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Contains fulltext : 291117.pdf (Publisher’s version ) (Open Access) Apathy is common after stroke and has been associated with cognitive impairment. However, causality between post-stroke apathy and cognitive impairment remains unclear. We assessed the course of apathy in relation to changes in cognitive functioning in stroke survivors. Using the Apathy Scale (AS) and cognitive tests on memory, processing speed and executive functioning at six- and 15 months post-stroke we tested for associations between (1) AS-scores and (change in) cognitive scores; (2) apathy course (persistent/incident/resolved) and cognitive change scores. Of 117 included participants, 29% had persistent apathy, 13% apathy resolving over time and 10% apathy emerging between 6-15 months post-stroke. Higher AS-scores were cross-sectionally and longitudinally associated with lower cognitive scores. Relations between apathy and cognitive change scores were ambiguous. These inconsistent relations between apathy and changes in cognition over time suggest that post-stroke apathy does not directly impact cognitive performance. Both these sequelae of stroke require separate attention. 01 januari 2023 12 p.

E-type open-source software inevitably grows in size and complexity over time, and without performing anti-regressive tasks this type of software has a limited lifespan. In this project, a case study of the effect of such anti-regressive tasks is conducted using GrimoireLab Graal as a subject. This process is guided by quality metrics and developer insights. The outcome of this work is a life-cycle of maintenance activities, ultimately resulting in a refactored version of GrimoireLab Graal. After applying anti-regressive actions, commonly used software quality metrics decreased (lower is better). Additionally, after performing an experiment to test the evolution readiness of the software, the complexity of the original software increased significantly, whilst no side effects were measured in the revised software.

Background Acute kidney injury (AKI) is a frequent complication after liver transplantation. Although numerous risk factors for AKI have been identified, their cumulative impact remains unclear. Our aim was therefore to design a new model to predict post-transplant AKI. Methods Risk analysis was performed in patients undergoing liver transplantation in two centres (n = 1230). A model to predict severe AKI was calculated, based on weight of donor and recipient risk factors in a multivariable regression analysis according to the Framingham risk-scheme. Results Overall, 34% developed severe AKI, including 18% requiring postoperative renal replacement therapy (RRT). Five factors were identified as strongest predictors: donor and recipient BMI, DCD grafts, FFP requirements, and recipient warm ischemia time, leading to a range of 0–25 score points with an AUC of 0.70. Three risk classes were identified: low, intermediate and high-risk. Severe AKI was less frequently observed if recipients with an intermediate or high-risk were treated with a renal-sparing immunosuppression regimen (29 vs. 45%; p = 0.007). Conclusion The AKI Prediction Score is a new instrument to identify recipients at risk for severe post-transplant AKI. This score is readily available at end of the transplant procedure, as a tool to timely decide on the use of kidney-sparing immunosuppression and early RRT.

Background & Aims: Liver transplantation (LT) has been proposed as an effective salvage therapy even for the sickest patients with acute-on-chronic liver failure (ACLF). This large collaborative study was designed to assess the current clinical practice and outcomes of patients with ACLF who are wait-listed for LT in Europe. Methods: This was a retrospective study including 308 consecutive patients with ACLF, listed in 20 centres across 8 European countries, from January 2018 to June 2019. Results: A total of 2,677 patients received a LT: 1,216 (45.4%) for decompensated cirrhosis. Of these, 234 (19.2%) had ACLF at LT: 58 (4.8%) had ACLF-1, 78 (6.4%) had ACLF-2, and 98 (8.1%) had ACLF-3. Wide variations were observed amongst countries: France and Germany had high rates of ACLF-2/3 (27-41%); Italy, Switzerland, Poland and the Netherlands had medium rates (9-15%); and the United Kingdom and Spain had low rates (3-5%) (p 4 mmol/L (hazard ratio [HR] 3.14; 95% CI 1.37-7.19), recent infection from multidrug resistant organisms (HR 3.67; 95% CI 1.63-8.28), and renal replacement therapy (HR 2.74; 95% CI 1.37-5.51) were independent predictors of post-LT mortality. During the same period, 74 patients with ACLF died on the waiting list. In an intention-to-treat analysis, 1-year survival of patients with ACLF on the LT waiting list was 73% for ACLF-1 or-2 and 50% for ACLF-3. Conclusion: The results reveal wide variations in the listing of patients with ACLF in Europe despite favourable post-LT survival. Risk factors for mortality were identified, enabling a more pre-cise prognostic assessment of patients with ACLF. Lay summary: Acute-on-chronic liver failure (ACLF) is a severe clinical condition for which liver transplantation is an effective therapeutic option. This study has demonstrated that in Europe, referral and access to liver transplantation (LT) for patients with ACLF needs to be harmonised to avoid inequities. Post-LT survival for patients with ACLF was >80% after 1 year and some factors have been identified to help select patients with favourable outcomes. (C) 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All reserved.

Blindsight refers to the observation of residual visual abilities in the hemianopic field of patients without a functional V1. Given the within- and between-subject variability in the preserved abilities and the phenomenal experience of blindsight patients, the fine-grained description of the phenomenon is still debated. Here we tested a patient with established "perceptual" and "attentional" blindsight (c.f. Danckert and Rossetti, 2005). Using a pointing paradigm patient MS, who suffers from a complete left homonymous hemianopia, showed clear above chance manual localisation of 'unseen' targets. In addition, target presentations in his blind field led MS, on occasion, to spontaneous responses towards his sighted field. Structural and functional magnetic resonance imaging was conducted to evaluate the magnitude of V1 damage. Results revealed the presence of a calcarine sulcus in both hemispheres, yet his right V1 is reduced, structurally disconnected and shows no fMRI response to visual stimuli. Thus, visual stimulation of his blind field can lead to "action blindsight" and spontaneous antipointing, in absence of a functional right V1. With respect to the antipointing, we suggest that MS may have registered the stimulation and subsequently presumes it must have been in his intact half field.

Reframing cognitions is assumed to play an important role in treatment for obsessive–compulsive disorder (OCD). However, there hardly is any empirical support for this assumption, especially for children. The aim of this study was to examine if changing dysfunctional beliefs is a mediating mechanism of cognitive behavioral therapy (CBT) for childhood OCD. Fifty-eight children (8–18 years) with OCD received CBT. Dysfunctional beliefs (OBQ-CV) and OCD severity (CY-BOCS) were measured pre-treatment, mid-treatment, post-treatment, and at 16-week follow-up. Results showed that OCD severity and dysfunctional beliefs decreased during CBT. Changes in severity predicted changes in beliefs within the same time interval. Our results did not support the hypothesis that changing dysfunctional beliefs mediates treatment effect. Future studies are needed to replicate these findings and shed more light on the role of explicit and implicit cognitions in treatment for childhood OCD.

BackgroundThe Dutch-Flemish PROMIS® Upper Extremity (DF-PROMIS-UE) V2.0 item bank was recently developed using Item Response Theory (IRT). Unknown for this bank are: (1) if it is legitimate to calculate IRT-based scores for short forms and Computerized Adaptive Tests (CATs), which requires that the items meet the assumptions of and fit the IRT-model (Graded Response Model [GRM]);(2) if it is legitimate to compare (sub) groups of patients using this measure, which requires measurement invariance; and (3) the precision of the estimated patients’ scores for patients with different levels of functioning and compared to legacy measures. Aims were to evaluate (1) the assumptions of and fit to the GRM, (2) measurement invariance and (3) (comparative) precision of the DF-PROMIS-UE v2.0.MethodsCross-sectional data were collected in Dutch patients with upper extremity disorders. Assessed were IRT-assumptions (unidimensionality [bi-factor analysis], local independence [residual correlations], monotonicity [coefficient H]), GRM item fit, measurement invariance (absence of Differential Item Functioning [DIF] due to age, gender, center, duration, and location of complaints) and precision (standard error of IRT-based scores across levels of functioning). To study measurement invariance for language [Dutch vs. English], additional US data were used. Legacy instruments were the Disability of the Arm, Shoulder and Hand (DASH), the QuickDASH and the Michigan Hand Questionnaire (MHQ).ResultsIn total 521 Dutch (mean age ± SD = 51 ± 17 years, 49% female) and 246 US patients (mean age ± SD = 48 ± 14 years, 69% female) participated. The DF-PROMIS-UE v2.0 item bank was sufficiently unidimensional (Omega-H = 0.80, Explained Common Variance = 0.68), had negligible local dependence (four out of 1035 correlations > 0.20), good monotonicity (H = 0.63), good GRM fit (no misfitting items) and demonstrated sufficient measurement invariance. Precise estimates (Standard Error The DASH displayed better reliability than the DF-PROMIS-UE short form and standard CAT, the QuickDASH displayed comparable reliability. The MHQ-ADL displayed better reliability than the DF-PROMIS-UE short form and standard CAT for T-scores between 28 and 50. For patients with low function, the DF-PROMIS-UE measures performed better.ConclusionsThe DF-PROMIS-UE v2.0 item bank showed sufficient psychometric properties in Dutch patients with UE disorders.

Evidencebased behandelen en het monitoren van behandelresultaten met behulp van objectieve meetinstrumenten zijn belangrijke speerpunten in de jeugd-ggz. Echter, deze werkwijze is nog niet standaard. Implementatie van evidencebased behandelen heeft een positief effect op het behandelresultaat, blijkt uit onderzoek bij volwassenen. In de jeugd-ggz is dit echter nog nauwelijks onderzocht. In dit onderzoek hebben we het resultaat gemeten van een implementatietraject van evidencebased behandelen bij een instelling voor jeugd-ggz. Het implementatietraject bestond uit een intensief scholingsprogramma met als doel a) toename van monitoren van de behandeling door behandelaren, b) verkorting van de behandelduur, en c) verbetering van het behandelresultaat. Er werd een pre-post-design toegepast, waarbij twee client-cohorten vergeleken werden: een baseline-cohort, behandeld voorafgaand aan het scholingsprogramma, en een implementatie-cohort, behandeld een half jaar tot een jaar na de start ervan. Voor het bepalen van het behandelresultaat gebruikten we de Strengths and Difficulties Questionnaire (SDQ) voor clienten jonger dan zeventien jaar en de Outcome Questionnaire 45 (OQ45) voor clienten van zeventien jaar en ouder. De behandelduur werd bepaald in weken, vanaf de eerste behandelsessie tot afsluiting van de behandeling. Het monitoren van behandelingen nam na het scholingsprogramma significant toe (van 47% naar 72%), evenals het behandelresultaat (van een gemiddelde delta T van 3,3 naar een gemiddelde delta T van 6,5). De behandelduur bleef hetzelfde. Ruim een derde van de behandelingen duurde langer dan een jaar. Een implementatietraject middels een intensief scholingsprogramma heeft mogelijk een bijdrage geleverd aan het verbeteren van het behandelresultaat bij een instelling voor jeugd-ggz. Onderzoek naar behandelingen die langer dan een jaar duren is van belang.

The aim of this study was to investigate the impact of hypoxia and hypotension during the agonal phase of donor warm ischemia time (DWIT) on hepatic ischemia/reperfusion injury (IRI) and complications in donation after circulatory death (DCD) liver transplantation. A retrospective single‐center study of 93 DCD liver transplants (Maastricht type III) was performed. DWIT was divided into 2 periods: the agonal phase (from withdrawal of treatment [WoT] until circulatory arrest) and the asystolic phase (circulatory arrest until cold perfusion). A drop to 3000 U/L was considered as severe hepatic IRI. SpO2 dropped within 2 minutes after WoT 13 minutes) had more complications with a higher Comprehensive Complication Index during hospital admission (43.0 versus 32.0; P = 0.002) and 90‐day graft loss (26% versus 6%; P = 0.01), compared with recipients with a short SpO2‐agonal (≤13 minutes). Furthermore, Cox proportional hazard modeling identified a long SpO2‐agonal as a risk factor for longterm graft loss (hazard ratio, 3.30; 95% confidence interval, 1.15‐9.48; P = 0.03). In conclusion, the onset of hypoxia during the agonal phase is related to the severity of hepatic IRI and postoperative complications. Therefore, SpO2

Acute kidney injury (AKI) is a common complication after liver transplantation and more frequently observed when high-risk grafts, such as donation after circulatory death (DCD) grafts are used. Our aim was to investigate the impact of the ischemia periods on development of AKI in DCD liver transplantation.We performed a 2-center retrospective study with 368 DCD graft-recipients. Donor warm ischemia time (DWIT) was divided into agonal phase (withdrawal of life support-cardiac arrest) and asystolic phase (cardiac arrest-start cold perfusion). We introduced a new period of warm ischemia: the combined warm ischemia time (combined WIT), which was defined as the sum of DWIT and recipient WIT.AKI was observed in 65% of the recipients and severe AKI in 41% (KDIGO stage 2/3). The length of combined WIT increased significantly with AKI severity: 61 minutes in recipients without AKI up to 69 minutes in recipients with the most severe form of AKI (P0.001). On multivariable analysis, increasing duration of the combined WIT was associated with an increased risk of developing severe AKI (odds ratio, 1.032 per every extra minute; 95% confidence interval, 1.014-1.051; P0.001). No relation was observed between length of cold ischemia time and severe AKI.Combined WIT is a newly defined period of warm ischemia in DCD liver transplantation. Length of combined WIT is associated with severity of postoperative AKI and should ideally not exceed 60 minutes.

Background This was an 8-year follow-up of an RCT comparing ultrasound-guided foam sclerotherapy (UGFS) with high ligation and surgical stripping (HL/S) of the great saphenous vein (GSV). Methods Patients were randomized to UGFS or HL/S of the GSV. The primary outcome was the recurrence of symptomatic GSV reflux. Secondary outcomes were patterns of reflux according to recurrent varices after surgery, Clinical Etiologic Anatomic Pathophysiologic (CEAP) classification, Venous Clinical Severity Score (VCSS) and EuroQol Five Dimensions (EQ-5D™) quality-of-life scores. Results Of 430 patients originally randomized (230 UGFS, 200 HL/S), 227 (52·8 per cent; 123 UGFS, 103 HL/S) were available for analysis after 8 years. The proportion of patients free from symptomatic GSV reflux at 8 years was lower after UGFS than HL/S (55·1 versus 72·1 per cent; P = 0·024). The rate of absence of GSV reflux, irrespective of venous symptoms, at 8 years was 33·1 and 49·7 per cent respectively (P = 0·009). More saphenofemoral junction (SFJ) failure (65·8 versus 41·7 per cent; P = 0·001) and recurrent reflux in the above-knee GSV (72·5 versus 20·4 per cent; P = 0·001) was evident in the UGFS group. The VCSS was worse than preoperative scores in both groups after 8 years; CEAP classification and EQ-5D® scores were similar in the two groups. Conclusion Surgical stripping had a technically better outcome in terms of recurrence of GSV and SFJ reflux than UGFS in the long term. Long-term follow-up suggests significant clinical progression of venous disease measured by VCSS in both groups, but less after surgery. Registration number: NCT02304146 (http://www.clinicaltrials.gov).

Acute kidney injury (AKI) is frequently observed after donation after brain death (DBD) liver transplantation (LT) and associated with impaired recipient survival and chronic kidney disease. Hepatic ischemia/reperfusion injury (IRI) is suggested to be an important factor in this process. The postreperfusion syndrome (PRS) is the first manifestation of severe hepatic IRI directly after reperfusion. We performed a retrospective study on the relation between hepatic IRI and PRS and their impact on AKI in 155 DBD LT recipients. Severity of hepatic IRI was measured by peak postoperative AST levels and PRS was defined as >30% decrease in MAP ≥1 min within 5 min after reperfusion. AKI was observed in 39% of the recipients. AKI was significantly more observed in recipients with PRS (53% vs. 32%; P = 0.013). Median peak AST level was higher in recipients with PRS (1388 vs. 771 U/l; P < 0.001). Decrease in MAP after reperfusion correlated well with both severity of AKI (P = 0.012) and hepatic IRI (P < 0.001). Multiple logistic regression identified PRS as an independent factor for postoperative AKI (OR 2.28; 95% CI 1.06-4.99; P = 0.035). In conclusion, PRS reflects severe hepatic IRI and predicts AKI after DBD LT. PRS immediately after reperfusion is an early warning sign and creates opportunities to preserve postoperative renal function.

To the Editor: Balamuthia mandrillaris is a free-living ameba that has a worldwide distribution in soil and was first reported in 1990 (1). Approximately 200 B. mandrillaris meningoencephalitis cases have been described, mostly from warm climate areas in South America. Its prevalence in the United States is estimated to be 1 case/year (2). However, B. mandrillaris meningoencephalitis has not been reported in Africa, and only 4 cases have been reported in Europe (3–6). Transmission occurs through the respiratory tract or the skin or by organ transplant, and the incubation period varies from weeks to months after primary infection (7). After an indolent, subacute phase with aspecific symptoms, the amebae invade the central nervous system, and illness rapidly progresses, leading almost invariably to death (7). Because B. mandrillaris is difficult to detect in soil, its specific geographic distribution around the world is unknown and is estimated on the basis of where illnesses have been reported (7). This report addresses fatal B. mandrillaris meningoencephalitis in a woman from the Netherlands who had visited The Gambia. In December 2013, a previously healthy 61-year-old white woman in the Netherlands sought care for fever, headaches, and muscle pains she had experienced for 1 week. That year, she had traveled 4 times to The Gambia, the last visit being 1 month before her hospitalization (Technical Appendix Table 1). After she returned from her visit in September 2013, fatigue, diarrhea, fever, and pustular skin lesions on her back and lower extremities developed. A wound swab culture showed Staphylococcus aureus, for which she was treated successfully with oral clarithromycin and topical fucidin ointment. On admission in December, her physical and neurologic examination results were unremarkable. Malaria was excluded; because of persisting headaches, a cerebral computed tomography scan without contrast was performed but showed no abnormalities. In the following days, high fevers, altered mental status, and nuchal rigidity without focal neurologic deficits developed. Cerebrospinal fluid (CSF) examination showed mononuclear pleocytosis, highly elevated protein levels, and low glucose levels (Technical Appendix Table 2). Serial cerebral computed tomography and magnetic resonance imaging scans showed development of an asymmetric hydrocephalus and diffuse leptomeningeal and subependymal contrast enhancement, especially around the brainstem, without signs of intracerebral mass lesions (Technical Appendix Figure). Presumed diagnosis was tuberculous meningitis, and she was treated with tuberculostatic drugs (isoniazid, rifampin, pyrazinamide, and ethambutol) combined with intravenous acyclovir, ceftriaxone, and co-trimoxazole for other infectious causes of meningoencephalitis. Despite external lumbar and ventricular (both lateral ventricles and fourth ventricle) CSF drainage, her neurologic condition deteriorated. Multiple cranial nerve palsies developed, and she became comatose and died 11 days after admission. Informed consent for postmortem examination was obtained, and macroscopic pathologic examination showed uncal and cerebellar herniation caused by increased intracranial pressure. Microscopic brain tissue examination showed signs of acute granulomatous inflammation, multiple hemorrhagic infarctions, and angiitis in the presence of numerous amebic trophozoites and cysts (Figure), which showed granulomatous hemorrhagic necrotic amebic meningoencephalitis. Real-time PCR and subsequent sequencing on brain biopsy and CSF specimens showed B. mandrillaris to be the causative ameba (8,9). Figure Postmortem pathologic findings for woman in the Netherlands who died of Balamuthia mandrillaris meningoencephalitis after returning from travel to The Gambia. A) Macroscopic coronal central section scan showing hemorrhagic necrotizing lesions of the subependymal, ... The infection could have been acquired in The Gambia or the Netherlands because the patient had intensive soil contact in The Gambia, where she frequently cultivated land, and in the Netherlands, where she worked in glass horticulture. She may have been infected through the skin after contact with contaminated soil, but her skin lesions were atypical for B. mandrillaris, and postmortem examinations failed to identify B. mandrillaris except in the central nervous system. The lack of reported B. mandrillaris cases from Africa might indicate a low number of postmortem examinations and little access to advanced diagnostics, rather than a low environmental prevalence of B. mandrillaris. The few reported cases in Europe might be related to lack of awareness and to clinical signs and symptoms that mimic tuberculous meningitis: a lymphocytic pleocytosis with an elevated protein level and a low glucose level in CSF, together with a hydrocephalus and subependymal and leptomeningeal contrast enhancement on magnetic resonance imaging (10). Also, B. mandrillaris meningoencephalitis imaging findings are often nonspecific, including cerebral edema, hydrocephalus, multiple space-occupying and ring-enhancing lesions, leptomeningeal enhancement, or formation of mycotic aneurysms (2). Furthermore, amebic trophozoites are seldom detected in CSF by microscopy (2,3). Consequently, B. mandrillaris meningoencephalitis could be underdiagnosed, especially where this infection has no or only sporadic reports. B. mandrillaris should be considered in refractory or unexplained cases of meningoencephalitis, even outside the Americas and in immunocompetent patients. Detecting B. mandrillaris by PCR in CSF seems most likely to enable early diagnosis and timely treatment. However, appropriate therapy is not well defined; success has been sparsely reported with the simultaneous use of azoles, flucytosine, pentamidine, sulfazidine, macrolide antimicrobial drugs, phenothiazines, and miltefosine (2,7,10). Technical Appendix. Timeline of relevant events, laboratory investigations during hospitalization, and imaging results for Dutch traveler who died of Balamuthia mandrillaris meningoencephalitis after returning from The Gambia. Click here to view.(248K, pdf)

miRNAs have emerged as promising biomarkers because of their association with cell stress and diseases and their easy detection and stability in many body fluids. Because of the sensitivity, the method of choice to detect miRNAs is quantitative RT-PCR (RT-qPCR). Therapeutics, in particular circulating anticoagulants, are notorious for their inhibitory effect on RT-qPCR–based measurements. The effect of heparin contamination on inhibition of RT-qPCR from miRNAs isolated from urine has, however, never been investigated. We obtained urine samples from healthy controls and from heparinized patients undergoing major surgery (live kidney donation or liver transplantation) (n = 27). Samples were spiked with synthetic miRNAs to monitor RNA loss during workup, and levels of endogenous and spiked-in miRNAs were quantified by RT-qPCR. Endogenous miRNAs in urine were protected from degradation, but levels differed substantially within surgery groups. Variability in detection levels of spiked-in miRNAs was low in nonhospitalized controls, but was high in both surgery groups, and the difference in miRNA levels correlated well with the heparin concentration in urinary samples. Treatment of urinary RNA with heparinase I during RT-qPCR strongly reduced this variation in a dose-dependent manner. Heparinase I should therefore be considered as standard step for detection of miRNA in urine from hospitalized individuals.

Descriptions of critical moments of coaching, defined as exciting, tense, or significant moments from the time spent in the coaching conversation experienced by an executive coach and one of his clients, are analyzed and compared. Positioned within a tradition of analyzing critical-moment descriptions, the study makes use of data collected immediately after mutual coaching sessions. Both coach and client recorded one or more critical moments that had occurred in each coaching session, thereby providing data collected over time and allowing a direct comparison of the coach’s and the client’s critical-moment experiences. Results suggested that in almost half of the descriptions, the coach and the client referred to the same moments as being critical in the coaching sessions. Although the coach mostly described moments of self-doubt as being critical, the client focused on moments of new learning and a positive change in the coaching relationship. The results of this study were consistent with earlier work on critical moments in executive coaching. The study also offers an in-depth analysis of the coaching process over time, as experienced by both client and coach.

Background New minimally invasive treatment modalities, such as ultrasound-guided foam sclerotherapy (UGFS), are becoming more popular. In a multicentre randomized controlled non-inferiority trial, the effectiveness and costs of UGFS and surgery for treatment of the incompetent great saphenous vein (GSV) were compared. Methods Patients with primary great saphenous varicose veins were assigned randomly to either UGFS or surgical stripping with high ligation. Recurrence, defined as reflux combined with venous symptoms, was determined on colour duplex scans at baseline, 3 months, 1 year and 2 years after initial treatment. Secondary outcomes were presence of recurrent reflux (irrespective of symptoms), reduction of symptoms, health-related quality of life (EQ-5D™), adverse events and direct hospital costs. Results Two hundred and thirty patients were treated by UGFS and 200 underwent GSV stripping. The 2-year probability of recurrence was similar in the UGFS and surgery groups: 11·3 per cent (24 of 213) and 9·0 per cent (16 of 177) respectively (P = 0·407). At 2 years, reflux irrespective of venous symptoms was significantly more frequent in the UGFS group (35·0 per cent) than in the surgery group (21·0 per cent) (P = 0·003). Mean(s.d.) hospital costs per patient over 2 years were €774(344) per patient for UGFS and €1824(141) for stripping. Conclusion At 2-year follow-up, UGFS was not inferior to surgery when reflux associated with venous symptoms was the clinical outcome of interest. UGFS has the potential to be a cost-effective approach to a common health problem. Registration numbers: NCT01103258 (http://www.clinicaltrials.gov) and NTR654 (http://www.trialregister.nl).

To examine whether intravenous recombinant tissue plasminogen activator (rt-PA) treatment given in the acute phase of ischaemic stroke has a favourable effect on cognitive and functional outcome at six months post-stroke.The present study included 92 patients with a first-ever symptomatic infarct, of whom 25 (27%) were subjected to rt-PA treatment in the first three hours post-stroke. Multivariate logistic regression analyses adjusted for stroke severity, education, age, and sex were performed to examine whether rt-PA treatment influenced cognitive outcome (assessed with a neuropsychological examination covering 7 cognitive domains), basic ADL independence (modified Barthel Indexor = 19), and instrumental ADL independence (Frenchay Activities Indexor = 15) after six months.The adjusted odds ratio for intact cognition was 1.0 (95% CI 0.2 to 4.3), that for basic ADL outcome 13.5 (95 % CI 1.4 to 129.4) and for instrumental ADL 7.1 (95 % CI 1.2 to 42.2).Our findings suggest that rt-PA treatment is associated with a favourable basic and instrumental ADL outcome, but not with a beneficial cognitive outcome after 6 months.

The spatial differences between the two retinal images, called binocular disparities, can be used to recover the three-dimensional (3D) aspects of a scene. The computation of disparity depends upon the correct identification of corresponding features in the two images. Understanding what image features are used by the brain to solve this binocular matching problem is an important issue in research on stereoscopic vision. The role of colour in binocular vision is controversial and it has been argued that colour is ineffective in achieving binocular vision. In the current experiment subjects were required to indicate the amount of perceived depth. The stimulus consisted of an array of fronto-parallel bars uniformly distributed in a constant sized volume. We studied the perceived depth in those 3D stimuli by manipulating both colour (monochrome, trichrome) and luminance (congruent, incongruent). Our results demonstrate that the amount of perceived depth was influenced by colour, indicating that the visual system uses colour to achieve binocular matching. Physiological data have revealed cortical cells in macaque V2 that are tuned both to binocular disparity and to colour. We suggest that one of the functional roles of these cells may be to help solve the binocular matching problem.

Migrant songbirds are vulnerable to changes in climatic conditions on both the breeding and wintering grounds. For North American Neotropical migrants, the El Nino/Southern Oscillation (ENSO), via its effects on global precipitation and temperature, modulates the productivity of their temperate and tropical terrestrial ecosystems used during the course of their annual cycle. We evaluated how a densely nesting population of yellow warblers Dendroica petechia in a riparian forest in southern Manitoba, Canada, responded to the El Nino/Southern Oscillation (ENSO) between 1992 and 2001. Standardized mist netting was used to estimate apparent annual survival of adults and production of young. Both adult survival and the production of young were positively correlated with the Southern Oscillation Index (SOI). More specifically, values of both these demographic parameters were lowest during El Nino years and highest during La Nina years. These findings demonstrate the influence of climate on populations of Neotropical migrants in North America. The more frequent El Ninos predicted to result from future global climate change could negatively affect populations of yellow warblers and other Neotropical migrants breeding in this region.

Isotache models are being used increasingly to describe the time-dependent compression of soft soils. Parameters are usually obtained from incremental loading compression tests and, in the case of 2D isotache models, triaxial tests as well. It is possible to determine all necessary parameters, including strength parameters, from a constant rate of strain oedometer which also measures lateral stress. This is described in the paper. Some effects of unloading on the form of the isotaches are also presented, and it is shown that to be completely effective, adaptations of existing isotache formulations are necessary.

Heat stroke is a life-threatening condition characterised by hyperthermia leading to multiple organ dysfunction. Acute liver failure is a rare and potentially fatal consequence of heat stroke. Management of heat stroke is mainly supportive but liver transplantation can be considered as the treatment of acute liver failure in heat stroke. However, literature on liver transplantation as a treatment for acute liver failure in heat stroke is scarce. Until now, no cases of liver transplantation for acute liver failure in non-exertional heat stroke have been reported. Here, we present the first case report of a successful liver transplantation in a patient with acute liver failure caused by non-exertional heat stroke after a sauna visit.

Objective: A considerable amount of children with anxiety disorders do not benefit sufficiently from cognitive behavioral treatment. The present study examines the predictive role of child temperament, parent temperament and parenting style in the context of treatment outcome.Method: Participants were 145 children and adolescents (ages 8-18) with DSM-IV-TR anxiety disorders who received a 12-session CBT program and were assessed at pretreatment, posttreatment and three months follow-up. Multiple-regression analyses were used to evaluate the following pretreatment and posttreatment variables as potential predictors of treatment response at follow-up: baseline level of anxiety symptoms, child reported maternal and paternal rearing style (emotional warmth, rejection, and overprotection), parent reported child temperament traits (negative affect, effortful control, and extraversion), and mothers' and fathers' self-report temperament traits.Results: More maternal negative affect and less emotional warmth as perceived by the child before treatment were related to less favorable treatment outcome (accounting for 29% of the variance in anxiety at follow-up). Furthermore, maternal negative affect and children's extraversion measured after treatment also predicted anxiety at follow-up (together accounting for 19% of the variance). Paternal temperament and parenting style were unrelated to treatment outcome, as were children's pretreatment temperament traits.Conclusion: The results suggest that tailoring intervention to include strategies to reduce maternal negative affect and promote an emotional warm rearing style may improve treatment outcome. (C) 2013 Elsevier Ltd. All rights reserved.

The early detection of psychotic disorders is seen to be increasingly important. Authors of recent articles are adopting a phenomenological approach, taking the view that changes in self-experience represent a major prodromal feature of psychotic disorders.To find out what a phenomenological approach can contribute to the study of the early phase of psychotic disorders.We discuss the literature that explores to what extent changes in self-experience are a central phenomenon in the prodromal phase of psychotic disorders. We also present a phenomenological model that explains these changes.Characteristic changes in self-experience during the prodromal phase of psychotic disorders can provide the framework for an empirical, phenomenological explanatory model.In an empirical, phenomenological approach early changes in a patientrsquo;s self-experience are considered to play a central role. There are some indications that semi-structured interviews focusing on changes in a patientrsquo;s self-experience can contribute to the early detection of psychotic disorders.

Negatively valenced thoughts are assumed to play a central role in the development and maintenance of anxiety. However, the role of positive thoughts in anxiety is rather unclear. In the current study we examined the role of negative and positive self-statements in the anxiety level of anxious and non-anxious children. Participants were 139 anxiety disordered children and 293 non-anxious children (8-18 years). Compared to non-anxious children, anxious children reported more negative thoughts, less positive thoughts and lower State of Mind (SUM) ratios (ratio of positive to negative thoughts). Negative thoughts and SOM ratios were the strongest predictors of anxiety level in anxious children; whereas both negative and positive thoughts were the strongest predictors of anxiety level in non-anxious children. To conclude, a lack of positive thoughts might be more than just an epiphenomenon of anxiety level and might deserve a place in the cognitive model of anxiety. (C) 2011 Elsevier Ltd. All rights reserved.

A 15-year-old girl with complex partial epilepsy had subdural electrodes implanted. She was tested on reaching tasks during electrocortical stimulation prior to neurosurgery. MRI showed left mesial parietal dysplasia. Stimulation of the superior parietal cortex (electrode pair 37–45, figure, A) during line bisection and visually guided reaching resulted in movement arrest followed by the arm drifting upward (figure, B, …

Contains fulltext : 77073.pdf (Publisher’s version ) (Closed access) Background: Pain poses a major problem in older adults, specifically for those living in homes for the elderly. Previous research indicates that the presence of pain may be associated with changes in cognitive functions. It is unclear, however, how the reported experience of pain relates to cognitive functioning in elderly people with chronic pain. The present study was intended to examine the relationship between clinical pain experience and neuropsychological status in residents of homes for the elderly.Methods: Forty-one residents suffering from arthritis or arthrosis completed tests measuring memory, processing speed, and executive function. The sensory-discriminative and the affective-motivational aspects of clinical pain were measured. Results: Performance on executive function tests was positively related to self-reported pain experience. No relationship was observed between pain and memory or processing speed performance. Conclusion: The present study shows that executive functioning is related to the severity of subjectively reported pain. Possible explanations for this association are discussed.

The study examined the perception of facial expressions of different emotional intensities in obsessive-compulsive disorder (OCD) subtypes. Results showed that the High Risk Assessment and Checking subtype was more sensitive in perceiving the emotions fear and happiness. This suggests that altered affective processing may underlie the clinical manifestation of OCD.

Patients with left-sided neglect frequently show repetitive behaviour on the ipsilesional side, such as re-markings on cancellation tasks or extensive elaboration on drawings. It is unclear whether these perseverative responses occur as a symptom of hemi-neglect or inattention in general, and/or whether they are related to anatomical brain correlates such as lesion location, lesion side or volume. In a first study, we examined the prevalence and neuropsychological correlates of perseverative responses in 206 subacute stroke patients and 63 healthy controls. Perseverative responses were considered present when there was at least one re-marking on the Star Cancellation, and both the degree and spatial distribution of re-markings were examined. A distinction was made between hemi-neglect and non-lateralized inattention. Spatial and verbal working memory were assessed with the Corsi Block Span and the Digit Span. Verbal and non-verbal executive function was assessed with the Visual Elevator and Letter Fluency. Stroke patients without inattention demonstrated re-markings that were related to executive performance, and the degree of perseveration was equally distributed across the sheet. Hemi-neglect patients but not patients with generalized inattention demonstrated more re-markings than controls, suggesting that a lateralized spatial attention bias triggers the perseverative responses. Patients with left and right hemi-neglect showed the same prevalence of perseveration, but the distribution of re-markings was more lateralized towards the ipsilesional side in patients with right-hemispheric stroke. The degree of perseveration in patients with hemi-neglect was related to the severity of the neglect. The goal of the second study on a subset of patients (n = 127) was to determine the neuroanatomical correlates of perseverative responses in the early phase of stroke. Lesion anatomy was administered by indicating involvement of frontal, parietal, temporal, occipital lobe, caudate nucleus, lenticular nucleus and/or thalamus. Lesion volume was calculated using a manual tracing technique. Lesion analyses indicated that perseverative behaviour is strongly associated with lesions involving the caudate nucleus or the lenticular nucleus, independent of lesion volume. The caudate nucleus was an important correlate of perseveration independent of the presence of hemi-neglect. No association was found between lesion side and perseverative responses, in contrast to previous studies. In conclusion, a stroke involving the basal ganglia and the presence of (left- or right-sided) hemi-neglect are two important associates of perseverative responses in the subacute phase of stroke.

Objective The aim of the present study was to examine the predictive value of cognitive impairment in the acute phase after stroke as a risk factor for long-term (six to ten months after stroke) depressive symptoms (DS) and a reduced quality of life (QOL), independent of demographic and neurological predictors. Methods We evaluated 143 patients within the first 3 weeks post-stroke. Predictor variables included domain-specific cognitive function, demographic data, vascular risk factors, lesion characteristics, and clinical factors. Predictor variables associated with long-term DS (Montgomery ?sberg Depression Rating Scale ≥ 7) and QOL (Stroke-Specific Quality of Life Scale) were identified with multiple logistic and linear regression. Results Long-term DS were independently predicted by cognitive impairment at baseline, DS at baseline, female sex, diabetes mellitus, and previous TIA(s). Cognitive impairment, increasing age, and functional dependence predicted a reduced QOL, whereas hypercholesterolaemia predicted a better QOL. Among all cognitive disorders, unilateral neglect was the greatest risk factor for DS after 6 months, whereas a disorder in visual perception and construction affected QOL the most. Conclusions Cognitive impairment and vascular risk factors are important predictors of long-term DS and QOL after stroke. The prognostic value of cognition suggests a reactive component in the development or continuation of long-term DS.

Type 2 diabetes mellitus (DM2) is associated with moderate cognitive impairment in verbal memory, mental flexibility, and information processing speed, while other cognitive functions remain relatively unaffected.1 Moreover, epidemiological studies have shown that DM2 patients have a twofold increased risk of developing either vascular dementia or Alzheimer’s disease.1,2 In the present study we examined whether mild cognitive impairment (MCI) and “cognitive impairment, no dementia” (CIND)—two concepts that are used to describe cognitive impairment in the transitional state between normal aging and early dementia—can be applied to the cognitive impairments encountered in a population based sample of DM2 patients. Recently, these concepts have attracted considerable attention, as individuals who meet the criteria for either MCI or CIND are known to have a substantially increased risk of developing dementia.3,4 MCI is defined as a memory deficit without impairments in other cognitive domains.3 Patients with MCI develop Alzheimer’s disease at an annual incidence of between 6% and 25%, compared with 0.2–3.9% in the general population of the same age. The broader concept of CIND is used to describe more general cognitive impairments, often encountered in relation to vascular risk factors. The diagnosis requires impairment in one or more cognitive domains and no dementia.5 A fivefold increased risk of developing Alzheimer’s disease, vascular dementia, or mixed Alzheimer/vascular dementia has been reported in patients with CIND.4 If either of the concepts MCI or CIND is …

Objective: To determine whether endogenous sex hormone levels are associated with cognitive functioning in men. Methods: Cognitive performance was assessed in 400 independently living men between ages 40 and 80 in a population-based cross-sectional study. Compound scores were calculated for memory function, processing capacity/speed, and executive function. The Mini-Mental State Examination was used as a measure of global cognitive function. The adjusted association of testosterone (T) and estradiol (E 2) (total, bioavailable) with neuropsychological test scores in the total group and in subgroups was assessed by linear and logistic regression analysis. Results: Curvilinear associations were observed between T and memory performance and processing capacity/speed, suggesting optimal sex hormone levels. No association between E2 and cognitive functioning was found. After the population was subdivided into four age decades, a linear association of T with cognitive functioning in the oldest age category remained. No association was found in the other age decades. Lower bioavailable T levels were associated with lower scores on processing capacity/speed and executive function; β (95% CI) values were 0.36 (0.07 to 0.66) and 0.17 (-0.01 to 0.35). Similar results were observed for total T. Conclusions: Higher testosterone (T) levels are associated with better cognitive performance in the oldest age category. Apparent curvilinear associations between T and certain cognitive functions in men suggest an optimal hormone level for particular cognitive tasks and are explained by linear associations in the oldest age category.

While the Mini-Mental State Examination (MMSE) was originally developed to screen for dementia and delirium, many neurologists use this measure as a screening instrument for 'cognitive impairment' in hospitalized stroke patients. However, the validity of the MMSE as such has never been evaluated in acute stroke. We administered the MMSE in addition to a neuropsychological examination covering six cognitive domains to 34 stroke patients (mean interval between stroke and examination, 6.5+/-2.9 days) and 34 healthy controls. The area under the receiver operating characteristic curve (AUC) was calculated in addition to the sensitivity and specificity for various cut-off points on the MMSE. Seventy percent of the patients were impaired in at least one cognitive domain. The accuracy of the MMSE in detecting cognitive impairment was no better than chance (AUC = 0.67; p = 0.13). No optimum MMSE cut-off value could be identified. The MMSE is particularly insensitive to impairments in abstract reasoning, executive functioning, and visual perception/construction.

Objective: To evaluate the prognostic value of domain-specific cognitive abilities in acute stroke with respect to long-term cognitive and functional outcome in addition to neurologic and demographic predictors. Methods: The authors evaluated 168 patients within the first 3 weeks after first-ever stroke. The prevalence of neuropsychological impairment was calculated vs 75 matched healthy controls. The authors also recorded demographic data, vascular risk factors, lesion characteristics, and clinical factors at admission. Independent predictor variables associated with long-term cognitive impairment (assessed with a follow-up neuropsychological examination) and functional impairment (assessed with the modified Barthel Index and the Frenchay Activities Index) were identified with stepwise multiple logistic regression. Areas under receiver operator characteristic curves were used to compare the predictive value of three models, i.e., a standard medical model, a purely cognitive model, and a model consisting of both medical and cognitive predictors. Results: Thirty-one percent of patients showed long-term cognitive impairment. Basic and instrumental ADL disturbances remained present in 19% and 24% of patients. Domain-specific cognitive functioning predicted cognitive and functional outcome better than any other variable. Moreover, the prediction of instrumental ADL functioning improved when cognitive predictors were added to the standard medical model (p 0.05). Impairments in abstract reasoning and executive functioning were independent predictors of long-term cognitive impairment. Inattention and perceptual disor- ders were more important in predicting long-term functional impairment. Conclusion: Domain-specific cognitive abilities in the early phase of stroke are excellent independent predictors of long-term cognitive and functional outcome. NEUROLOGY 2005;64:821-827

Objective: To examine the relation between depressive symptoms and specific cognitive functions in patients with a recent stroke and to examine associations with lesion characteristics. Methods: We studied 126 of 183 consecutive patients within 3 weeks after a first-ever symptomatic stroke (mean interval, 8.3F4.3 days). Presence and severity of depressive symptoms was assessed with the Montgomery 2sberg Depression Rating Scale. Neuropsychological functioning was examined by means of a detailed neuropsychological examination covering six cognitive domains. We included a healthy control group (N=75) to obtain normative data for the neuropsychological examination. Functional impairment was measured with the modified Barthel Index and the modified Rankin Scale. Symptomatic and preexistent lesion characteristics were determined on CT or MRI. Results: Of the included patients, 40% demonstrated mild and 12% moderate to severe depressive symptoms. Severity of depressive symptoms was related to lesion volume (p=0.008), functional impairment (all pb0.004), and degree of overall cognitive impairment (p=0.005). After adjustment for lesion size, a specific neuropsychological profile emerged in patients with moderate to severe depressive symptoms, affecting primarily memory, visual perception, and language (all pb0.05). No association was found between severity of depressive symptoms and lesion location, presence of preexistent lesions (white matter lesions and silent infarcts), and demographic factors (age, education, and gender). Conclusions: Moderate or severe symptoms of depression in the early stage poststroke are associated with a specific pattern of cognitive impairment, lesion size, and functional status. We suggest that depressive symptoms early after stroke are, at least in part, a reactive phenomenon secondary to severe cognitive and functional deficits. D 2004 Elsevier B.V. All rights reserved.

A 15-year-old-boy and his mother, both carrying a cryptic deletion within 12p13.33, are described. The proband has a mild phenotype with moderate mental retardation and severe behavioural problems. The mother had some learning difficulties at school. Conventional GTL-banded high-resolution chromosome analysis showed normal karyotypes. Subsequent analysis by fluorescence in situ hybridization using a set of probes specific for the subtelomeric regions of all chromosomes, plus a series of probes at 12p13.33 extending from the 12p telomere, showed that both mother and son carry a 1.65 Mb terminal deletion in this region. There are 10 predicted genes within the deleted region. The unanticipated familial nature of the deletion emphasizes the value of family studies in all cases with subtelomeric abnormalities. It also demonstrates the difficulty in making a clinical diagnosis of individuals with this deletion. To the best of the present authors' knowledge, the proband and his mother are the first patients described with a submicroscopic deletion at 12p13.33.

Human spatial memory can be divided into multiple, partly separate cognitive processes. In this study, object location memory was studied using a set of tasks that assessed three different spatial memory aspects: positional memory, object location binding, and a combined process. Also, maze learning and spatial span memory were measured. Ten patients who had undergone intracranial tumour resection participated, and their individual results were compared with control data from 24 healthy subjects. Four patients showed selective spatial memory impairments; two patients were impaired at positional memory, and two other patients were impaired on object location binding and the combined process. This double dissociation provides further evidence for the notion that object location memory is not a unitary system, but consists of at least two separate mechanisms. In addition, spatial memory problems were predominantly present in the patients with lesions in either the right hemisphere or in the parietal lobe. These results are in agreement with previous findings on the involvement of the right hemisphere and the posterior parietal cortices in spatial processing.

Homozygotes for the rare folate-sensitive autosomal fragile sites have never been recorded. Two non-folate-sensitive rare fragile sites (FRA10B and FRA17A) have been previously recorded in normal individuals. We document two unrelated normal individuals who are homozygotes for the rare fragile site FRA16B and record the patterns of induction of this fragile site with berenil. The existence of normal homozygotes for FRA16B suggests that this fragile site is not within a gene essential for normal development.

Three patients with accessory small ring chromosomes derived from chromosome 1 are presented together with additional clinical details and cytogenetic analyses of a previously reported patient. Cytogenetic analysis was undertaken by FISH using a reverse painting probe generated from one of the patients by microdissection of the r(1) chromosome and with a BAC923C6 which maps to 1p12. Results indicated that patients with r(1) chromosomes consisting of 1q12 heterochromatin and short arm pericentric euchromatin which extends to at least the BAC923C6 were associated with a normal or mild phenotype. Patients with abnormal phenotypes possessed two types of rings. One patient had evidence for contiguous pericentric short arm euchromatin which extended from the centromere to beyond the BAC923C6. Two patients showed molecular cytogenetic results which were compatible with non-contiguous chromosome 1 euchromatin. The diversity of origin of r(1)s will hamper attempts to define phenotype/genotype relationships. Keywords: ring chromosome 1; microdissection; chromosome painting

In order to control the quality of rare earth determinations in environmental matrices, the Standards, Measurements and Testing Programme (formerly Community Bureau of Reference, BCR) of the European Commission has started a project, the final aim of which is to certify four types of matrices (tuna muscle, mussel tissue, aquatic plant and estuarine sediment) for their contents of a range of rare earth elements (Sc, Y and the lanthanides: La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb and Lu). The elements U and Th were added to the study. The first part of this project consisted of an interlaboratory study which aimed to test the feasibility of preparation of environmental reference materials and to detect and remove most of the pitfalls observed in rare earth determinations. This paper presents the preparation of the four matrices for the intercomparison study and for the candidate reference material. The main results are presented of the interlaboratory study that was carried out prior to the certification campaign. This collaborative trial is the first attempt ever carried out at this scale to evaluate the state-of-the-art of rare earth determinations in the environment. Its impact on the improvement of chemical measurements will have positive effects on the comparibility of data necessary for environmental monitoring.