The significance of intra-abdominal pressure in neurosurgery and neurological diseases : a narrative review and a conceptual proposal

Intra-abdominal pressure (IAP) is a physiological parameter that has gained considerable attention during the last few decades. The incidence of complications arising from increased IAP, known as intra-abdominal hypertension (IAH) or abdominal compartment syndrome in critically ill patients, is high and its impact is significant. The effects of IAP in neurological conditions and during surgical procedures are largely unexplored. IAP also appears to be relevant during neurosurgical procedures (spine and brain) in the prone position, and in selected cases, IAH may affect cerebrospinal fluid drainage after a ventriculoperitoneal shunt operation. Furthermore, raised IAP is one of the contributors to intracranial hypertension in patients with morbid obesity. In traumatic brain injury, case reports described how abdominal decompression lowers intracerebral pressure. The anatomical substrate for transmission of the IAP to the brain and venous system of the spine is the extradural neural axis compartment; the first reports of this phenomenon can be found in anatomical studies of the sixteenth century. In this review, we summarize the available knowledge on how IAP impacts the cerebrospinal venous system and the jugular venous system via two pathways, and we discuss the implications for neurosurgical procedures as well as the relevance of IAH in neurological disorders

Coronary calcium mass scores measured by identical 64-slice MDCT scanners are comparable: a cardiac phantom study

To assess whether absolute mass scores are comparable or differ between identical 64-slice MDCT scanners of the same manufacturer and to compare absolute mass scores to the physical mass and between scan modes using a calcified phantom. A non-moving anthropomorphic phantom with nine calcifications of three sizes and three densities was scanned 30 times on three 64-slice MDCT scanners of manufacturer A and on three 64-slice MDCT scanners of manufacturer B in both sequential and spiral scan mode. The mean mass scores and mass score variabilities of seven calcifications were determined for all scanners; two non-detectable calcifications were omitted. It was analyzed whether identical scanners yielded similar or significantly different mass scores. Furthermore mass scores were compared to the physical mass and mass scores were compared between scan modes. The mass score calibration factor was determined for all scanners. Mass scores obtained on identical scanners were similar for almost all calcifications. Overall, mass score differences between the scanners were small ranging from 1.5 to 3.4% for the total mass scores, and most differences between scanners were observed for high density calcifications. Mass scores were significantly different from the physical mass for almost all calcifications and all scanners. In sequential mode the total physical mass (167.8 mg) was significantly overestimated (+2.3%) for 4 out of 6 scanners. In spiral mode a significant overestimation (+2.5%) was found for system B and a significant underestimation (−1.8%) for two scanners of system A. Mass scores were dependent on the scan mode, for manufacturer A scores were higher in sequential mode and for manufacturer B in spiral mode. For system A using spiral scan mode no differences were found between identical scanners, whereas a few differences were found using sequential mode. For system B the scan mode did not affect the number of different mass scores between identical scanners. Mass scores obtained in the same scan mode are comparable between identical 64-slice CT scanners and identical 64-slice CT scanners on different sites can be used in follow-up studies. Furthermore, for all systems significant differences were found between mass scores and the physical calcium mass; however, the differences were relatively small and consistent

Software development practices in academia: a case study comparison

Academic software development practices often differ from those of commercial development settings, yet only limited research has been conducted on assessing software development practises in academia. Here we present a case study of software development practices in four open-source scientific codes over a period of nine years, characterizing the evolution of their respective development teams, their scientific productivity, and the adoption (or discontinuation) of specific software engineering practises as the team size changes. We show that the transient nature of the development team results in the adoption of different development strategies. We relate measures of publication output to accumulated numbers of developers and find that for the projects considered the time-scale for returns on expended development effort is approximately three years. We discuss the implications of our findings for evaluating the performance of research software development, and in general any computationally oriented scientific project.Computational Horizons in Cancer (CHIC) project under EU FP7 grant agreement number 600841 (JG); CRESTA project under EU FP7 grant agreement number 287703 (DG,US); UK Engineering and Physical Sciences Research Council under grant numbers EP/I017909/1 (www.2020science.net, DG,JG,JMO) and EP/I034602/1 (US)

Airflow limitation increases lung cancer risk in smokers:the Lifelines cohort study

BACKGROUND: The relationship between smoking, airflow limitation and lung cancer occurrence is unclear. This study aims to evaluate the relationship between airflow limitation and lung cancer, and the effect modification by smoking status. METHODS: We included participants with spirometry data from Lifelines, a population-based cohort study from the Northern Netherlands. Airflow limitation was defined as FEV1/FVC ratio < 0.7. The presence of pathology-confirmed primary lung cancer during a median follow-up of 9.5 years was collected. The Cox regression model was used and hazard ratios (HR) with 95% confidence interval (95%CI) were reported. Adjusted confounders included age, sex, educational level, smoking, passive smoking, asthma status and asbestos exposure. The effect modification by smoking status was investigated by estimating the relative excess risk due to interaction (RERI) and the ratio of HRs with 95%CI. RESULTS: Out of 98,630 participants, 14,200 (14.4%) had airflow limitation. In participants with and without airflow limitation, lung cancer incidence was 0.8% and 0.2%, respectively. The adjusted HR between airflow limitation and lung cancer risk was 1.7 (1.4-2.3). The association between airflow limitation and lung cancer differed by smoking status [former smokers: 2.1 (1.4 -3.2), current smokers: 2.2 (1.5-3.2)] and never smokers [0.9 (0.4-2.1)]. The RERI and ratio of HRs was 2.1 (0.7-3.4) and 2.5 (1.0-6.5) for former smokers, and 4.6 (95%CI: 1.8-7.4) and 2.5 (95%CI: 1.0-6.3) for current smokers, respectively. CONCLUSIONS: Airflow limitation increases lung cancer risk and this association is modified by smoking status. IMPACT: Ever smokers with airflow limitation are an important target group for the prevention of lung cancer

Microarray amplification bias: loss of 30% differentially expressed genes due to long probe – poly(A)-tail distances

BACKGROUND: Laser microdissection microscopy has become a rising tool to assess gene expression profiles of pure cell populations. Given the low yield of RNA, a second round of amplification is usually mandatory to yield sufficient amplified-RNA for microarray approaches. Since amplification induces truncation of RNA molecules, we studied the impact of a second round of amplification on identification of differentially expressed genes in relation to the probe - poly(A)-tail distances. RESULTS: Disagreement was observed between gene expression profiles acquired after a second round of amplification compared to a single round. Thirty percent of the differentially expressed genes identified after one round of amplification were not detected after two rounds. These inconsistent genes have a significant longer probe - poly(A)-tail distance. qRT-PCR on unamplified RNA confirmed differential expression of genes with a probe - poly(A)-tail distance >500 nucleotides appearing only after one round of amplification. CONCLUSION: Our data demonstrate a marked loss of 30% of truly differentially expressed genes after a second round of amplification. Therefore, we strongly recommend improvement of amplification procedures and importance of microarray probe design to allow detection of all differentially expressed genes in case of limited amounts of RNA

Psychological interventions in asthma

Asthma is a multifactorial chronic respiratory disease characterised by recurrent episodes of airway obstruction. The current management of asthma focuses principally on pharmacological treatments, which have a strong evidence base underlying their use. However, in clinical practice, poor symptom control remains a common problem for patients with asthma. Living with asthma has been linked with psychological co-morbidity including anxiety, depression, panic attacks and behavioural factors such as poor adherence and suboptimal self-management. Psychological disorders have a higher-than-expected prevalence in patients with difficult-to-control asthma. As psychological considerations play an important role in the management of people with asthma, it is not surprising that many psychological therapies have been applied in the management of asthma. There are case reports which support their use as an adjunct to pharmacological therapy in selected individuals, and in some clinical trials, benefit is demonstrated, but the evidence is not consistent. When findings are quantitatively synthesised in meta-analyses, no firm conclusions are able to be drawn and no guidelines recommend psychological interventions. These inconsistencies in findings may in part be due to poor study design, the combining of results of studies using different interventions and the diversity of ways patient benefit is assessed. Despite this weak evidence base, the rationale for psychological therapies is plausible, and this therapeutic modality is appealing to both patients and their clinicians as an adjunct to conventional pharmacological treatments. What are urgently required are rigorous evaluations of psychological therapies in asthma, on a par to the quality of pharmaceutical trials. From this evidence base, we can then determine which interventions are beneficial for our patients with asthma management and more specifically which psychological therapy is best suited for each patient

Veliparib in Combination with Carboplatin and Etoposide in Patients with Treatment-Naive Extensive-Stage Small Cell Lung Cancer:A Phase 2 Randomized Study

Purpose: This study investigated the efficacy and safety of oral PARP inhibitor veliparib, plus carboplatin and etoposide in patients with treatment-naive, extensive-stage small cell lung cancer (ED-SCLC). Patients and Methods: Patients were randomized 1:1:1 to veliparib [240 mg twice daily (BID) for 14 days] plus chemotherapy followed by veliparib maintenance (400 mg BID; veliparib throughout), veliparib plus chemotherapy followed by placebo (veliparib combination only), or placebo plus chemotherapy followed by placebo (control). Patients received 4-6 cycles of combination therapy, then maintenance until unacceptable toxicity/progression. The primary endpoint was progression-free survival (PFS) with veliparib throughout versus control. Results: Overall (N = 181), PFS was improved with veliparib throughout versus control [hazard ratio (HR), 0.67; 80% confidence interval (CI), 0.50-0.88; P = 0.059]; median PFS was 5.8 and 5.6 months, respectively. There was a trend toward improved PFS with veliparib throughout versus control in SLFN11-positive patients (HR, 0.6; 80% CI, 0.36-0.97). Median overall survival (OS) was 10.1 versus 12.4 months in the veliparib throughout and control arms, respectively (HR, 1.43; 80% CI, 1.09-1.88). Grade 3/4 adverse events were experienced by 82%, 88%, and 68% of patients in the veliparib throughout, veliparib combination-only and control arms, most commonly hematologic. Conclusions: Veliparib plus platinum chemotherapy followed by veliparib maintenance demonstrated improved PFS as first-line treatment for ED-SCLC with an acceptable safety profile, but there was no corresponding benefit in OS. Further investigation is warranted to define the role of biomarkers in this setting