Survival implications of postoperative restricted diffusion in high-grade glioma and limitations of intraoperative MRI detection.

PURPOSE: Here we assess whether the volume of cerebral ischemia induced during glioma surgery may negatively impact survival independently of neurological function. We also evaluate the sensitivity of intraoperative MRI (iMRI) in detecting cerebral ischemia during surgery. METHODS: We retrospectively reviewed 361 cranial surgeries that used a 3 Tesla iMRI. 165 patients met all inclusion criteria and were included in the final analysis. Diffusion weighted imaging (DWI) obtained during iMRI was compared to postoperative DWI obtained within 7 days of the operation in cases where no further resection occurred after the iMRI. RESULTS: 42 of 165 patients (25%) showed at least some evidence of restricted diffusion on postoperative (poMRI). 37 of these 42 (88%) cases lacked evidence of restricted diffusion on iMRI, meaning iMRI had a false-negative rate of 88% and a sensitivity of 12% in assessing the extent of ischemic brain after surgery. In high-grade gliomas, the volume of restricted diffusion on poMRI was predictive of overall survival, independent of new functional deficits acquired during surgery (p = 0.011). CONCLUSION: This study presents the largest case series to date analyzing the sensitivity of iMRI in detecting surgical ischemia. In high-grade gliomas, increased volume of ischemia correlated with worsening median overall survival (OS) irrespective of postoperative neurologic deficits. Future work will focus on improving intraoperative detection of ischemia during the hyperacute phase when interventions such as blood pressure modulation or direct application of vasodilator agents may be effective.

Safety and efficacy of EsoFLIP dilation in patients with esophageal dysmotility: a systematic review.

Esophageal manometry is utilized for the evaluation and classification of esophageal motility disorders. EndoFlip has been introduced as an adjunctive test to evaluate esophagogastric junction (EGJ) distensibility. Treatment options for achalasia and EGJ outflow obstruction (EGJOO) include pneumatic dilation, myotomy, and botulinum toxin. Recently, a therapeutic 30 mm hydrostatic balloon dilator (EsoFLIP, Medtronic, Minneapolis, MN, USA) has been introduced, which uses impedance planimetry technology like EndoFlip. We performed a systematic review to evaluate the safety and efficacy of EsoFLIP in the management of esophageal motility disorders. A systematic literature search was performed with Medline, Embase, Web of science, and Cochrane library databases from inception to November 2022 to identify studies utilizing EsoFLIP for management of esophageal motility disorders. Our primary outcome was clinical success, and secondary outcomes were adverse events. Eight observational studies including 222 patients met inclusion criteria. Diagnoses included achalasia (158), EGJOO (48), post-reflux surgery dysphagia (8), and achalasia-like disorder (8). All studies used 30 mm maximum balloon dilation except one which used 25 mm. The clinical success rate was 68.7%. Follow-up duration ranged from 1 week to a mean of 5.7 months. Perforation or tear occurred in four patients. EsoFLIP is a new therapeutic option for the management of achalasia and EGJOO and appears to be effective and safe. Future comparative studies with other therapeutic modalities are needed to understand its role in the management of esophageal motility disorders.

Global liberalism, emerging illiberalism, and human rights, 1980 to 2018.

The international institutions established after 1945 enshrine and expand human rights norms. Recently, the global liberal order has been challenged by a variety of illiberal oppositions. We discuss how the trajectories of global liberalism and illiberal challenges may affect country human rights practices in both direct and diffuse ways. Hybrid panel regression models of human rights scores for 158 countries from 1980 to 2018 evaluate our arguments. We observe direct effects of global liberalism: countries linked to liberal organizations in world society have higher scores on measures of human rights practices. The growth of global liberalism also explains a great deal of within-country variation in human rights practices over time. However, recent illiberal challenges have the opposite effect. Countries linked to illiberal intergovernmental organizations are less respectful of human rights, and the global rise of illiberalism undermines human rights. We conclude with reflections on the importance of the global institutional and normative context for sustaining (and eroding) human rights.

Innovation in regulatory approaches for endocrine disrupting chemicals: The journey to risk assessment modernization in Canada.

Globally, regulatory authorities grapple with the challenge of assessing the hazards and risks to human and ecosystem health that may result from exposure to chemicals that disrupt the normal functioning of endocrine systems. Rapidly increasing number of chemicals in commerce, coupled with the reliance on traditional, costly animal experiments for hazard characterization - often with limited sensitivity to many important mechanisms of endocrine disruption -, presents ongoing challenges for chemical regulation. The consequence is a limited number of chemicals for which there is sufficient data to assess if there is endocrine toxicity and hence few chemicals with thorough hazard characterization. To address this challenge, regulatory assessment of endocrine disrupting chemicals (EDCs) is benefiting from a revolution in toxicology that focuses on New Approach Methodologies (NAMs) to more rapidly identify, prioritize, and assess the potential risks from exposure to chemicals using novel, more efficient, and more mechanistically driven methodologies and tools. Incorporated into Integrated Approaches to Testing and Assessment (IATA) and guided by conceptual frameworks such as Adverse Outcome Pathways (AOPs), emerging approaches focus initially on molecular interactions between the test chemical and potentially vulnerable biological systems instead of the need for animal toxicity data. These new toxicity testing methods can be complemented with in silico and computational toxicology approaches, including those that predict chemical kinetics. Coupled with exposure data, these will inform risk-based decision-making approaches. Canada is part of a global network collaborating on building confidence in the use of NAMs for regulatory assessment of EDCs. Herein, we review the current approaches to EDC regulation globally (mainly from the perspective of human health), and provide a perspective on how the advances for regulatory testing and assessment can be applied and discuss the promises and challenges faced in adopting these novel approaches to minimize risks due to EDC exposure in Canada, and our world.

Effects of endocrine disrupting chemicals on gonad development: Mechanistic insights from fish and mammals.

Over the past century, evidence has emerged that endocrine disrupting chemicals (EDCs) have an impact on reproductive health. An increased frequency of reproductive disorders has been observed worldwide in both wildlife and humans that is correlated with accidental exposures to EDCs and their increased production. Epidemiological and experimental studies have highlighted the consequences of early exposures and the existence of key windows of sensitivity during development. Such early in life exposures can have an immediate impact on gonadal and reproductive tract development, as well as on long-term reproductive health in both males and females. Traditionally, EDCs were thought to exert their effects by modifying the endocrine pathways controlling reproduction. Advances in knowledge of the mechanisms regulating sex determination, differentiation and gonadal development in fish and rodents have led to a better understanding of the molecular mechanisms underlying the effects of early exposure to EDCs on reproduction. In this manuscript, we review the key developmental stages sensitive to EDCs and the state of knowledge on the mechanisms by which model EDCs affect these processes, based on the roadmap of gonad development specific to fish and mammals.

Frontal fibrosing alopecia: survey of severity assessment methods in routine clinical practice and validation of the International Frontal Fibrosing Alopecia Cooperative Group measurement guidance.

BACKGROUND: The lack of validated and responsive outcome measures in the management of frontal fibrosing alopecia (FFA) significantly limits assessment of disease progression and treatment response over time. AIM: To understand how FFA extent and progression is currently assessed in UK specialist centres, to validate components of the International FFA Cooperative Group (IFFACG) statement on FFA assessment, and to identify pragmatic advice to improve FFA management in clinic. METHODS: Consultant dermatologists with a specialist interest in hair loss (n = 17) were invited to take part. Preferred FFA assessment methods were explored using questionnaires and clinical scenarios. Participants were asked to identify and mark the current hairline in 10 frontal and 10 temporal hairline images (Questionnaire 1), with assessment repeated 3 months later to assess intraindividual variability (Questionnaire 2) and 12 months later to test whether interindividual accuracy could be improved with simple instruction (Questionnaire 3). RESULTS: All 17 clinicians (100%) completed the questionnaire at each time interval. We identified a wide variation in assessment techniques used by our experts. Measurements were perceived as the most accurate method of assessing frontal recession whereas photography was preferred for temporal recession. Inter-rater reliability between clinicians measuring the frontal hairline scenarios indicated a moderate strength of agreement [intraclass coefficient (ICC) = 0.61; 95% CI 0.40-0.85], yet intrarater reliability was found to be poor with wide limits of agreement (-8.71 mm to 9.92 mm) on follow-up. Importantly, when clear guidance was provided on how the hairline should be identified (Questionnaire 3), inter-rater reliability improved significantly, with ICC = 0.70, suggesting moderate agreement (95% CI 0.51-0.89; P < 0.001). A similar pattern was seen with temporal hairline measurements, which again improved in accuracy with instruction. CONCLUSION: We found that accuracy of measurements in FFA can be improved with simple instruction and we have validated components of the IFFACG measurement recommendations.

The impact of signposting and group support pathways on a community-based physical activity intervention grounded in motivational interviewing.

BACKGROUND: Brief advice is recommended to increase physical activity (PA) within primary care. This study assessed change in PA levels and mental well-being after a motivational interviewing (MI) community-based PA intervention and the impact of signposting (SP) and social action (SA) (i.e. weekly group support) pathways. METHODS: Participants (n = 2084) took part in a community-based, primary care PA programme using MI techniques. Self-reported PA and mental well-being data were collected at baseline (following an initial 30-min MI appointment), 12 weeks, 6 months and 12 months. Participants were assigned based upon the surgery they attended to the SP or SA pathway. Multilevel models derived point estimates and 95% confidence intervals for outcomes at each time point and change scores. RESULTS: Participants increased PA and mental well-being at each follow-up time point through both participant pathways and with little difference between pathways. Retention was similar between pathways at 12 weeks, but the SP pathway retained more participants at 6 and 12 months. CONCLUSIONS: Both pathways produced similar improvements in PA and mental well-being; however, the addition of a control would have provided further insight as to the effectiveness. Due to lower resources yet similar effects, the SP pathway could be incorporated to support PA in primary care settings.

No Association Linking Short-Term Proton Pump Inhibitor Use to Dementia: Systematic Review and Meta-analysis of Observational Studies.

INTRODUCTION: Long-term use of proton pump inhibitors (PPIs) has been associated with a wide variety of potentially serious adverse effects including a possible increased risk of dementia. Studies evaluating this association have reached divergent conclusions. We aimed to evaluate this proposed association further and to assess the quality of the evidence in its support. METHODS: We searched MEDLINE, EMBASE, ISI Web of Science, and Cochrane databases for studies examining a link between PPI use and dementia, up to February 2019. Studies reporting summary results as hazard ratio (HR) or odds ratio (OR) were pooled using the DerSimonian and Laird random-effects model for meta-analyses. Methodological quality of individual observational studies was assessed using the Newcastle-Ottawa scale and the overall quality of evidence rated as per the GRADE approach. RESULTS: We identified and included 11 observational studies comprising 642,949 subjects; 64% were women. Most studies were short-term ranging from 5 to 10 years. There were 158,954 PPI users and 483,995 nonusers. For studies summarizing data as adjusted HR, pooled HR for all causes of dementia was 1.10 (0.88-1.37); for Alzheimer dementia only, it was 1.06 (0.72-1.55). For studies summarizing data as adjusted OR, pooled OR for all causes of dementia was 1.03 (0.84-1.25) and for Alzheimer dementia only 0.96 (0.82-1.11). Per Newcastle-Ottawa scale assessment, 10 studies were of high quality and 1 was of moderate quality. By applying GRADE methodology, quality of evidence for both outcomes was very low. DISCUSSION: We found no evidence to support the proposed association between PPI use and an increased risk of dementia. PPI use among patients who have a valid indication for it, should not be curtailed because of concerns about dementia risk.

Temporal lobe regions essential for preserved picture naming after left temporal epilepsy surgery.

OBJECTIVE: To define left temporal lobe regions where surgical resection produces a persistent postoperative decline in naming visual objects. METHODS: Pre- and postoperative brain magnetic resonance imaging data and picture naming (Boston Naming Test) scores were obtained prospectively from 59 people with drug-resistant left temporal lobe epilepsy. All patients had left hemisphere language dominance at baseline and underwent surgical resection or ablation in the left temporal lobe. Postoperative naming assessment occurred approximately 7 months after surgery. Surgical lesions were mapped to a standard template, and the relationship between presence or absence of a lesion and the degree of naming decline was tested at each template voxel while controlling for effects of overall lesion size. RESULTS: Patients declined by an average of 15% in their naming score, with wide variation across individuals. Decline was significantly related to damage in a cluster of voxels in the ventral temporal lobe, located mainly in the fusiform gyrus approximately 4-6 cm posterior to the temporal tip. Extent of damage to this region explained roughly 50% of the variance in outcome. Picture naming decline was not related to hippocampal or temporal pole damage. SIGNIFICANCE: The results provide the first statistical map relating lesion location in left temporal lobe epilepsy surgery to picture naming decline, and they support previous observations of transient naming deficits from electrical stimulation in the basal temporal cortex. The critical lesion is relatively posterior and could be avoided in many patients undergoing left temporal lobe surgery for intractable epilepsy.

Changes in description naming for common and proper nouns after left anterior temporal lobectomy.

Numerous studies have shown that surgical resection of the left anterior temporal lobe (ATL) is associated with a decline in object naming ability (Hermann et al., 1999). In contrast, few studies have examined the effects of left ATL surgery on auditory description naming (ADN) or category-specific naming. Compared with object naming, which loads heavily on visual recognition processes, ADN provides a more specific measure of concept retrieval. The present study examined ADN declines in a large group of patients who were tested before and after left ATL surgery, using a 2 × 2 × 2 factorial manipulation of uniqueness (common vs. proper nouns), taxonomic category (living vs. nonliving things), and time (pre- vs. postsurgery). Significant declines occurred across all categories but were substantially larger for proper living (PL) concepts, i.e., famous individuals. The disproportionate decline in PL noun naming relative to other conditions is consistent with the notion that the left ATL is specialized not only for retrieval of unique entity concepts, but also plays a role in processing social concepts and person-specific features.

Assessment of aeration control strategies for biofilm-based partial nitritation/anammox systems.

The objective of this work was to compare the nitrogen removal in mainstream, biofilm-based partial nitritation anammox (PN/A) systems employing (1) constant setpoint dissolved oxygen (DO) control, (2) intermittent aeration, and (3) ammonia-based aeration control (ABAC). A detailed water resource recovery facility (WRRF) model was used to study the dynamic performance of these aeration control strategies with respect to treatment performance and energy consumption. The results show that constant setpoint DO control cannot meet typical regulatory limits for total ammonia nitrogen (NHx-N). Intermittent aeration shows improvement but requires optimisation of the aeration cycle. ABAC shows the best treatment performance with the advantages of continuous operation and over 20% lower average energy consumption as compared to intermittent aeration.

Beyond geography: Cultural zones and global patterns of modern-method contraceptive use.

To increase understanding of global variation in contraceptive use, we classify countries into "cultural zones" based on religious traditions and geographical regions. Using data for 156 countries, we model modern contraceptive use rates as a function of cultural zones, geographic regions, economic development, women's education, and time. We find that cultural zones explain modern-method contraceptive use better than geographic regions alone, even when adjusting for economic development, women's education, and time. We argue that practitioners and researchers should make use of cultural zones as a tool for understanding cross-national variation in sexual and reproductive health outcomes.

Working to protect rights: Women's civil liberties in cross-cultural perspective.

Using data for a majority of the world's countries over a 25- to 55-year period, this paper analyzes cross-cultural heterogeneity in women's civil liberties independently of and relative to men. Civil liberties include the freedoms of discussion and movement, freedom from forced labor, property rights, and access to justice. Regression analyses show that women's civil liberties vary considerably across cultural zones defined by the intersection of religious traditions and geographical regions. These patterns persist even when controlling for factors such as democracy and development. Accounting for women's political representation and educational attainment often reduces but never eliminates these cross-cultural differences; the same is true for embeddedness in world society. In contrast, women's labor force participation all but erases negative cultural effects, and instrumental-variables analyses suggest that this factor is a causal determinant of women's civil liberties. Efforts to improve women's rights should therefore focus on overcoming cultural barriers to their workforce participation.

Time for a Changing of Guard: From Minimally Invasive Surgery to Endoscopic Drainage for Management of Pancreatic Walled-off Necrosis.

BACKGROUND AND AIMS: Endoscopic drainage (ED) with or without necrosectomy, and minimally invasive surgical necrosectomy (MISN) have been increasingly utilized for treatment of symptomatic sterile and infected pancreatic walled-off necrosis (WON). We conducted this systematic review to compare the safety of ED with MISN for management of WON. METHODS: We searched several databases from inception through November 9, 2017 to identify comparative studies evaluating the safety of ED versus MISN for management of WON. MISN could be performed using video-assisted retroperitoneal debridement or laparoscopy. We evaluated difference in mortality, major organ failure, adverse events, and length of hospital stay. RESULTS: Six studies (2 randomized controlled trials and 4 observational studies) with 641 patients (326 ED and 315 MISN) were included in this meta-analysis. Rates of mortality for ED and MISN were 8.5% and 14.2%, respectively. Pooled odds ratio (OR) with 95% confidence interval was 0.59 (0.35-0.98), I=0% in favor of ED. On subgroup analysis: no difference in mortality was seen based on randomized controlled trials [OR, 0.65 (0.08-5.11)], while ED had improved survival in observational studies [OR, 0.49 (0.27-0.89)]. Development of new major organ failure rates after interventions were 12% and 54% for ED and MISN, respectively. Pooled OR was 0.12 (0.06-0.31), I=25% in favor of ED. For adverse events, pooled OR was 0.25 (0.10-0.67), I=70% in favor of ED. There was no difference in risk of bleeding [OR, 0.68 (0.44-1.05)], while ED was associated with a significantly lower rate of pancreatic fistula formation [OR, 0.20 (0.11-0.37)], I=0%. Length of stay was also lower with ED, pooled mean difference was -21.07 (-36.97 to -5.18) days. CONCLUSIONS: When expertise is available, ED is the preferred invasive management strategy over MISN for management of WON as it is associated with lower mortality, risk of major organ failure, adverse events, and length of hospital stay.

Surpassing Single Line Width Active Tuning with Photochromic Molecules Coupled to Plasmonic Nanoantennas.

Active plasmonic nanostructures with tunable resonances promise to enable smart materials with multiple functionalities, on-chip spectral-based imaging and low-power optoelectronic devices. A variety of tunable materials have been integrated with plasmonic structures, however, the tuning range in the visible regime has been limited to less than the line width of the resonance resulting in small on/off ratios. Here we demonstrate dynamic tuning of plasmon resonances up to 71 nm through multiple cycles by incorporating photochromic molecules into plasmonic nanopatch antennas. Exposure to ultraviolet (UV) light switches the molecules into a photoactive state enabling dynamic control with on/off ratios up to 9.2 dB and a tuning figure of merit up to 1.43, defined as the ratio between the spectral shift and the initial line width of the plasmonic resonance. Moreover, the physical mechanisms underlying the large spectral shifts are elucidated by studying over 40 individual nanoantennas with fundamental resonances from 550 to 720 nm revealing good agreement with finite-element simulations.

Wealth and health revisited: Economic growth and wellbeing in developing countries, 1970 to 2015.

Is wealthier always healthier, or are the health effects of economic growth trivial, irregular, or perhaps even detrimental? Using data for up to 134 developing countries between 1970 and 2015, this article revisits the effect of economic growth on health, focusing on infant mortality, life expectancy, and caloric consumption. The analysis enlarges the geographical and temporal scope of previous samples and attempts to isolate the causal effects of growth using two-stage models with instrumental variables. Results show that five-year economic growth rates improve all three health outcomes, even after controlling for other important determinants and accounting for the possibility of reverse causality. Growth effects are largest for infant mortality rates. Nevertheless, there are diminishing returns to economic growth as a function of economic development: as countries become more affluent, the benefits of growth for health diminish.

Spatial discrimination of glioblastoma and treatment effect with histologically-validated perfusion and diffusion magnetic resonance imaging metrics.

The goal of this study is to spatially discriminate tumor from treatment effect (TE), within the contrast-enhancing lesion, for brain tumor patients at all stages of treatment. To this end, the diagnostic accuracy of MRI-derived diffusion and perfusion parameters to distinguish pure TE from pure glioblastoma (GBM) was determined utilizing spatially-correlated biopsy samples. From July 2010 through June 2015, brain tumor patients who underwent pre-operative DWI and DSC-MRI and stereotactic image-guided biopsy were considered for inclusion in this IRB-approved study. MRI-derived parameter maps included apparent diffusion coefficient (ADC), normalized cerebral blood flow (nCBF), normalized and standardized relative cerebral blood volume (nRCBV, sRCBV), peak signal-height (PSR) and percent signal-recovery (PSR). These were co-registered to the Stealth MRI and median values extracted from the spatially-matched biopsy regions. A ROC analysis accounting for multiple subject samples was performed, and the optimal threshold for distinguishing TE from GBM determined for each parameter. Histopathologic diagnosis of pure TE (n = 10) or pure GBM (n = 34) was confirmed in tissue samples from 15 consecutive subjects with analyzable data. Perfusion thresholds of sRCBV (3575; SN/SP% = 79.4/90.0), nRCBV (1.13; SN/SP% = 82.1/90.0), and nCBF (1.05; SN/SP% = 79.4/80.0) distinguished TE from GBM (P < 0.05), whereas ADC, PSR, and PH could not (P > 0.05). The thresholds for CBF and CBV can be applied to lesions with any admixture of tumor or treatment effect, enabling the identification of true tumor burden within enhancing lesions. This approach overcomes current limitations of averaging values from both tumor and TE for quantitative assessments.

Meta-analysis of the performance of ultrathin vs. standard colonoscopes.

Background and study aims Colonoscopy should reliably intubate the cecum with minimal patient discomfort and without complications. Use of thinner endoscopes to overcome pain during the procedure has shown promise. However, the use of thinner scopes could lead to excess looping and difficulty with therapeutic procedures. The aim of this meta-analysis was to analyze the performance of ultrathin colonoscopes (UTC) and standard colonoscopes for routine colonoscopy. Patients and methods We searched several electronic databases for all randomized controlled trials and nonrandomized (prospective) studies that compared the efficacies of UTC (diameter ≤ 9.8 mm) and standard colonoscopes. We used fixed effect or random effects models to compare cecal intubation rate, cecal intubation time, pain score, and polyp and adenoma detection rates using standard mean differences (SMD) or odds ratios (OR) with 95 % confidence intervals (CI). Results Seven studies (2191 patients) met the inclusion criteria. There was no significant heterogeneity among studies except for pain scores. The cecal intubation rate was higher with UTC (OR 2.30; 95 %CI 1.31 to 4.03). There was no difference in the cecal intubation time between UTC and standard colonoscopes. Pain scores were significantly lower with UTC than with standard colonoscopes (SMD - 0.59, 95 %CI - 0.93 to - 0.25). Polyp and adenoma detection rates were similar for both types of colonoscope. Conclusion Use of UTC appears to improve the cecal intubation rate and reduce abdominal pain but does not affect polyp detection. Future trials are needed to evaluate the therapeutic performance of UTC vs. standard colonoscopes.

Reduced prevalence of impaired awareness of hypoglycemia in a population-based clinic sample of youth with type 1 diabetes.

BACKGROUND: Impaired awareness of hypoglycemia (IAH) is associated with an increased risk for severe hypoglycemia (SH). However, reduced rates of SH raise the question as to whether there has been a reduction in IAH. The aim of this study was to determine the change in prevalence of IAH in a population-based cohort of adolescents with Type 1 diabetes (T1D). METHODS: Children older than 12 years with T1D documented their responses to hypoglycemia based on the modified Clarke questionnaire. The prevalence of IAH was also analyzed in a similar population-based cohort using the same questionnaire in 2002. The clinical details of the participants and the number of SH events in the preceding year were determined from the Western Australian diabetes database. RESULTS: The questionnaire was administered to 413 children in 2002 and to 444 children in 2015 with similar baseline characteristics. The prevalence of IAH was 33% in 2002 and 21% in 2015 (P < .001). A lower HbA1c, younger age at diagnosis and longer duration of diabetes correlated with IAH in 2002 but not in 2015. There was a significant decline in the rates of SH in 2015 compared with 2002 (P < .001) despite a reduced HbA1c in 2015. IAH increased the risk of SH in both cohorts (52 vs 16 events/100 patient years in 2002 and 8 vs 2 events/100 patient years in 2015). CONCLUSIONS: Although IAH has reduced, IAH is still prevalent in a substantial minority of adolescents and continues to be associated with an increased risk of SH.