composite of Yield Grade, Quality Grade, sex classification, and genetic type were identified from six regions across the U.S. Beef short loins, strip loins, tenderloins, inside rounds, and eye of rounds (NAMP # 173, 175, 190A, 169A, and 171C) were collected from the selected carcasses and shipped to three university meat laboratories for storage, retail fabrication, and raw/cooked analysis of nutrients. Sample homogenates from each animal were analyzed for proximate composition. These data provide updated information regarding the nutrient status of beef, in addition, to determining the influence of Quality Grade, Yield Grade, and sex classification on nutrient composition.

Frequency of and predictors for withholding patient safety concerns among oncology staff: a survey study.

Speaking up about patient safety is vital to avoid errors reaching the patient and to improve a culture of safety. This study investigated the prevalence of non-speaking up despite concerns for safety and aimed to identify predictors for withholding voice among healthcare professionals (HCPs) in oncology. A self-administered questionnaire assessed safety concerns, speaking up beliefs and behaviours among nurses and doctors from nine oncology departments. Multiple regression analysis was used to identify predictors for withholding safety concerns. A total of 1013 HCPs returned the completed survey (response rate 65%). Safety concerns were common among responders. Fifty-four per cent reported to recognise their colleagues making potentially harmful errors at least sometimes. A majority of responders reported at least some episodes of withholding concerns about patient safety. Thirty-seven per cent said they remained silent at least once when they had information that might have helped prevent an incident. Respondents believed that a high level of interpersonal, communication and coping skills are necessary to speak up about patient safety issues at their workplace. Higher levels of perceived advocacy for patient safety and psychological safety significantly decreased the frequency of withholding voice. Remaining silent about safety concerns is a common phenomenon in oncology. Improved strategies are needed to support staff in effective communication and make cancer care safer.

'Saying it without words': a qualitative study of oncology staff's experiences with speaking up about safety concerns.

OBJECTIVES: To explore the experiences of oncology staff with communicating safety concerns and to examine situational factors and motivations surrounding the decision whether and how to speak up using semistructured interviews. SETTING: 7 oncology departments of six hospitals in Switzerland. PARTICIPANTS: Diverse sample of 32 experienced oncology healthcare professionals. RESULTS: Nurses and doctors commonly experience situations which raise their concerns and require questioning, clarifying and correcting. Participants often used non-verbal communication to signal safety concerns. Speaking-up behaviour was strongly related to a clinical safety issue. Most episodes of 'silence' were connected to hygiene, isolation and invasive procedures. In contrast, there seemed to exist a strong culture to communicate questions, doubts and concerns relating to medication. Nearly all interviewees were concerned with 'how' to say it and in particular those of lower hierarchical status reflected on deliberate 'voicing tactics'. CONCLUSIONS: Our results indicate a widely accepted culture to discuss any concerns relating to medication safety while other issues are more difficult to voice. Clinicians devote considerable efforts to evaluate the situation and sensitively decide whether and how to speak up. Our results can serve as a starting point to develop a shared understanding of risks and appropriate communication of safety concerns among staff in oncology.

Diversity of ARSACS mutations in French-Canadians.

BACKGROUND: The growing number of spastic ataxia of Charlevoix-Saguenay (SACS) gene mutations reported worldwide has broadened the clinical phenotype of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). The identification of Quebec ARSACS cases without two known SACS mutation led to the development of a multi-modal genomic strategy to uncover mutations in this large gene and explore phenotype variability. METHODS: Search for SACS mutations by combining various methods on 20 cases with a classical French-Canadian ARSACS phenotype without two mutations and a group of 104 sporadic or recessive spastic ataxia cases of unknown cause. Western blot on lymphoblast protein from cases with different genotypes was probed to establish if they still expressed sacsin. RESULTS: A total of 12 mutations, including 7 novels, were uncovered in Quebec ARSACS cases. The screening of 104 spastic ataxia cases of unknown cause for 98 SACS mutations did not uncover carriers of two mutations. Compounds heterozygotes for one missense SACS mutation were found to minimally express sacsin. CONCLUSIONS: The large number of SACS mutations present even in Quebec suggests that the size of the gene alone may explain the great genotypic diversity. This study does not support an expanding ARSACS phenotype in the French-Canadian population. Most mutations lead to loss of function, though phenotypic variability in other populations may reflect partial loss of function with preservation of some sacsin expression. Our results also highlight the challenge of SACS mutation screening and the necessity to develop new generation sequencing methods to ensure low cost complete gene sequencing.

[Patient safety in outpatient care - study of Swiss primary care offices]. / Die Patientensicherheit in der Grundversorgung - eine Erhebung in Schweizer Hausarztpraxen.

Knowledge of the most frequent and relevant safety problems is necessary in order to identify areas of risk in patient safety and to specify need for action. For Switzerland, there was no data available that systematically describes the type and frequency of critical incidents in outpatient care. Due to differences in primary care systems world wide, the transfer of international data to the Swiss context is of limited validity. For this reason the Patient Safety Foundation conducted a research project in cooperation with partners from primary care practice. We analysed the frequency and severity of patient safety risks in primary care offices as well as the safety climate in those practices. Results of the survey show the following areas of risk are of high relevance: medication, triage by nurse at initial contact (by phone), diagnosis as well as failures to monitor patients in the office. In addition, errors in tests and therapeutic interventions should be prioritized for future action. Several differences between professional groups could be identified regarding the perception and estimation of critical incidents as with respect to the safety climate. In conclusion, physicians and nurses should be involved when analysing risks and developing measures in order to insure high quality standards in patient care.

A randomized trial on the efficacy of methylphenidate and modafinil for improving cognitive functioning and symptoms in patients with a primary brain tumor.

Limited research is available regarding the efficacy of psychostimulants in treating cognitive function in primary brain tumor patients. An open-label, randomized, pilot trial examined both the general and differential efficacy of 4 weeks of methylphenidate (MPH) and modafinil (MOD) in 24 brain tumor patients. Participants completed cognitive tests and self-report measures of fatigue, sleep disturbance, mood and quality of life at baseline and after 4 weeks.Following stimulant treatment, there was evidence of a beneficial effect on test performance in speed of processing and executive function requiring divided attention. Patients with the greatest deficit in executive function at baseline appeared to derive the greatest benefit following stimulant therapy. Inconsistent, differential effects were found on a measure of attention in favor of MPH and on a measure of processing speed in favor of MOD. There was also evidence of a general beneficial effect on patient-reported measures of fatigue, mood, and quality of life, with no statistically significant differences between treatment arms in these measures over time. The results from this small pilot study should be interpreted with caution, but appear to warrant additional research, in larger study samples, targeting fatigue, processing speed and executive function, and exploring different doses of stimulants. Future studies may also wish to explore the specific patient factors that may be associated with responsiveness to psychostimulant treatment.

A description of a cognitive rehabilitation programme evaluated in brain tumour patients with mild to moderate cognitive deficits.

UNLABELLED: This series of articles for rehabilitation in practice aims to cover a knowledge element of the rehabilitation medicine curriculum. Nevertheless they are intended to be of interest to a multidisciplinary audience. The competency addressed in this article is cognitive rehabilitation. BACKGROUND: There is a paucity of literature on the rationale, design, and content of successful cognitive rehabilitation programmes. In the current paper, we describe in detail a cognitive rehabilitation programme that has previously proven effective in a randomized controlled trial in patients with primary brain tumours. The programme's content may be of practical interest to those working with populations of cognitively impaired patients. Programme: The programme consists of six weekly, individual, 2-hour sessions plus homework, and incorporates both strategy training and attention retraining. The elements were taken from two of the few programmes that are evidence-based. It's design consists of psycho-education, teaching of strategies to compensate for problems in attention, memory and executive functioning in daily life. The retraining was based on the assumption that a target process can be improved by frequently practising exercises. It is focused on attention as intact attention may also be necessary for adequate functioning of other cognitive domains. The hierarchically organized exercises, embedded in a game-like computer program, were tailored to the needs of the individual patient. EVALUATION: Mean total training time was estimated to be 35 hours in seven weeks. Adherence to the programme was high. The majority of the participants found the programme to be (very) useful. However, older participants found the programme more burdensome than younger patients. DISCUSSION: Splitting up and spreading out sessions may increase the feasibility and usefulness of the programme for older participants. Further suggestions for improvements and future studies on this programme are also provided.

ERp57 and PDI: multifunctional protein disulfide isomerases with similar domain architectures but differing substrate-partner associations.

Secretory proteins become folded and acquire stabilizing disulfide bonds in the endoplasmic reticulum (ER). Correct disulfide bond formation is a key step in ER quality control (ERQC). Proteins with incorrect disulfide bonds are recognized by the quality control machinery and are retrotranslocated into the cytosol where they are degraded by the proteasome. The mammalian ER contains 17 disulfide isomerases and at least one of them, ERp57, works in conjunction with the ER lectin-like chaperones calnexin and calreticulin. The targeting of ERp57 to calnexin-calreticulin is mediated by its noncatalytic b' domain, and analogous domains in other disulfide isomerases likely determine their substrate and partner preferences. This review discusses some explanations for the multiplicity of disulfide isomerases and highlights structural differences in the b' domains of PDI and ERp57 as an example of how noncatalytic domains define specialized roles in oxidative folding.

Molecular mechanisms in clathrin-mediated membrane budding revealed through subcellular proteomics.

Subcellular proteomics is a powerful new approach that combines subcellular fractionation and MS (mass spectrometry) to identify the protein complement of cellular compartments. The approach has been applied to isolated organelles and major suborganellar structures and each study has identified known proteins not previously understood to associate with the compartment and novel proteins that had been described only as predicted open-reading frames from genome sequencing data. We have utilized subcellular proteomics to analyse the protein components of CCVs (clathrin-coated vesicles) isolated from adult brain. Accounting for identified fragmented peptides allows for a quantitative assessment of protein complexes associated with CCVs, and the identification of many of the known components of post-fusion synaptic vesicles demonstrates that a main function for brain CCVs is to recycle synaptic vesicles. In addition, we have identified a number of novel proteins that participate in CCV formation and function at the trans-Golgi network and the plasma membrane. Characterization of two of these proteins, NECAP1 and NECAP2, has led to the identification of a new consensus motif that mediates protein interactions with the clathrin adaptor protein 2. These studies highlight the ability of proteomics to reveal new insights into the mechanisms and functional roles of subcellular compartments.

Investigations on the reliability of determining an individual's age from the proximal femur.

In the context of individual identifications the reliable determination of age is important. It has been suggested that the femur is appropriate for reliably determining age and excellent results were indeed claimed but calculated errors of estimation were often missing in the studies. In order to check the reliability and validity for forensic diagnostics, two independent investigators who were not informed of the actual age of the femur specimens evaluated x-ray views of 90 femurs according to methods described in the literature. The results of the two investigators differed by maximally 5 years in 64.4% of all cases examined; the average error of estimation amounted to 10.1-17.0 years. Only one-seventh of all cases examined could be precisely grouped into the 5-year class. Deviations of more than 15 years occurred in nearly one fourth of all cases. In particular, individuals over 50 years of age were estimated as being much younger. We must therefore conclude that the method under examination is only appropriate for rough estimations of age. A more accurate estimation within a five-year interval is only rarely possible.