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Background: Carotid atherosclerosis is associated with cognitive impairment and dementia, though there is limited evidence of a direct link between carotid disease and amyloid-β (Aβ) burden. Objective: We studied the association of baseline and progressive carotid intima media thickness (CIMT) with Aβ on 11C-Pittsburgh Compound B (PiB) to determine if those with carotid atherosclerosis would have higher Aβ burden. Methods: We studied 47 participants from the Framingham Offspring cohort with carotid ultrasounds measuring CIMT at their 6th clinic examination (aged 49.5±5.7 years) and an average of 9.6 years later, and PiB imaging measuring Aβ on average 22.1 years post baseline. We used multivariate linear regression analyses to relate baseline, follow-up, mean, and progression of internal carotid artery (ICA) and common carotid artery (CCA) CIMT to Aβ in brain regions associated with Alzheimer’s disease (AD) and related dementias (ADRD), adjusting for age, sex, and other vascular risk factors. Results: Participants with higher mean ICA IMT had more Aβ in the precuneus (beta±standard error [β±SE]: 0.466±0.171 mm, p = 0.01) and the frontal, lateral, and retrosplenial regions (β±SE: 0.392±0.164 mm, p = 0.022) after adjusting for age, sex, vascular risk factors, and medication use. We did not find an association between any CCA IMT measures and Aβ or progression of ICA or CCA IMT and Aβ. Conclusion: Carotid atherosclerosis, as measured by ICA IMT, is associated with increased Aβ burden later in life. These findings support a link between vascular disease and AD/ADRD pathophysiology.

Background: Liver steatosis and fibrosis are emerging as risk factors for multiple extrahepatic health conditions; however, their relationship with Alzheimer’s disease pathology is unclear. Objective: To examine whether non-alcoholic fatty liver disease (NAFLD) and FIB-4, a non-invasive index of advanced fibrosis, are associated with brain amyloid-β (Aβ) and tau pathology. Methods: The study sample included Framingham Study participants from the Offspring and Third generation cohorts who attended exams 9 (2011–2014) and 2 (2008–2011), respectively. Participants underwent 11C-Pittsburgh Compound-B amyloid and 18F-Flortaucipir tau positron emission tomography (PET) imaging and abdomen computed tomography, or had information on all components of the FIB-4 index. Linear regression models were used to assess the relationship of NAFLD and FIB-4 with regional tau and Aβ, adjusting for potential confounders and multiple comparisons. Results: Of the subsample with NAFLD information (N = 169; mean age 52±9 y; 57% males), 57 (34%) had NAFLD. Of the subsample with information on liver fibrosis (N = 177; mean age 50±10 y; 51% males), 34 (19%) had advanced fibrosis (FIB-4 > 1.3). Prevalent NAFLD was not associated with Aβ or tau PET. However, FIB-4 index was significantly associated with increased rhinal tau (β= 1.03±0.33, p = 0.002). Among individuals with prevalent NAFLD, FIB-4 was related to inferior temporal, parahippocampal gyrus, entorhinal and rhinal tau (β= 2.01±0.47, p

Background: Depressive symptoms predict increased risk for dementia decades before the emergence of cognitive symptoms. Studies in older adults provide preliminary evidence for an association between depressive symptoms and amyloid-β (Aβ) and tau accumulation. It is unknown if similar alterations are observed in midlife when preventive strategies may be most effective. Objective: The study aim was to evaluate the association between depressive symptoms and cerebral Aβ and tau in a predominately middle-aged cohort with examination of the apolipoprotein (APOE) ɛ4 allele as a moderator. Methods: Participants included 201 adults (mean age 53±8 years) who underwent 11C-Pittsburgh Compound B amyloid and 18F-Flortaucipir tau positron emission tomography (PET) imaging. Depressive symptoms were evaluated with the Center for Epidemiological Studies Depression Scale (CES-D) at the time of PET imaging, as well as eight years prior. Associations between depressive symptoms at both timepoints, as well as depression (CES-D≥16), with regional Aβ and tau PET retention were evaluated with linear regression adjusting for age and sex. Interactions with the APOE ɛ4 allele were explored. Results: Depressive symptoms and depression were not associated with PET outcomes in the overall sample. However, among APOE ɛ4 allele carriers, there was a significant cross-sectional association between depressive symptoms and increased tau PET uptake in the entorhinal cortex (β= 0.446, SE = 0.155, p = 0.006) and amygdala (β= 0.350, SE = 0.133, p = 0.012). Conclusion: Although longitudinal studies are necessary, the results suggest that APOE ɛ4 carriers with depressive symptoms may present with higher susceptibility to early tau accumulation in regions integral to affective regulation and memory consolidation.

IMPORTANCE: Aortic stiffness is associated with clinical hallmarks of Alzheimer disease and related dementias and could be a modifiable target for disease prevention. OBJECTIVE: To assess associations of aortic stiffness and pressure pulsatility with global amyloid-β plaques and regional tau burden in the brain of middle-aged and older adults without dementia. DESIGN, SETTING, AND PARTICIPANTS: The sample for this cross-sectional study was drawn from the Framingham Heart Study Third Generation Cohort at examination 3 (N = 3171; 2016-2019), of whom 3092 successfully underwent comprehensive hemodynamic evaluations. In a supplemental visit (2015-2021), a subset of 270 participants without dementia who represented the spectrum of vascular risk also underwent positron emission tomography. Thirteen participants were excluded for missing covariate data. The final sample size was 257 participants. EXPOSURES: Three measures of aortic stiffness and pressure pulsatility (carotid-femoral pulse wave velocity, central pulse pressure [CPP], and forward wave amplitude [FWA]) were evaluated using arterial tonometry. MAIN OUTCOMES AND MEASURES: Global amyloid-β plaques and regional tau were assessed using (11)C-Pittsburgh compound B and (18)F-flortaucipir positron emission tomography tracers, respectively. RESULTS: The mean (SD) age of the 257 participants was 54 (8) years, and 126 were women (49%). All participants were White Western European race. In multivariable models, higher CPP (β per SD = 0.17; 95% CI, 0.00-0.35; P = .045) and FWA (β per SD = 0.16; 95% CI, 0.00-0.31; P = .04) were associated with greater entorhinal tau burden. In similar models, higher CPP (β per SD = 0.19; 95% CI, 0.02-0.36; P = .03) and FWA (β per SD = 0.17; 95% CI, 0.01-0.32; P = .03) were associated with greater rhinal tau burden. Aortic stiffness and pressure pulsatility measures were not associated with amygdala, inferior temporal, precuneus tau burden, or global amyloid-β plaques. Associations for entorhinal and rhinal tau outcomes were more prominent in older participants (≥60 years). For example, higher levels of all aortic stiffness and pressure pulsatility measures (β per SD = 0.40-0.92; P = .001-.02) were associated with higher entorhinal tau burden among older but not younger participants in stratified analyses. CONCLUSIONS AND RELEVANCE: In this cross-sectional study, abnormal central vascular hemodynamics were associated with higher tau burden in specific brain regions. Findings suggest that aortic stiffness, which is potentially modifiable, may be a probable independent target for prevention of tau-related pathologies.

PURPOSE Clinical stage I (CSI) nonseminoma (NS) is a disease limited to the testis without metastases. One treatment strategy after orchiectomy is adjuvant chemotherapy. Little is known about the outcome of patients who experience relapse after such treatment. PATIENTS AND METHODS Data from 51 patients with CSI NS who experienced a relapse after adjuvant bleomycin, etoposide, and cisplatin (BEP) from 18 centers/11 countries were collected and retrospectively analyzed. Primary outcomes were overall and progression-free survivals calculated from day 1 of treatment at first relapse. Secondary outcomes were time to, stage at, and treatment of relapse and rate of subsequent relapses. RESULTS Median time to relapse was 13 months, with the earliest relapse 2 months after start of adjuvant treatment and the latest after 25 years. With a median follow-up of 96 months, the 5-year PFS was 67% (95% CI, 54% to 82%) and the 5-year OS was 81% (95% CI, 70% to 94%). Overall, 19 (37%) of 51 relapses occurred later than 2 years. Late relapses were associated with a significantly higher risk of death from NS (hazard ratio, 1.10 per year; P = .01). Treatment upon relapse was diverse: the majority of patients received a combination of chemotherapy and surgery. Twenty-nine percent of patients experienced a subsequent relapse. At last followup, 41 patients (80%) were alive and disease-free, eight (16%) had died of progressive disease, and one patient (2%) each had died from therapy-related or other causes. CONCLUSION Outcomes of patients with relapse after adjuvant BEP seem better compared with patients who experience relapse after treatment of metastatic disease but worse compared with those who have de-novo metastatic disease. We found a substantial rate of late and subsequent relapses. There seem to be three patterns of relapse with different outcomes: pure teratoma, early viable NS relapse (, 2 years), and late viable NS relapse (. 2 years). © 2019 by American Society of Clinical Oncology

Different types of hysteresis commonly observed in gas adsorption isotherms of metal-organic frameworks (MOFs) and possible reasons are discussed. The temperature effect of hydrogen (H 2 ) and carbon dioxide (CO 2 ) adsorption/desorption hysteresis in an ultramicroporous MOF and a method to obtain accurate isosteric heats of adsorption in small-pore adsorbent materials are presented.

Resume Introduction L’encephalite a anticorps anti-recepteur N-methyl- d -aspartate (Ac anti-NMDA-R) est une entite encore peu connue des pediatres et vraisemblablement sous-diagnostiquee alors que le pronostic vital et cognitif est en jeu. L’utilisation d’immunomodulateurs comme le rituximab a permis des guerisons spectaculaires, mais plusieurs questions demeurent quant a son mode d’action dans ce type d’affection. Cas clinique Une enfant de 6 ans sans antecedent a ete hospitalisee pour un etat de mal epileptique. Des troubles du sommeil et du comportement avaient precede celui-ci de quelques semaines. Progressivement, l’enfant etait devenue grabataire et mutique avec des dyskinesies a predominance bucco-faciales. La ponction lombaire et l’imagerie par resonance magnetique cerebrale etaient normles et le diagnostic a ete etabli par la mise en evidence d’Ac anti-NMDA-R dans le liquide cephalorachidien. Apres elimination d’une origine paraneoplasique, l’enfant a initialement ete traitee par immunoglobulines intraveineuses puis par echanges plasmatiques et enfin par rituximab. La guerison a ete obtenue sous rituximab malgre une recuperation anormalement precoce du nombre de lymphocytes B. Discussion L’encephalite a Ac anti-NMDA-R est une entite de description recente, y compris chez l’enfant. Elle peut etre reversible et sans sequelles si elle est diagnostiquee et traitee precocement. L’utilisation d’immunomodulateurs comme le rituximab semble benefique. Un monitoring immunologique accru serait utile pour mieux apprehender les mecanismes d’action dans les affections auto-immunes du systeme nerveux chez l’enfant.

Background: Surgical simulation training offers trainees the opportunity to practice surgical skills before entering the operating room. The objectives of this study were to determine the effect of simulation for learning instruments for burr hole surgery and whether this learning is translated to real instrument recognition with retention. Methods: Randomized trials of PGY1 neurosurgery residents and perioperative nurses were conducted, using PeriopSim™ for instrument recognition, as well as real instruments. Group A performed simulation tasks using PeriopSim™ prior to identifying real instruments, whereas Group B identified real instruments prior to performing simulation tasks. Nurses’ recall was assessed at seven days. Results: Sixteen residents and 100 nurses were recruited. All participants showed significant overall improvement in their scores for simulated tasks. Group A demonstrated enhanced accuracy and speed of identifying real instruments compared with Group B (pConclusions: Our results demonstrate that recognition of surgical instruments improves with repeated use of the PeriopSim™ platform. Instrument knowledge acquired through simulation training results in improved identification and retained recognition of real instruments.

Background: Patients who require hospitalization for a mild or moderate traumatic brain injury (TBI) are often discharged home with uncertainty around their full recovery. This study examines the frequency and severity of common post-TBI symptoms, as assessed by the Rivermead Post-Concussion Symptoms Questionnaire (RPCQ). Methods: All adult TBI inpatients discharged home from the Neurosurgery service were interviewed by phone at two weeks by a rehab-based nurse practitioner. RPCQ components (cognitive, emotional, and somatic) were analyzed; findings and management recommendations were communicated to family practitioners and the treating neurosurgeon. Results: In 46 patients, cognitive symptoms were present in 52%, 91% had somatic, and 100% had emotional symptoms. Fatigue was the most common symptom (67%). Double vision was the least common symptom (4%). Recommendations for managing symptoms, return to work, and need for formal clinical assessment were provided for 37% of cases. Conclusions: All patients admitted to neurosurgery with mild or moderate TBI had symptoms at two weeks. The RPCQ is a low-cost structured evaluative tool which highlights needs and provides guidance for patients and care-givers; it also seems effective in identifying those who may require formal clinical assessment.

La gammagraphie (egalement appelee tir radiographique) de soudures est une operation non destructive efficace, mais qui peut etre dangereuse si elle n’est pas pratiquee dans le respect d’un corpus de regles precises et contraignantes. La zone de tirs doit etre delimitee de facon a en interdire l’acces a toute personne non habilitee. EDF œuvre a l’elimination des risques via differents leviers (materiel adapte, bonnes pratiques) tout en integrant au mieux les tirs vis-a-vis des autres operations de maintenance, afin d’augmenter la disponibilite de son parc nucleaire de production d’electricite. Cet article explore un axe original d’analyse de l’activite de tirs radiographiques : l’influence des representations de l’espace de travail et de ses utilisations. Cet article pose l’utilisation de certaines contraintes de l’espace comme elements explicatifs de difficultes dans l’activite de balisage et de realisation des tirs. Nous proposons des analyses innovantes a partir d’observations de terrain et d’une analyse theorique provenant des sciences cognitives, completees par des propositions techniques.

We investigated the effect on neuromuscular properties of the knee extensors of an exhaustive cycling exercise performed at 6AM and 6PM. Eleven well trained cyclists performed a maximal aerobic exercise consisting in a sustained effort at 95% of their maximal power until exhaustion (T lim ). Isometric maximal voluntary contraction (MVC) and electromyographic activities (root mean square: RMS) of the vastus lateralis were recorded before (pre-test) and immediately after (post-test) the cycling exercise. The MVC/RMS ratio was calculated and used as an index of neuromuscular efficiency (NME). Rectal temperature was recorded continuously throughout the test session. Results show that Turn cycling exercise was not time-of-day dependent (p = 0.42). A significant interaction effect of time of day and the cycling exercise was demonstrated for MVC (p < 0.02) and NME (p < 0.05). In pre-test, MVC and NME were higher in the late afternoon than in the morning (+6.8%); however both parameters were more affected by the Tiim exercise at 6PM than at 6AM. These results suggest that following cycling Turn exercise, neuromuscular properties of the knee extensors are more affected in the evening than in the morning. However, circadian rhythm of some biomechanical parameters implicated in the pedalling movement may modulate the effect of these diurnal variations.

In hypertension, increased peripheral vascular resistance results from vascular dysfunction with or without structural changes (vessel wall remodeling and/or microvascular rarefaction). Humans with lower birth weight exhibit evidence of vascular dysfunction. The current studies were undertaken to investigate whether in utero programming of hypertension is associated with in vivo altered response and/or abnormal vascular structure. Offspring of Wistar dams fed a normal (CTRL) or low (LP)-protein diet during gestation were studied. Mean arterial blood pressure response to ANG II was significantly increased, and depressor response to sodium nitroprusside (SNP) infusions significantly decreased in male LP adult offspring relative to CTRL. No arterial remodeling was observed in male LP compared with CTRL offspring. Capillary and arteriolar density was significantly decreased in striated muscles from LP offspring at 7 and 28 days of life but was not different in late fetal life [ day 21 of gestation (E21)]. Angiogenic potential of aortic rings from LP newborn (day of birth, P0) was significantly decreased. Striated muscle expressions (Western blots) of ANG II AT1 receptor subtype, endothelial nitric oxide synthase, angiopoietin 1 and 2, Tie 2 receptor, vascular endothelial growth factor and receptor, and platelet-derived growth factor C at E21 and P7 were unaltered by antenatal diet exposure. In conclusion, blood pressure responses to ANG II and SNP are altered, and microvascular structural changes prevail in this model of fetal programming of hypertension. The capillary rarefaction is absent in the fetus and appears in the neonatal period, in association with decreased angiogenic potential. The study suggests that intrauterine protein restriction increases susceptibility to postnatal factors resulting in microvascular rarefaction, which could represent a primary event in the genesis of hypertension.

In recent years, the measurement of flow velocity of the plasma in the edge of tokamaks has gained in importance. The determination of this parameter is often done using electrostatic probe systems such as Mach probes or Gundestrup probes. A Gundestrup system was recently commissioned in Tore Supra. The perpendicular ( U ⊥ ) and parallel ( U // ) components of the velocity are determined from the six ion saturation currents using a neural network. The neural network was trained using ion saturation currents obtained from a two-dimensional kinetic code developed at Tore Supra. We will describe the Gundestrup probe and the neural network training, validation and implementation. Preliminary measurements in ergodic divertor discharges show U // and U ⊥ profiles that exhibit small-scale spatial modulations similar to those reported for the temperature profiles.

Background: Chronic subdural hematomas (cSDH) are a common neurosurgical problem with significant morbidity and mortality. Current treatment methods are variable. Post-operative subdural drain used in conjunction with burr-hole craniostomy may reduce recurrence. This study compared recurrence rates for cSDH between two surgical practices with and without use of post-operative subdural drain at the QEII Health Sciences Center. Methods: A retrospective chart review was conducted to compare recurrence rates between surgical patients treated with or without a post-operative drain between 1997- 2012. The primary endpoint was recurrence, defined as occurrence of symptoms due to hematoma confirmed by CT within six months of the original operation. Categorical frequencies were compared with chi square or Fisher’s exact test. Logistic regression was performed to identify risk factors for recurrence. Results: There were 85 patients (mean age 73 years; SD 13.0) who had burr-hole craniostomy. Age, cSDH volume, site, GCS, anticoagulation, drain, conservative treatment with steroids and perioperative steroids were not found to be independent predictors of recurrence. Recurrence occurred in 2 of 34 (5.9%) patients with drain, and in 7 of 51 (13.7%) without (p=0.305). There were insufficient data to compare mortality and complications. Conclusions: Use of post-operative subdural drain did not significantly alter the cSDH recurrence rate.

Anti-N-methyl-D-aspartate receptor (NMDA-R) encephalitis is little known to pediatricians and likely underdiagnosed. The child's vital and cognitive prognosis is at stake. The use of immunomodulatory drugs, such as rituximab has led to spectacular results, but many questions remain about its mode of action in this type of pathology.We report the case of a 6-year-old girl with no medical history, admitted for status epilepticus preceded by behavior symptoms and sleep disorders. Gradually, the child became bedridden, mute, and animated by predominantly orofacial dyskinesia. Examinations were normal (cerebrospinal fluid [CSF] analysis, brain MRI). The diagnosis was established by the presence of NMDA-R antibodies in the CSF. After exclusion of a tumor-associated syndrome, treatment was started initially by intravenous immunoglobulins, then by plasma exchange, and finally rituximab. The patient was cured with rituximab despite an unusually early recovery of the B-cell pool.Anti-N-methyl-D-aspartate receptor (NMDA-R) encephalitis is a severe but potentially reversible neurologic disorder only recently described, even in childhood. It may be reversible without sequelae if diagnosed and treated early. The use of immunomodulatory therapy, such as rituximab seemingly improves the outcome. Immunological monitoring is needed to better understand its mechanism of action in autoimmune diseases of the nervous system in childhood.

Rituximab, a monoclonal antibody specifically targeting CD20, induces B cell depletion and is effective in the treatment of rheumatoid arthritis (RA). This study was undertaken to evaluate whether routine monitoring of lymphocyte subpopulations, especially T cells, may be useful in patients receiving rituximab for RA.We examined data on all RA patients receiving rituximab between July 2007 and November 2012 in our center. Peripheral blood CD3+, CD4+, CD8+, CD3-CD56+, and CD19+ lymphocyte counts before and during the first course of rituximab were measured by flow cytometry. The Mann-Whitney nonparametric test was used to compare lymphocyte subpopulation counts before and during treatment.Data on 52 patients were examined. Rituximab induced unexpected and substantial depletion of T cells, mainly CD4+ cells, in most patients. The CD4+ cell count decreased by a mean ± SD of 37 ± 33% as compared to baseline at week 12, reaching200 cells/μl in 3 patients. Importantly, lack of CD4+ cell depletion was associated with no clinical response. Therefore, the mechanism of action of rituximab may depend at least in part on T cells.Rituximab induces substantial T cell depletion, mainly of CD4+ cells, which is associated with the clinical response in RA. Routine monitoring of T cells may be useful in the clinical setting of RA.

Background: The evaluation of patients presenting with spinal metastatic disease is often challenging. The Tokuhashi scale intends to facilitate this process. We conducted this study to investigate its clinical utility in surgical-decision making in patients with spinal metastasis. Methods: The oncology database was used to allocate 285 patients with spinal metastasis between 2010 and 2015. The Tokuhashi scale components were determined from a chart review. Results: Based on the Tokuhashi scale, there was 69.1% in the non-operative/radiation group (group 1), 23.2% in the palliative/excisional surgical group (group2) and 7.7% in the surgical group (group 3). Using Kaplan-Meiers estimate, survival time was significantly different across the three groups with means 232.8±30.8, 352.3±49.2 and 568.3±206.1 days, respectively. A significantly higher proportion of patients (84.6%) were treated non-surgically in group 1, compared to 45.5% in group 3 (X2=19.5, PConclusions: This review illustrates the utility of the Tokuhashi scale in predicting survival. However, it does not address the new role of emerging different surgical strategies for the treatment of spinal metastasis and lacks information concerning spinal instability.

Background: The management of central cord syndrome (CCS) is controversial. There is a perception that CCS patients tend to improve without the need for surgical intervention. The purpose of this study was to compare the clinical improvements of patients with traumatic SCI, both with and without CCS. Methods: Nova Scotia Provincial Trauma Registry was retrospectively reviewed from 2005-2010. Improvement in the American Spinal Injury Association (ASIA) Impairment Scale (AIS) was determined after mean 5 months follow-up. Results: The study population comprised 96 cases with SCI, subdivided into cases with AIS grade A, non-CCS cases with AIS grades B-D and CCS cases. 88% of the non-CCS and 65% of the CCS patients underwent surgical decompression, with mean operative times being 71.6±137.8 and 102.9±144.6 post injury (p=0.45). The mean improvements in the mean ASIA motor scores for the three groups were 1.3±6.5 and 15.6±35.0 and 22.5±14.6 (p=0.004) respectively, with a statistically significant difference only between the CCS and AIS grade A groups (p2=8.0). Conclusions: This retrospective review investigates the natural history of CCS and explores the role of surgical intervention on optimizing patient outcome.

Background: The Spinal Instability Neoplastic Score (SINS) is used to assess mechanical instability based on radiographic and clinical factors. We conducted this study to evaluate the clinical utility of SINS in surgical decision-making in spinal metastasis and its association with metastatic epidural spinal cord compression (MESCC). Methods: We allocated 285 patients with spinal metastatic disease through a retrospective review. SINS was calculated using good-quality computed tomography. The degree of MESCC was assessed using 0 to 3 grading system. Results: Based on SINS, patients were categorized into stable (35.1%), potentially unstable (52.3%) and unstable (12.6%) groups. In the surgical intervention group, there was 69.5% treated with decompression and instrumented fusion, 17% with decompression alone, 8.5% with percutaneous vertebral augmentation and 5% with instrumented vertebral augmentation. A significantly higher proportion of patients with stable SINS (63.6%) were treated surgically without instrumentation (X2=10.6, P=0.005), whereas instrumentation was utilized in 87.5% of patients with unstable SINS. Grade 3 MESCC occurred in 65.5% of patients with unstable SINS, whereas 71.4% of patients with stable SINS had grade 0 MESCC (X2=42.1, PConclusions: SINS is associated with higher degrees of MESCC and plays an important role in surgical decision-making, facilitating assessment and recognition of spinal instability in need of urgent appropriate surgical interventions.

Background: This study aims to provide epidemiological data concerning spinal instability and patterns of metastatic invasion of the spine based on tumor histology. Methods: We allocated 285 patients with spinal metastatic disease through a retrospective review. SINS was calculated using good-quality computed tomography (CT) imaging studies. Spinal metastases were also grouped into intracompartmental, extracompartmental or multiple metastases. Results: Esophageal cancer was the least likely to be associated with instability with about 64% of cases being stable. The highest rate of instability scores was observed in breast carcinoma with 18% of cases graded as unstable. Renal cell carcinoma was associated with lytic spinal metastases whereas blastic metastases mostly occurred in prostate carcinoma (PConclusions: This study sheds light on the patterns of spinal metastatic disease and mechanical instability on the basis of tumor histology, utilizing standardized scoring systems. The utilization of such scoring systems allows for a standardized approach towards description and analysis of spinal metastasis facilitating clinical research in this avenue.

Current models for TCR/CD3 complex stoichiometry involve one or alternatively two TCR heterodimer(s) associated with two CD3 epsilon per complex. They mainly constructed on the basis of biochemical studies involving disruption of membrane complexes. The present study was undertaken to quantify the relative proportions of CD3 epsilon and TCR chains on alpha beta and gamma delta lymphocytes in nondenaturing conditions. Quantitative flow cytometry revealed that alpha beta and gamma delta PBL express on an average 1.56 and 1.52 more CD3 epsilon-chain than beta- and delta-chains, respectively. Accordingly, CD3 epsilon to TCR-alpha, TCR-beta, TCR-gamma, and TCR-delta ratios found on three polyclonal cell lines and on Jurkat cells were all very close to 1.50. These results clearly demonstrate that alpha beta as well as gamma delta T cells express approximately 1.50 more CD3 epsilon-chain than each of the TCR chains. They strongly suggest that alpha beta and gamma delta TCR/CD3 complexes involve two TCR heterodimers associated with three CD3 epsilon-chains (or a multiple of this combination). In addition, our results showed that gamma delta PBL expressed about 1.90 more TCR (-delta vs -beta) and CD3 epsilon-chains than alpha beta PBL. Furthermore, TCR-beta expression and CD3 epsilon expression were higher on CD4+ alpha beta PBL than on CD8+ alpha beta PBL, whereas TCR-delta expression and CD3 epsilon expression were both identical on CD8+ gamma delta PBL and on CD8- gamma delta PBL. These results demonstrate that CD8+ or CD8- gamma delta PBL, CD4+ alpha beta PBL and CD8+ alpha beta PBL express decreasing levels of the TCR/CD3 complex.

Introduction: Although alcohol use increases the risk of experiencing a traumatic brain injury (TBI), it remains unclear whether outcomes in alcohol-impaired patients are different from those of unimpaired patients. The objective of this study was to evaluate the effect of alcohol on length of stay (LOS) and mortality in patients with major TBI. Methods: Using data collected from the Nova Scotia Trauma Registry, we performed a retrospective analysis of all patients with major TBI (defined as having an abbreviated injury score (AIS) head ≥3) seen in Nova Scotia hospitals between 2002 and 2013. Patients were compared by blood alcohol concentration (BAC) at time of injury: negative (0-1.9 mmol/L), low (2-21 mmol/L), and moderate/high (≥22 mmol/L). A logistic regression model was constructed to test for outcomes and adjusted for the effects of age, gender, location, injury severity score (ISS), and BAC level. Results: In a twelve-year period, there were 4152 major TBI patients in Nova Scotia. Alcohol testing was performed in 43% of cases (80% male, mean age 44±20 years), with 48% having a positive BAC. Mean acute LOS was similar for all three BAC groups. Increasing age (odds ratio [OR]=1.01; pConclusion: Our findings suggest that low BAC levels are associated with increased mortality in major TBI patients. Further study is warranted to elucidate alcohol’s mechanism in TBI outcomes.

Introduction: Traumatic brain injury (TBI) is a leading cause of death and disability in Nova Scotia. TBI occurs in approximately 50% of major trauma seen annually in the province. The purpose of this study was to describe the characteristics and patterns of major TBI seen in Nova Scotia over a 12-year period. Methods: This was a retrospective case series. Data were obtained from the Nova Scotia Trauma Registry for all patients presenting with major TBI (abbreviated injury score [AIS] head ≥3) between 2002 and 2013. Injury rates were calculated on the basis of 100,000 population (all ages) using population estimates from Statistics Canada. Results: Overall, 4152 major TBI patients were seen in Nova Scotia hospitals during the study period. Mean age of TBI patients was 51±25 years; 73% were male. The majority of injuries were the result of blunt trauma (93%), with relatively few major TBIs resulting from penetrating trauma (7%). The most common mechanisms of injury were falls (44%) and motor vehicle crashes (27%). Analysis of census-based subpopulations of the province showed that injury rates varied significantly among counties (from 25 to 63 per 100,000 population). We observed an increase in the number of major TBI patients over twelve years. Conclusion: Our findings suggest significant regional variation in major TBI rates in Nova Scotia. There are ongoing needs for prevention and intervention efforts that focus on unintentional falls and motor vehicle crashes, especially in older adults. These results also suggest that geographically targeted efforts may be warranted.

To determine atrial natriuretic peptide (ANP) adaptation to simulated weightlessness, immunoreactive plasma (ir-NH2- and ir-COOH-terminals) and atrial (ir-COOH-terminal) ANP levels, atrial mRNA expression, immunoreactive cardiocyte ANP levels (ir-NH2- and ir-COOH-terminals), and ultrastructural observations of granules in atrial cardiocytes were assessed in male Wistar rats after a 9-day hindlimb suspension. Plasma ir-NH2- and ir-COOH-terminal ANP concentrations decreased by 17 (P < 0.05) and 37% (P < 0.05), respectively, in suspended rats. A concomitant ir-COOH-terminal ANP content reduction was also observed in left (31%; P < 0.01) and right atria (25%; P < 0.05). Atrial ANP mRNA expression was severely depleted in the right atrium and less so in the left atrium after 9 days of hindlimb suspension. Immunocytochemistry observations demonstrated lowered NH2- and COOH-terminal ANP immunoreactivities in left and right atria from suspended rats. A reduced number of storage granules (dense granules) in both atria was also noted on ultrastructural analysis. It was concluded that ANP biosynthesis, storage, and release were decreased after a 9-day hindlimb suspension.

Characterization and cloning of the AT(1) and AT(2) receptors would not have been possible without an assay that could detect and measure the density and affinity of these receptors. The most frequently used, if not the only, methodological approach used to investigate these receptors is the radioligand binding assay performed either in a test tube with tissue-membrane preparations or cultured cells, or on tissue sections (the latter revealed by autoradiography). This chapter will only deal with the test-tube radioligand binding assay. In this assay, a radiolabeled ligand (labeled with (125)I or (3)H, for example) is incubated with a membrane preparation or cells in presence of receptor subtype-specific antagonist or agonist. After reaching equilibrium, the receptor-bound tracer is separated from the free tracer by rapid filtration through glass fiber filters or by centrifugation. The amount (cpm) of bound tracer is then used to calculate the density and affinity of each receptor subtype. Alternatively, other experiments can be designed to derive kinetics of association and dissociation or saturation.

To evaluate the natriuretic effect of a nonhypotensive dose of felodipine, 11 healthy volunteers (age: 21-28 years) on a high-sodium diet received the drug or its vehicle in a double-blind, randomized, crossover study. Administered intravenously at a dose level of 7.5 micrograms/min for 30 minutes followed by 5 micrograms/min for 120 minutes, felodipine increased natriuresis (546 +/- 69 vs. 454 +/- 39 mumol/min, P < 0.001) and diuresis (8.9 +/- 0.6 vs. 7.5 +/- 0.5 mL/min), compared to its vehicle. Renal plasma flow tended to be augmented, but there was a significant reduction of renal vascular resistance (0.085 +/- 0.004 vs. 0.101 +/- 0.012 mm Hg/mL/min, P < 0.03). The glomerular filtration rate was slightly decreased and proximal sodium reabsorption was diminished with no measurable effect on distal function. Felodipine stimulated plasma renin activity, but produced no changes in plasma atrial natriuretic factor, cGMP, aldosterone, and atrial vasopressin levels. In conclusion, felodipine induced natriuresis and diuresis while reducing proximal tubular sodium reabsorption.

IL-4 and TNF-alpha increase endothelial cell adhesiveness for PBL by promoting the expression of adhesion molecules. We investigated the intracellular cAMP involvement in the increased endothelial cell adhesivity induced by IL-4 or TNF-alpha. We showed that both IL-4 and TNF-alpha increased intracellular cAMP in endothelial cells (EC). Furthermore, dibutyryl-cAMP and forskolin (which increased intracellular cAMP) increased basic EC adhesivity for PBL. The co-stimulation of EC with cAMP elevating agents and TNF-alpha, but not IL-4, resulted in an additive increase in EC adhesiveness. 2',5' dideoxyadenosine, an inhibitor of adenylate cyclase, decreased PBL adhesion to IL-4- but not TNF-alpha-treated EC. Similarly, HA1004, a protein kinase A inhibitor, totally reversed the IL-4 but not TNF-alpha effect on EC adhesiveness, whereas H7, a protein kinase C inhibitor, did not antagonise cytokine-enhanced EC adhesivity. These results indicate that IL-4, but not TNF-alpha, uses a cAMP-dependent pathway to increase PBL adhesion. Furthermore, we showed that cAMP elevation in EC did not induce vascular cell adhesion molecule 1, the only identified adhesion molecule induced by IL-4, indicating that a rise in cAMP in EC promotes an as yet unidentified adhesion pathway. Our results show that IL-4 increases EC adhesiveness for PBL through activation of protein kinase A by promoting an unidentified adhesion pathway.

Lymphopenia is a predictor of the efficacy and hematological toxicity of chemotherapy in various advanced cancers. There is little data about this relationship in colorectal cancer. In this retrospective study, the influence of pretreatment lymphopenia on hematological toxicity and the efficacy of chemotherapy was investigated in colorectal cancer patients. In total, 260 patients were included in the study. Correlations between pre-treatment lymphopenia (lymphocyte count

The ability of syncytiotrophoblast plasma membrane lipid and protein fractions (STPM lipids, STPM proteins), tested under a reconstituted form, to inhibit lymphocyte proliferation induced by PHA was investigated. The cytostatic activity of STPM proteins appeared greater than that of the STPM lipids. Furthermore, IL-2 production and IL-2 receptor expression by activated lymphocytes were markedly decreased in the presence of STPM proteins compared to the native membrane but remained unaffected in the presence of STPM lipids. Finally, the inhibition of lymphoproliferation could be maintained after removal of the protein fraction from lymphocytes prior to stimulation by PHA. The biological and immunological significance of these results is discussed.

The effects of non-steroidal anti-inflammatory drugs (NSAIDs) on the blood pressure and renal function of essential hypertensive patients depend on the specific type of NSAID and antihypertensive drug administered. Twelve patients with essential hypertension, aged 35 to 59 years, stabilized (blood pressure less than 140/90 mmHg) with captopril, received ketoprofen (100 mg bid for 7 days) or matching placebo in a randomized double-blind cross-over fashion. A 3-week wash-out period was included between treatment periods. Blood pressure on the first and last days of the placebo treatment period (137 +/- 7 (SD)/80 +/- 8 and 139 +/- 11/81 +/- 9 mmHg) was similar to respective values during ketoprofen therapy (136 +/- 10/79 +/- 7 and 143 +/- 10/81 +/- 9 mmHg). The mean differences in systolic and diastolic blood pressures, at the end of the treatment periods, between ketoprofen and placebo were 4 (95% confidence intervals -5, +13) and 0 (-8, +8) mmHg, respectively. Ketoprofen had no effect on 24-h urinary sodium excretion (160 +/- 33 and 147 +/- 39 mmol/24 h for ketoprofen and placebo, respectively). Ketoprofen was without effect on glomerular filtration rate, renal plasma flow and filtration fraction. In conclusion, our data suggest that ketoprofen is a safe choice when short-term treatment with a NSAID is indicated in an essential hypertensive patient treated with a converting enzyme inhibitor such as captopril.

Atrial natriuretic peptide is stored by atrial myocytes in secretory granules, known as atrial specific granules, and is released from these granules by exocytosis. We have isolated a group of atrial proteins by affinity chromatography that bind to atrial specific granules in a calcium-dependent manner. The two major proteins isolated (32.5 kd and 67 kd) are calcium-binding proteins and have been identified as annexins V and VI by immunoblotting with specific antisera. The calcium dependence of their binding to atrial specific granules has been characterized in vitro and indicates that this interaction takes place at micromolar levels of calcium. In addition, the group of proteins isolated includes another calcium-binding protein of 20 kd, as well as GTP-binding proteins of 22 to 26 kd. Membrane interactions during exocytosis are presumably mediated by the interaction of specific proteins with the granule membrane. The properties of the proteins described here, and their ability to bind to atrial specific granules in a calcium-dependent manner, make them likely candidates in the search for regulatory proteins mediating atrial natriuretic peptide secretion.

The exercise-induced increase in plasma atriopeptin (ANP) has been related to exercise intensity. The independent effect of duration on the ANP response to dynamic exercise remains incompletely documented. The purpose of this study was to describe the time course of plasma ANP concentration during a 90-min cycling exercise protocol and to examine this in light of concurrent variations in plasma arginine vasopressin (AVP), aldosterone (ALD), and catecholamine (norepinephrine and epinephrine) concentrations as well as plasma renin activity (PRA). Seven male and four female healthy college students (23 +/- 2 yr) completed a prolonged exercise protocol on a cycle ergometer at an intensity of 67% of maximal O2 uptake. Venous blood was sampled through an indwelling catheter at rest, after 15, 30, 45, 60, and 90 min of exercise, and after 30 min of passive upright recovery. Results (means +/- SE) indicate an increase in ANP from rest (22 +/- 2.6 pg/ml) at 15 min of exercise (45.3 +/- 7.4 pg/ml) with a further increase at 30 min (59.4 +/- 9.8 pg/ml) and a leveling-off thereafter until completion of the exercise protocol (51.7 +/- 10.7 pg/ml). In plasma ALD and PRA, a significant increase was found from rest (ALD, 21.4 +/- 6.4 ng/dl), PRA, 2.5 +/- 0.5 ng.ml-1.h-1 after 30 min of cycling, which continued to increase until completion of the exercise (ALD 46.6 +/- 8.7 ng/dl, PRA 9.5 +/- 0.9 ng.ml-1.h-1.(ABSTRACT TRUNCATED AT 250 WORDS)

An automated chamber was built to simulate environmental conditions encountered during field drying. Air temperature and relative humidity, wind speed, and radiation intensity were modified by an air conditioning unit, a variable speed fan, and infrared lamps, respectively. Eight trays were filled with a windrow section, placed in the chamber, and suspended from an electronic scale that continuously weighed the evaporated water. Weighing accuracy was within 0.3%. The chamber is designed to rapidly compare various hay windrow conditioning treatments. Coefficients of variation on the drying rate coefficient were 3% for individual windrows and 16% between windrows under constant drying conditions over a 48 h period of continuous drying.

A theoretical analysis of the effect of altitude on running performance is presented using a mathematical model we have recently described and validated (J. Appl. Physiol. 67: 453–465, 1989). This model relates the average power output available over a given running time for a given combination of anaerobic capacity, maximal aerobic power, and endurance capability. For short sprinting distances, the contribution of aerobic metabolism to the energy requirement is small and the speed sustained is high. The reduction of maximal aerobic power with altitude is, thus, negligible, whereas the reduction of aerodynamic resistance is beneficial. Accordingly the performance steadily increases with altitude (e.g., average speed for 100 m at Mexico City is 101.9% of the average speed at sea level). On the other hand, the reduction in maximal aerobic power with altitude is associated with a reduction in performance over middle and long distances (800 m to marathon). For 400 m an improvement in performance is observed up to an altitude of approximately 2,400–2,500 m (average speed approximately 101.4% of sea level speed). Beyond this altitude the reduction in air density cannot compensate for the reduction in maximal aerobic power, and the performance deteriorates. Tables of performances equivalent to the current world records for selected altitudes ranging from 0 to 4,000 m are proposed.

Intelligence in the asymmetric environment appears to lend itself to relying more heavily on information coming from human sources which may provide a wealth of opportunistic intelligence. This kind of information is increasingly available in very large quantities and various formats. The intelligence community has the challenge of ensuring that this collected information/knowledge, which is, by its very nature, mostly unstructured, can actually be "packaged" efficiently so that it can be readily and efficiently exploited for all of its intelligence value. After revisiting the intelligence process and paying particular attention to collation and analysis, the problem of collation is exposed and potential avenues of solutions presented.