Precise predictions for V + jets dark matter backgrounds.

High-energy jets recoiling against missing transverse energy (MET) are powerful probes of dark matter at the LHC. Searches based on large MET signatures require a precise control of the Z ( ν ν ¯ ) +  jet background in the signal region. This can be achieved by taking accurate data in control regions dominated by Z ( ℓ + ℓ - ) +  jet, W ( ℓ ν ) +  jet and γ +  jet production, and extrapolating to the Z ( ν ν ¯ ) +  jet background by means of precise theoretical predictions. In this context, recent advances in perturbative calculations open the door to significant sensitivity improvements in dark matter searches. In this spirit, we present a combination of state-of-the-art calculations for all relevant V +  jets processes, including throughout NNLO QCD corrections and NLO electroweak corrections supplemented by Sudakov logarithms at two loops. Predictions at parton level are provided together with detailed recommendations for their usage in experimental analyses based on the reweighting of Monte Carlo samples. Particular attention is devoted to the estimate of theoretical uncertainties in the framework of dark matter searches, where subtle aspects such as correlations across different V +  jet processes play a key role. The anticipated theoretical uncertainty in the Z ( ν ν ¯ ) +  jet background is at the few percent level up to the TeV range.

Etomidate activates epileptic high frequency oscillations.

OBJECTIVE: The short acting anesthetic etomidate has been shown to provoke epileptic spikes and rarely seizures. Influence of etomidate on the occurrence of epileptic HFO (high frequency oscillations) however is unknown. An HFO inducing effect of etomidate would allow further validation of the substance as a provocation measure in presurgical evaluation as well as provide insights into the common mechanisms of HFO, spike and seizure generation. METHODS: We retrospectively analyzed EEG data from four patients who underwent etomidate activation during invasive video-EEG monitoring with subdural strip electrodes. Spikes were manually selected in raw data, HFO in band pass filtered data (80-250Hz). Rate and spatial distribution of HFO and spikes in three segments were compared: immediately after etomidate administration, as well as during slow wave sleep and while awake. RESULTS: Rates of HFO and spikes increased significantly after etomidate administration: Overall average rates of spikes were 9.7/min during sleep, 10/min while awake and 61.4/min after etomidate. Average HFO rates were 9.5/min during sleep, 8.3/min while awake and 24.4/min after etomidate (p<0.001, non-parametric ANOVA). Spatial distributions of HFO and spikes after administration of etomidate were consistent with the seizure onset zone (SOZ) and area of resection when available (SOZ: two patients; resection: one patient; no information: one patient). Except for spurious events, no additional HFO and spike foci were seen with activation. CONCLUSIONS: Etomidate administration activates spikes and HFO. Spatial distributions do not extend beyond electrodes showing spikes and HFO without Etomidate and seem consistent with the epileptic network. SIGNIFICANCE: Etomidate activation is a safe procedure to provoke not only epileptic spikes but also HFO, which were shown to have a high specificity for the SOZ.

Regulation of cell cycle checkpoint kinase WEE1 by miR-195 in malignant melanoma.

WEE1 kinase has been described as a major gate keeper at the G2 cell cycle checkpoint and to be involved in tumour progression in different malignant tumours. Here we analysed the expression levels of WEE1 in a series of melanoma patient samples and melanoma cell lines using immunoblotting, quantitative real-time PCR and immunohistochemistry. WEE1 expression was significantly downregulated in patient samples of metastatic origin as compared with primary melanomas and in melanoma cell lines of high aggressiveness as compared with cell lines of low aggressiveness. Moreover, there was an inverse correlation between the expression of WEE1 and WEE1-targeting microRNA miR-195. Further analyses showed that transfection of melanoma cell lines with miR-195 indeed reduced WEE1 mRNA and protein expression in these cells. Reporter gene analysis confirmed direct targeting of the WEE1 3' untranslated region (3'UTR) by miR-195. Overexpression of miR-195 in SK-Mel-28 melanoma cells was accompanied by WEE1 reduction and significantly reduced stress-induced G2-M cell cycle arrest, which could be restored by stable overexpression of WEE1. Moreover, miR-195 overexpression and WEE1 knockdown, respectively, increased melanoma cell proliferation. miR-195 overexpression also enhanced migration and invasiveness of melanoma cells. Taken together, the present study shows that WEE1 expression in malignant melanoma is directly regulated by miR-195. miR-195-mediated downregulation of WEE1 in metastatic lesions may help to overcome cell cycle arrest under stress conditions in the local tissue microenvironment to allow unrestricted growth of tumour cells.

Vocational perspectives after spinal cord injury.

OBJECTIVE: To give insight into the vocational situation several years after a traumatic spinal cord injury (SCI) and describe the personal experiences and unmet needs; to give an overview of health and functional status per type of SCI and their relationship with employment status. DESIGN: Descriptive analysis of data from a questionnaire. SETTING: Dutch rehabilitation centre with special department for patients with spinal cord injuries. SUBJECTS: Fifty-seven patients with a traumatic SCI, aged 18-60 years, admitted to the rehabilitation centre from 1990 to 1998. MAIN MEASURES: Questionnaire with items related to vocational outcome, job experiences, health and functional status. RESULTS: Of 49 patients who were working at the moment of SCI 60% currently had a paid job. Vocational outcome was related to a higher educational level. A significant relation between the SCI-specific health and functional status and employment was not found. The respondents who changed to a new employer needed more time to resume work, but seemed more satisfied with the job and lost fewer working hours than those who resumed work with the same employer. In spite of reasonable to good satisfaction with the current work situation, several negative experiences and unmet needs were reported. CONCLUSIONS: Despite a high participation in paid work following SCI, the effort of the disabled worker to have and keep a job should not be underestimated.

Participation and satisfaction after spinal cord injury: results of a vocational and leisure outcome study.

STUDY DESIGN: Survey. OBJECTIVES: Insight in (1) the changes in participation in vocational and leisure activities and (2) satisfaction with the current participation level of people with spinal cord injuries (SCIs) after reintegration in society. DESIGN: Descriptive analysis of data from a questionnaire. SETTING: Rehabilitation centre with special department for patients with SCIs, Groningen, The Netherlands. SUBJECTS: A total of 57 patients with traumatic SCI living in the community, who were admitted to the rehabilitation centre two to 12 years before the current assessment. MAIN OUTCOME MEASURES: Changes in participation in activities; current life satisfaction; support and unmet needs. RESULTS: Participation expressed in terms of hours spent on vocational and leisure activities changed to a great extent after the SCI. This was mainly determined by a large reduction of hours spent on paid work. While 60% of the respondents successfully reintegrated in work, many changes took place in the type and extent of the job. Loss of work was partially compensated with domestic and leisure activities. Sports activities were reduced substantially. The change in participation level and compensation for the lost working hours was not significantly associated with the level of SCI-specific health problems and disabilities. As was found in other studies, most respondents were satisfied with their lives. Determinants of a negative life satisfaction several years following SCI were not easily indicated. Reduced quality of life was particularly related to an unsatisfactory work and leisure situation. CONCLUSIONS: Most people with SCI in this study group were able to resume work and were satisfied with their work and leisure situation.

[Nitrous oxide. Sense or nonsense for today's anaesthesia]. / Lachgas. Sinn oder Unsinn für die heutige Narkoseführung.

Nitrous oxide has been used in addition to other volatile anaesthetics to provide general anaesthesia and short time sedation for more than 150 years. However, the exact mechanisms of action remain unclear. For decades nitrous oxide was considered to be the ideal anaesthetic because of his favourable physical properties and low cardiovascular side effects. However, the known side effects of nitrous oxide as well as the implementation of new anaesthetic agents and short acting opiates led to more and more criticism about the administration of this gas. Nitrous oxide is still frequently used for mask induction primarily in paediatric anaesthesia and gynaecology. However, recent studies have shown that omitting nitrous oxide can also be a risk factor because of an increased susceptibility to intraoperative awareness. Careful consideration of the illustrated contraindications and side effects as well as the available alternatives, shows that nitrous oxide is still an option in general anaesthesia.

Vocational reintegration following spinal cord injury: expectations, participation and interventions.

STUDY DESIGN: Survey. OBJECTIVES: To explore the process of reintegration in paid work following a traumatic spinal cord injury (SCI), including the role of early expectations of individual patients regarding return to work, indicators of success of job reintegration and a description of reintegration interventions and barriers. SETTING: Dutch rehabilitation centre with special department for patients with spinal cord injuries. METHODS: Descriptive analysis of data gathered by a mailed questionnaire, which was returned by 57 persons (response 83%) with traumatic SCI, aged 18-60 years, and data of earlier expectations reported by the individual patients during the rehabilitation admission following SCI from 1990 to 1998. RESULTS: Of 49 respondents who were employed at the moment of the SCI, 45% expected to be able to resume work. These positive expectations were associated with a higher educational level. In 67%, return to work was successful. The chance to reintegrate successfully was better if the patient expected to resume work. Logistic regression analysis did not reveal other significant indicators. About one-third of the 49 respondents working preinjury followed vocational retraining, which was successful for most of them so far. In the majority of work situations modifications have been made, such as job adaptations and reduction of working hours. Several unmet needs regarding reintegration interventions were also reported. CONCLUSIONS: Positive expectations regarding resumption of work after a SCI are an important indicator of successful reintegration in work. An active role of the rehabilitation team is recommended in drawing up a vocational reintegration plan to prepare the patient, the employer and professionals involved in the reintegration process.

Prediction of functional outcome after spinal cord injury: a task for the rehabilitation team and the patient.

STUDY DESIGN: Descriptive analysis of data gathered in an information system. OBJECTIVES: To explore the predictions of professionals and patients regarding functional outcome after spinal cord injury related to the final results after inpatient rehabilitation, in order to make prognostics of rehabilitation outcome more successful and enlarge the role of the patient in selecting realistic rehabilitation goals. METHODS: Data from 55 patients with spinal cord injury admitted to the rehabilitation centre. Expectations of the rehabilitation team and the patients regarding future independence in performing six daily activities were compared to the functional results at discharge. The results of patients with different level and extent of lesion were analyzed. RESULTS: In 52% of all performed skills, independence was achieved at discharge. Professionals and patients made similar predictions. If they both expected independence after rehabilitation. 90% of the skills were performed independently at discharge. If they both did not expect independence only 3% of the functional results were positive. Of all combined predictions 64% was correct. Correct predictions were most often found regarding self-care skills of patients with paraplegia and regarding mobility of patients with complete lesions. Prediction of self-care outcome of patients with tetraplegia is far more complicated. There was a considerable variation in predictions of mobility potential, especially regarding patients with incomplete lesions. If the team and patients agreed upon expected independence in mobility skills of these patients, the final results were mostly positive. CONCLUSIONS: Prediction of functional outcome after spinal cord injury was most successful if the expectations of the team and patients were combined. Prognosis of self-care outcome of patients with paraplegia and mobility potential of patients with complete spinal cord lesions was usually clear at admission. However, selection of realistic goals concerning self-care skills of patients with tetraplegia and mobility skills of patients with incomplete lesions is far more complicated. Gradual adjustment of objectives is needed during the rehabilitation process in close collaboration between the professionals and the patients.

Functional outcome of patients with spinal cord injury: rehabilitation outcome study.

OBJECTIVE: To increase our knowledge of neurological recovery and functional outcome of patients with spinal cord injuries in order to make more successful rehabilitation programmes based on realistic goals. DESIGN: Descriptive analysis of data gathered in an information system. SETTING: Rehabilitation centre in The Netherlands with special department for patients with spinal cord injuries. SUBJECTS: Fifty-five patients with traumatic spinal cord lesions admitted to the rehabilitation centre from 1988 to 1994. MAIN OUTCOME MEASURES: The functional improvement was presented in terms of progress in independence in nine daily activity skills. Independence was rated on a four-point scale. RESULTS: From admission to discharge, lesions in 100% of patients with tetraplegia and 96% of patients with paraplegia remained complete. Significant progress in independence was made in self-care, ambulation and bladder and bowel care. Differences were found in the extent of functional improvement between subgroups of patients with different levels and extent of lesion. Contrary to expectations based on theoretical models, patients with complete paraplegia did not achieve maximal independence in self-care. Independent walking was only attained by patients with incomplete lesions. Regarding outcome of bladder and bowel care, poor results were found, especially the independence in defaecation and toilet transfers. CONCLUSIONS: The results of this study provided more insight into the functional outcome of a group of patients with traumatic spinal cord injury. More research is needed to evaluate the rehabilitation programmes for these patients.

Rehabilitation of patients with spinal cord lesions in The Netherlands: an epidemiological study.

Very little is known about the occurrence of spinal cord lesions and results of the rehabilitation of patients with such lesions in the Netherlands. This study was conducted to describe the process of rehabilitation in the Dutch situation, to assess the incidence of spinal cord lesions in a regional rehabilitation centre and to characterise differences between traumatic and non-traumatic spinal cord lesions regarding age, level and extent of lesion. In this study 293 patients were included who were admitted to the rehabilitation centre between 1982 and 1993. Sixty-six per cent of this group came from the university hospital. The mean length of stay in the rehabilitation centre was 154 days. After completing the rehabilitation programme 94% of patients went home. Sixteen new SCI patients per million per year were admitted to the rehabilitation centre. Of our group 52% had a non-traumatic lesion, which concerned older patients with more incomplete lesions. In our opinion close collaboration between the university hospital and the rehabilitation centre is needed for optimal rehabilitation. Attention to independent living programmes and appropriate housing facilities can shorten the length of stay and increase the number of discharges of patients to their own environment. For patients with non-traumatic spinal cord lesions special programmes should be made available.