The 2016 revision of the WHO Classification of Central Nervous System Tumours: retrospective application to a cohort of diffuse gliomas.

The classification of central nervous system tumours has more recently been shaped by a focus on molecular pathology rather than histopathology. We re-classified 82 glial tumours according to the molecular-genetic criteria of the 2016 revision of the World Health Organization (WHO) Classification of Tumours of the Central Nervous System. Initial diagnoses and grading were based on the morphological criteria of the 2007 WHO scheme. Because of the impression of an oligodendroglial component on initial histological assessment, each tumour was tested for co-deletion of chromosomes 1p and 19q and mutations of isocitrate dehydrogenase (IDH-1 and 2) genes. Additionally, expression of proteins encoded by alpha-thalassemia X-linked mental retardation (ATRX) and TP53 genes was assessed by immunohistochemistry. We found that all but two tumours could be assigned to a specific category in the 2016 revision. The most common change in diagnosis was from oligoastrocytoma to specifically astrocytoma or oligodendroglioma. Analysis of progression free survival (PFS) for WHO grade II and III tumours showed that the objective criteria of the 2016 revision separated diffuse gliomas into three distinct molecular categories: chromosome 1p/19q co-deleted/IDH mutant, intact 1p/19q/IDH mutant and IDH wild type. No significant difference in PFS was found when comparing IDH mutant grade II and III tumours suggesting that IDH status is more informative than tumour grade. The segregation into distinct molecular sub-types that is achieved by the 2016 revision provides an objective evidence base for managing patients with grade II and III diffuse gliomas based on prognosis.

Profiling an electrospray plume by laser-induced fluorescence and Fraunhofer diffraction combined to mass spectrometry: influence of size and composition of droplets on charge-state distributions of electrosprayed proteins.

We investigated how physico-chemical properties of charged droplets are affected by the electrospray process, using simultaneous in situ measurements by laser-induced fluorescence (LIF), Fraunhofer diffraction and mass spectrometry. For this purpose, we implemented a laser-induced-fluorescence profiling setup in conjunction with a fast, high-resolution particle sizing scheme on a modified Agilent Jet Stream electrospray source coupled to a single quadrupole mass analyser. The optical setup permits us to profile the solvent fractionation and the size of the droplets as they evaporate in an electrospray plume by measuring both the angular scattering pattern and emission spectra of a solvatochromic fluorescent dye. Mass spectra are recorded simultaneously. These mass spectrometry and optical spectroscopy investigations allow us to study the relation between the observed charge-state distributions of protein anions and physico-chemical properties of evaporating droplets in the spray plume. By mixing water with methanol, a refolding of cytochrome C is observed as the water percentage increases in the plume due to the preponderant evaporation of volatile methanol.

Reoperation for Recurrent Glioblastoma and Its Association With Survival Benefit.

BACKGROUND: Glioblastoma is the most common and aggressive primary brain tumor. Despite current treatment, recurrence is inevitable. There are no clear guidelines for treatment of recurrent glioblastoma. OBJECTIVE: To investigate factors at initial surgery predictive of reoperation, and the prognostic variables associated with survival, including reoperation for recurrence. METHODS: A retrospective cohort study was performed, including adult patients diagnosed with glioblastoma between January 2010 and December 2013. Student t test and Fisher exact test compared continuous and categorical variables between reoperation and nonreoperation groups. Univariable and Cox regression multivariable analysis was performed. RESULTS: In a cohort of 204 patients with de novo glioblastoma, 49 (24%) received reoperation at recurrence. The median overall survival in the reoperation group was 20.1 months compared with 9.0 months in the nonreoperation group (P = .001). Reoperation was associated with longer overall survival in our total population (hazard ratio, 0.646; 95% confidence interval, 0.543-0.922; P = .016) but subject to selection bias. Subgroup analyses excluding patients unlikely to be considered for reoperation suggested a much less significant effect of reoperation on survival, which warrants further study with larger cohorts. Factors at initial surgery predictive for reoperation were younger age, smaller tumor size, initial extent of resection ≥50%, shorter inpatient stay, and maximal initial adjuvant therapy. When unfavorable patient characteristics are excluded, reoperation is not an independent predictor of survival. CONCLUSION: Patients undergoing reoperation have favorable prognostic characteristics, which may be responsible for the survival difference observed. We recommend that a large clinical registry be developed to better aid consistent and homogenous data collection. ABBREVIATIONS: ECOG, Eastern Cooperative Oncology GroupEOR, extent of resectionIDH-1, isocitrate dehydrogenase 1IP, inpatientMGMT, O-methylguanine methyltransferaseOS, overall survivalPFS, progression-free survivalRMH, Royal Melbourne Hospital.

Basic vapor exposure for tuning the charge state distribution of proteins in negative electrospray ionization: elucidation of mechanisms by fluorescence spectroscopy.

Manipulation for simplifying or increasing the observed charge state distributions of proteins can be highly desirable in mass spectrometry experiments. In the present work, we implemented a vapor introduction technique to an Agilent Jet Stream ESI (Agilent Technologies, Santa Clara, CA, USA) source. An apparatus was designed to allow for the enrichment of the nitrogen sheath gas with basic vapors. An optical setup, using laser-induced fluorescence and a pH-chromic dye, permits the pH profiling of the droplets as they evaporate in the electrospray plume. Mechanisms of pH droplet modification and its effect on the protein charging phenomenon are elucidated. An important finding is that the enrichment with basic vapors of the nitrogen sheath gas, which surrounds the nebulizer spray, leads to an increase in the spray current. This is attributed to an increase in the electrical conductivity of water-amine enriched solvent at the tip exit. Here, the increased current results in a generation of additional electrolytically produced OH(-) ions and a corresponding increase in the pH at the tip exit. Along the electrospray plume, the pH of the droplets increases due to both droplet evaporation and exposure to basic vapors from the seeded sheath gas. The pH evolution in the ESI plume obtained using pure and basic seeded sheath gas was correlated with the evolution of the charge state distribution observed in mass spectra of proteins, in the negative ion mode. Taking advantage of the Agilent Jet Stream source geometry, similar protein charge state distributions and ion intensities obtained with basic initial solutions, can be obtained using native solution conditions by seeding the heated sheath gas with basic vapors.

Use of the evidence base in substance abuse treatment programs for American Indians and Alaska Natives: pursuing quality in the crucible of practice and policy.

BACKGROUND: A variety of forces are now shaping a passionate debate regarding the optimal approaches to improving the quality of substance abuse services for American Indian and Alaska Native communities. While there have been some highly successful efforts to meld the traditions of American Indian and Alaska Native tribes with that of 12-step approaches, some American Indian and Alaska Natives remain profoundly uncomfortable with the dominance of this Euro-American approach to substance abuse treatment in their communities. This longstanding tension has now been complicated by the emergence of a number of evidence-based treatments that, while holding promise for improving treatment for American Indian and Alaska Natives with substance use problems, may conflict with both American Indian and Alaska Native and 12-step healing traditions. DISCUSSION: We convened a panel of experts from American Indian and Alaska Native communities, substance abuse treatment programs serving these communities, and researchers to discuss and analyze these controversies in preparation for a national study of American Indian and Alaska Native substance abuse services. While the panel identified programs that are using evidence-based treatments, members still voiced concerns about the cultural appropriateness of many evidence-based treatments as well as the lack of guidance on how to adapt them for use with American Indians and Alaska Natives. The panel concluded that the efforts of federal and state policymakers to promote the use of evidence-based treatments are further complicating an already-contentious debate within American Indian and Alaska Native communities on how to provide effective substance abuse services. This external pressure to utilize evidence-based treatments is particularly problematic given American Indian and Alaska Native communities' concerns about protecting their sovereign status. SUMMARY: Broadening this conversation beyond its primary focus on the use of evidence-based treatments to other salient issues such as building the necessary research evidence (including incorporating American Indian and Alaska Native cultural values into clinical practice) and developing the human and infrastructural resources to support the use of this evidence may be far more effective for advancing efforts to improve substance abuse services for American Indian and Alaska Native communities.

Counselor incentives to improve client retention in an outpatient substance abuse aftercare program.

Pay for performance, the provision of financial incentives for favorable performance, is increasingly under study as an evidence-based practice. This study estimated the improvement in client retention from offering incentives to 11 substance abuse counselors providing outpatient aftercare treatment. During the incentive period, a counselor could earn a bonus of $100, in addition to his regular compensation, for each client who completed at least five aftercare sessions (the "milestone" which we considered the minimum adequate dose of the aftercare curriculum). We evaluated this and a similar, 12-session incentive using a logistic regression in which the retention "milestone" was the dependent variable and the proportion of time in the incentive condition was the independent variable. Among the 123 clients offered this aftercare program, their probability of completing at least 5 sessions was 59% with the incentive compared to 33% beforehand (odds ratio 4.1, P<.01). These findings suggest that counselor incentives are an effective strategy to improve client retention in substance abuse treatment.

Finger-length ratios in female monozygotic twins discordant for sexual orientation.

The second to fourth finger digit ratio (2D:4D ratio) is a sex-dimorphic characteristic in humans that may reflect relative levels of first trimester prenatal sex hormones. Low interdigital ratio has been associated with high levels of androgens. It has been reported in unrelated women that low 2D:4D ratio is associated with lesbian sexual orientation, but because of the nature of those samples, it was not possible to conclude whether lower ratio (and hypothetically, higher androgen levels) in lesbians are due to differences in genetics as opposed to differences in environment. To test the hypothesis that low 2D:4D in lesbians is due to differences in environment, interdigital ratio data were analyzed in a sample of female monozygotic (MZ) twins discordant for sexual orientation (1 twin was lesbian, the other was heterosexual; n = 7 pairs). A control group of female MZ twins concordant for sexual orientation (both twins were lesbian) was used as a comparison (n = 5 pairs). In the twins discordant for sexual orientation, the lesbian twins had significantly lower 2D:4D ratios on both the right and left hands than their heterosexual cotwins. There were no significant differences for either hand in the twins concordant for sexual orientation. Because MZ twins share virtually the same genes, differences in 2D:4D ratio suggest that low 2D:4D ratio is a result of differences in prenatal environment.