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Many patients with SARS-CoV-2 infection develop neurological signs and symptoms; although, to date, little evidence exists that primary infection of the brain is a significant contributing factor. We present the clinical, neuropathological and molecular findings of 41 consecutive patients with SARS-CoV-2 infections who died and underwent autopsy in our medical centre. The mean age was 74 years (38–97 years), 27 patients (66%) were male and 34 (83%) were of Hispanic/Latinx ethnicity. Twenty-four patients (59%) were admitted to the intensive care unit. Hospital-associated complications were common, including eight patients (20%) with deep vein thrombosis/pulmonary embolism, seven (17%) with acute kidney injury requiring dialysis and 10 (24%) with positive blood cultures during admission. Eight (20%) patients died within 24 h of hospital admission, while 11 (27%) died more than 4 weeks after hospital admission. Neuropathological examination of 20–30 areas from each brain revealed hypoxic/ischaemic changes in all brains, both global and focal; large and small infarcts, many of which appeared haemorrhagic; and microglial activation with microglial nodules accompanied by neuronophagia, most prominently in the brainstem. We observed sparse T lymphocyte accumulation in either perivascular regions or in the brain parenchyma. Many brains contained atherosclerosis of large arteries and arteriolosclerosis, although none showed evidence of vasculitis. Eighteen patients (44%) exhibited pathologies of neurodegenerative diseases, which was not unexpected given the age range of our patients. We examined multiple fresh frozen and fixed tissues from 28 brains for the presence of viral RNA and protein, using quantitative reverse-transcriptase PCR, RNAscope® and immunocytochemistry with primers, probes and antibodies directed against the spike and nucleocapsid regions. The PCR analysis revealed low to very low, but detectable, viral RNA levels in the majority of brains, although they were far lower than those in the nasal epithelia. RNAscope® and immunocytochemistry failed to detect viral RNA or protein in brains. Our findings indicate that the levels of detectable virus in coronavirus disease 2019 brains are very low and do not correlate with the histopathological alterations. These findings suggest that microglial activation, microglial nodules and neuronophagia, observed in the majority of brains, do not result from direct viral infection of brain parenchyma, but more likely from systemic inflammation, perhaps with synergistic contribution from hypoxia/ischaemia. Further studies are needed to define whether these pathologies, if present in patients who survive coronavirus disease 2019, might contribute to chronic neurological problems.

Introduction: Unexplained regional variation exists in tissue plasminogen activator (tPA) treatment for stroke. Whether regional differences in stroke preparedness (stroke knowledge and intent to call 911) exist and contribute to tPA administration is unknown. We therefore sought to determine the contribution of stroke preparedness to regional variation in stroke treatment, as an association might support region-specific stroke preparedness interventions. Methods: We performed a retrospective ecological cross-sectional study measuring the association of regional stroke preparedness and regional tPA administration. We used Medicare data to determine the percentage of tPA-treated hospitalized stroke patients in 2007, 2009, & 2011, adjusting for the number of stroke hospitalizations in each hospital service area (HSA) (primary outcome). We determined stroke preparedness from Behavior Risk Factor Surveillance System survey questions assessing stroke symptom knowledge (score range 0-6) and intent to call 911 (score range 0-1) (exposure of interest). The association between regional preparedness and tPA treatment was assessed using multiple linear regression, adjusting for regional characteristics (demographic factors, the presence of EMS bypass, number of primary stroke centers, and hospital stroke volume). Results: There were 1738 HSAs. The adjusted percentage of stroke patients receiving tPA ranged from 1.37% (MIN) to 11.29% (MAX). Across HSAs, a median (IQR) of 86% (81%-90%) of responses to a witnessed stroke indicated intent to call 911 and a median (IQR) of 4.42 (4.24-4.59) out of 6 stroke symptoms were correctly recognized. Every 1% increase in accuracy in the question assessing intent to call 911 was associated with a 0.44% increase in adjusted tPA rate (p=0.049). Accurate stroke symptom recognition was not significantly associated with adjusted tPA rates across regions (p=0.05). Conclusions: Overall, there was little regional variation in intent to call 911 and stroke symptom recognition. Intent to activate EMS in response to a witnessed stroke is likely a modest contributor to regional variation in tPA treatment.

ObjectiveTo describe geographic variation in neurologist density, neurologic conditions, and neurologist involvement in neurologic care.MethodsWe used 20% 2015 Medicare data to summarize variation by Hospital Referral Region (HRR). Neurologic care was defined as office-based evaluation/management visits with a primary diagnosis of a neurologic condition.ResultsMean density of neurologists varied nearly 4-fold from the lowest to the highest density quintile (9.7 [95% confidence interval (CI) 9.2–10.2] vs 43.1 [95% CI 37.6–48.5] per 100,000 Medicare beneficiaries). The mean prevalence of patients with neurologic conditions did not substantially differ across neurologist density quintile regions (293 vs 311 per 1,000 beneficiaries in the lowest vs highest quintiles, respectively). Of patients with a neurologic condition, 23.5% were seen by a neurologist, ranging from 20.6% in the lowest quintile regions to 27.0% in the highest quintile regions (6.4% absolute difference). Most of the difference comprised dementia, pain, and stroke conditions seen by neurologists. In contrast, very little of the difference comprised Parkinson disease and multiple sclerosis, both of which had a very high proportion (>80%) of neurologist involvement even in the lowest quintile regions.ConclusionsThe supply of neurologists varies substantially by region, but the prevalence of neurologic conditions does not. As neurologist supply increases, access to neurologist care for certain neurologic conditions (dementia, pain, and stroke) increases much more than for others (Parkinson disease and multiple sclerosis). These data provide insight for policy makers when considering strategies in matching the demand for neurologic care with the appropriate supply of neurologists.

Drosophila melanogaster olfactory neurons have long been thought to express only one chemosensory receptor gene family. There are two main olfactory receptor gene families in Drosophila, the Odorant Receptors (ORs) and the Ionotropic Receptors (IRs). The dozens of odorant binding receptors in each family require at least one co-receptor gene in order to function: Orco for ORs, and Ir25a, Ir8a, and Ir76b for IRs. Using a new genetic knock-in strategy, we targeted the four co-receptors representing the main chemosensory families in Drosophila (Orco, Ir8a, Ir76b, Ir25a). Co-receptor knock-in expression patterns were verified as accurate representations of endogenous expression. We find extensive overlap in expression among the different co-receptors. As defined by innervation into antennal lobe glomeruli, Ir25a is broadly expressed in 88% of all olfactory sensory neuron classes and is co-expressed in 82% of Orco+ neuron classes, including all neuron classes in the maxillary palp. Orco, Ir8a, and Ir76b expression patterns are also more expansive than previously assumed. Single sensillum recordings from Orco-expressing Ir25a mutant antennal and palpal neurons identify changes in olfactory responses. These results suggest co-expression of chemosensory receptors is common in olfactory neurons. Together, our data present the first comprehensive map of chemosensory co-receptor expression and reveal their unexpected widespread co-expression in the fly olfactory system.

An efficient one-flask cascade method for synthesis of the multi-substituted 1,2,4-triazoles via chlorotrimethylsilane as a promoter was developed. Firstly, nitrilimines were transformed to hydrazonamides as intermediate in high yield by treatment with commercially available hexamethyldisilazane. Subsequently, the mixture was added with corresponding acyl chloride and heated in the presence of pyridine to give the corresponding multi-substituted 1,2,4-triazoles via chlorotrimethylsilane promoted heterocyclization reaction. The utility of method was demonstrated to synthesize CB1 ligands including Rimonabant analogue 4c and LH-21 3 for modeling study. All synthesized compounds were subjected to the cAMP functional assay of CB1/CB2 receptor. Especially, compound 4g enhanced the reversal of cAMP reduction by CP59440 than LH-21 and Rimonabant analogue in CHO-hCB1 cells. In addition, the docking results showed compound 4g fits the best position with CB1 receptor. However, the ability to penetrate brain-blood barrier of compound 4g is similar with Rimonabant in MDCK-mdr1 permeability assay, which might cause CNS side effect. This study still provides the basis for further development of a potent and specific CB1 antagonist.

Perianal fistulizing complications (PFCs) develop in 15% to 30% of patients with Crohn disease (CD), are difficult to treat, worsen quality of life, increase cost of care, and commonly recur. Evidence-based strategies to prevent PFCs are lacking.To investigate the effectiveness of medical therapy for reducing risk of PFCs among young people with CD and to test the hypothesis that steroid-sparing therapy (SST) use would be associated with reduced risk of PFC development.In this comparative effectiveness analysis of commercial administrative claims from January 1, 2001, through June 30, 2016, patients who did or did not initiate SST were matched via propensity score to adjust for all available confounders. Using Optum's Clinformatics Data Mart, a deidentified database of US commercial administrative claims, all patients aged 5 to 24 years with CD (January 1, 2001, through June 30, 2016) were identified. The index date was the CD diagnosis date. Patients with PFCs or SST use at or before CD diagnosis were excluded. The dates of analysis were October 2017 to February 2020.The primary exposure of interest was SST initiation, including immunomodulators and/or anti-tumor necrosis factor α (anti-TNFα) medications, initiated before either PFC development or the end of the study period.The primary outcome was PFC development. Propensity score matching was used to balance baseline characteristics. Cox proportional hazards multivariable regression analyses were used to estimate hazard ratios (HRs) with 95% CIs for PFC development.Among 2214 young people with CD without PFCs identified, the mean (SD) age at CD diagnosis was 17.0 (4.5) years, and 1151 (52.0%) were male. Among the cohort, 1242 patients (56.1%) initiated SST before PFC development or the end of 24-month follow-up. After propensity score matching, 972 patients remained in each treatment group. Overall, 384 of 1944 (19.8%) developed PFCs within 2 years of the index date. The use of SST was associated with a 59% decreased risk of PFC development (hazard ratio [HR], 0.41; 95% CI, 0.33-0.52; P .001) in 2 years compared with no SST use. Among those who developed PFCs, 55% fewer SST users underwent ostomy than SST nonusers. The use of immunomodulators alone, anti-TNFα alone, and combination therapy was associated with 52% (HR, 0.48; 95% CI, 0.37-0.62; P .001), 47% (HR, 0.53; 95% CI, 0.36-0.78; P = .001), and 83% (HR, 0.17; 95% CI, 0.09-0.30; P .001) reductions in the risk of 2-year PFC development, respectively, compared with no SST use.In this study, PFC development was common among young patients with CD. The use of SST was lower than expected. Compared with no SST, patients who initiated SST were 59% less likely to develop PFCs and fewer underwent ostomy. These results indicate that PFCs may be preventable and emphasize the importance of considering SST for all patients with CD.

OBJECTIVE: To determine the association of a neurologist visit with health care use and cost outcomes for patients with incident epilepsy. METHODS: Using health care claims data for individuals insured by United Healthcare from 2001 to 2016, we identified patients with incident epilepsy. The population was defined by an epilepsy/convulsion diagnosis code (ICD codes 345.xx/780.3x, G40.xx/R56.xx), an antiepileptic prescription filled within the succeeding 2 years, and neither criterion met in the 2 preceding years. Cases were defined as patients who had a neurologist encounter for epilepsy within 1 year after an incident diagnosis; a control cohort was constructed with propensity score matching. Primary outcomes were emergency room (ER) visits and hospitalizations for epilepsy. Secondary outcomes included measures of cost (epilepsy related, not epilepsy related, and antiepileptic drugs) and care escalation (including EEG evaluation and epilepsy surgery). RESULTS: After participant identification and propensity score matching, there were 3,400 cases and 3,400 controls. Epilepsy-related ER visits were more likely for cases than controls (year 1: 5.9% vs 2.3%, p < 0.001), as were hospitalizations (year 1: 2.1% vs 0.7%, p < 0.001). Total medical costs for epilepsy care, nonepilepsy care, and antiepileptic drugs were greater for cases (p ≤ 0.001). EEG evaluation and epilepsy surgery occurred more commonly for cases (p ≤ 0.001). CONCLUSIONS: Patients with epilepsy who visited a neurologist had greater subsequent health care use, medical costs, and care escalation than controls. This comparison using administrative claims is plausibly confounded by case disease severity, as suggested by higher nonepilepsy care costs. Linking patient-centered outcomes to claims data may provide the clinical resolution to assess care value within a heterogeneous population.

Background/objective Advance care planning (ACP) is associated with improved patient and caregiver outcomes, but is underutilized. To encourage ACP, the Centers for Medicare & Medicaid Services implemented specific ACP visit reimbursement codes in 2016. To better understand the utilization of these ACP reimbursement codes, we explored regional variation in billed ACP visits. Design We performed a retrospective cross-sectional analysis using a randomly sampled 5% cohort of Medicare fee-for-service (FFS) beneficiaries' claims files from 2017. Region was defined by hospital referral region. Setting National Medicare FFS. Participants A total of 1.3 million Medicare beneficiaries aged 65 years and older. Measurement Receipt of billed ACP service, identified through Current Procedural Terminology code 99497 or 99498. Proportion of beneficiaries who received billed ACP service(s) by region was calculated. We fit a multilevel logistic regression model with a random regional intercept to determine the variation in billed ACP visits attributable to the region after accounting for patient (demographics, comorbidities, and medical care utilization) and regional factors (hospital size, emergency department visits, hospice utilization, and costs). Results The study population included about 1.3 million beneficiaries, of which 32,137 (2.4%) had at least one billed ACP visit in 2017. There was substantial regional variation in the percentage of beneficiaries with billed ACP visits: lowest quintile region, less than 0.83%; subsequent regions, less than 1.6%, less than 2.4%, less than 3.3% to less than 8.4% in the highest quintile regions. A total of 15.4% of the variance in whether an older adult had a billed ACP visit was explained by the region. Although numerous regional factors were associated with billed ACP visits, none were strong predictors. Conclusion In 2017, we found wide regional variation in the use of billed ACP visits, although use overall was low in all regions. Increasing the understanding of the drivers and the effects of billed ACP visits could inform strategies for increasing ACP.

Multiple sclerosis (MS) is a chronic autoimmune disease of the CNS that is characterized by demyelination, axonal loss, gliosis, and inflammation. The murine model of MS is the experimental autoimmune encephalopathy (EAE) induced by immunization of mice with myelin oligodendrocyte glycoprotein (MOG)35–55. Ig-like transcript 3 (ILT3) is an inhibitory cell surface receptor expressed by tolerogenic human dendritic cells. In this study, we show that the recombinant human ILT3.Fc protein binds to murine immune cells and inhibits the release of proinflammatory cytokines that cause the neuroinflammatory process that result in paralysis. Administration of ILT3.Fc prevents the rapid evolution of the disease in C57BL/6 mice and is associated with a profound reduction of proliferation of MOG35–55–specific Th1 and Th17 cells. Inhibition of IFN-γ and IL-17A in mice treated with ILT3.Fc is associated with delayed time of onset of the disease and its evolution to a peak clinical score. Neuropathological analysis shows a reduction in inflammatory infiltrates and demyelinated areas in the brains and spinal cords of treated mice. These results indicate that inhibition of Th1 and Th17 development provides effective suppression of EAE and suggests the feasibility of a clinical approach based on the use of ILT3.Fc for treatment of MS. Furthermore, our results open the way to further studies on the effect of the human ILT3.Fc protein in murine experimental models of autoimmunity and cancer.

The impact of peroxide surface treatment on the resistive switching characteristics of zinc peroxide (ZnO2)-based programmable metallization cell (PMC) devices is investigated. The peroxide treatment results in a ZnO hexagonal to ZnO2 cubic phase transformation; however, an excessive treatment results in crystalline decomposition. The chemically synthesized ZnO2 promotes the occurrence of switching behavior in Cu/ZnO2/ZnO/ITO with much lower operation current as compared to the Cu/ZnO/ITO (control device). However, the switching stability degrades as performing the peroxide treatment for a longer time. We suggest that the microstructure of the ZnO2 is responsible for this degradation behavior and fine tuning on ZnO2 properties, which is necessary to achieve proper switching characteristics in ZnO2-based PMC devices.

Background: Hepatitis C virus (HCV) infection has a high persistence rate in patients. Although immune cells play a central role in determining the outcomes of HCV infection, the liver is crucial in controlling HCV activity from acute to chronic stages. This investigation grew HCV from a long-term cell culture, and provided an experimental model for studies on HCV persistence in hepatocytes. Methods: Huh7.5 cells implanted with the NS3/4 protease-based secreted alkaline phosphatase (SEAP) reporter were infected with JFH-1 HCV (moiety of infection = 0.01) and incubated for over 130 days. Results: The viral activity was obtained by sampling supernatant continuously for SEAP activity measurement. Combined with extracellular and intracellular HCV-RNAs and viral infectivity assays, the experimental results exhibited in vitro viral dynamics resembling the patients' viremia pattern from acute to chronic infections. The HCV in acute infection comprised exponential accumulation (week 1), plateau (week 2), declining production (weeks 3–4) and silencing (weeks 5–14) phases, and were then reactivated at the onset of chronic infection (after week 15). The HCV-infected cells grew more slowly than the mock controls, and exhibited a prominent decrease of cell growth rate and increase of early apoptosis in the declining-to-silencing phase transition, suggesting that fitness selection might occur as the infected cells moved across the boundary of active to occult viral activity. Conclusion: Cultivated HCV in the highly sensitive NS3/4-based SEAP reporter cells could establish persistence, which might mimic the viral dynamics from acute to chronic infections in hepatitis C patients. Keywords: Acute and chronic infections, Apoptosis, Hepatitis C virus, Long-term culture, Secreted alkaline phosphatase reporter

Background and aims Renal dysfunction is a potent risk factor for cardiovascular diseases, including stroke. This study aimed to evaluate the impact of admission estimated glomerular filtration rate (eGFR) levels on short-term (1-month) and long-term (1-year) mortality in patients with acute ischemic stroke. Methods From the Taiwan Stroke Registry data, we classified ischemic stroke patients, identified from April 2006 to December 2015, into 5 groups by eGFR at admission: ≥ 90, 60–89, 30–59, 15–29, and Results Among 52,732 ischemic stroke patients, 1480 died within one month. The 1-month mortality rate was over 5-fold greater in patients with eGFR Conclusions After acute ischemic stroke, patients with reduced eGFR are at elevated risks of short-term and long-term deaths in a graded relationship.

SUMMARY The neuromodulator dopamine (DA) plays a key role in motor control, motivated behaviors, and higher-order cognitive processes. Dissecting how these DA neural networks tune the activity of local neural circuits to regulate behavior requires tools for manipulating small groups of DA neurons. To address this need, we assembled a genetic toolkit that allows for an exquisite level of control over the DA neural network in Drosophila. To further refine targeting of specific DA neurons, we also created reagents that allow for the conversion of any existing GAL4 line into Split GAL4 or GAL80 lines. We demonstrated how this toolkit can be used with recently developed computational methods to rapidly generate additional reagents for manipulating small subsets or individual DA neurons. Finally, we used the toolkit to reveal a dynamic interaction between a small subset of DA neurons and rearing conditions in a social space behavioral assay., In Brief The rapid analysis of how dopaminergic circuits regulate behavior is limited by the genetic tools available to target and manipulate small numbers of these neurons. Xie et al. present genetic tools in Drosophila that allow rational targeting of sparse dopaminergic neuronal subsets and selective knockdown of dopamine signaling.

PurposeTo estimate the contribution of differences in demographics, comorbidity, insurance, tumor characteristics, and treatment to the overall mortality disparity between nonelderly black and white women diagnosed with early-stage breast cancer.Patients and MethodsExcess relative risk of all-cause death in black versus white women diagnosed with stage I to III breast cancer, expressed as a percentage and stratified by hormone receptor status for each variable (demographics, comorbidity, insurance, tumor characteristics, and treatment) in sequentially, propensity-scored, optimally matched patients by using multivariable hazard ratios (HRs).ResultsWe identified 563,497 white and black women 18 to 64 years of age diagnosed with stage I to III breast cancer from 2004 to 2013 in the National Cancer Data Base. Among women with hormone receptor–positive disease, who represented 78.5% of all patients, the HR for death in black versus white women in the demographics-matched model was 2.05 (95% CI, 1.94 to 2.17). The HR decreased to 1.93 (95% CI, 1.83 to 2.04), 1.54 (95% CI, 1.47 to 1.62), 1.30 (95% CI, 1.24 to 1.36), and 1.25 (95% CI, 1.19 to 1.31) when sequentially matched for comorbidity, insurance, tumor characteristics, and treatment, respectively. These factors combined accounted for 76.3% of the total excess risk of death in black patients; insurance accounted for 37.0% of the total excess, followed by tumor characteristics (23.2%), comorbidities (11.3%), and treatment (4.8%). Results generally were similar among women with hormone receptor–negative disease, although the HRs were substantially smaller.ConclusionMatching by insurance explained one third of the excess risk of death among nonelderly black versus white women diagnosed with early-stage breast cancer; matching by tumor characteristics explained approximately one fifth of the excess risk. Efforts to focus on equalization of access to care could substantially reduce ethnic/racial disparities in overall survival among nonelderly women diagnosed with breast cancer.

The objective of this essay is to examine baseball incubator is facilitated by governance failure of regional policies as opposed to initiating an alternative way of living for indigenous in Eastern Taiwan. With the perspective of regional planning, the discussion focuses on how space planning affects baseball industrial development from regional to local scale. Furthermore, the cultural meaning of baseball supplements the reason that baseball turns into the answer to this declined area. Finally, the case study of the Fantasy Association would provide a possible solution to the Eastern Taiwan, the home of indigenous baseball, in this epoch of deadlock.

Although axillary lymph node status has traditionally been a key factor in informing adjuvant breast cancer therapy recommendations, this information may be less relevant as our focus shifts more towards tumor biology, particularly in older patients where comorbidity influences treatment decisions and nodal staging and/or surgery may not improve outcomes. We examined patterns of axillary surgery and associations between axillary surgery and receipt of adjuvant treatment in older breast cancer patients. Women aged ≥ 65 years with clinically node-negative, stage I–II breast cancer treated between 2012 and 2013 were identified using the National Cancer Data Base. Using multivariable logistic regression, we examined associations between axillary surgery and age, adjusting for patient, clinical, and facility factors. We also examined receipt of adjuvant treatment by nodal surgery. Among 68,205 women, 40.1% were aged 65–70, 24.5% were 71–75, 17.4% were 76–80, and 18.0% were > 80. Overall, 91.2% had axillary surgery (67.8% sentinel lymph node biopsy, 11.7% axillary lymph node dissection, 11.7% unspecified/unknown axillary surgery); 88.0% of those aged ≥ 70 with lower risk, hormone receptor-positive tumors underwent axillary surgery. In adjusted analyses, compared to patients aged 65–70, increasing age was associated with lower odds of any axillary surgery (ages 71–75: OR 0.64, 95% CI 0.57–0.71; ages 76–80: OR 0.33, 95% CI 0.30–0.37; age > 80: OR 0.08, 95% CI 0.07–0.08). Axillary surgery was associated with higher odds of receipt of radiation after breast conservation and receipt of chemotherapy in human epidermal growth factor 2-positive disease. In a large nationwide dataset, the vast majority of older women with clinically node-negative breast cancer underwent axillary staging despite uncertainty about its impact on survival, particularly for those with lower-risk disease. Further study on how to tailor node assessment in older patients is warranted.

Incomplete lung cancer resection connotes poor prognosis; the incidence varies with patient demographic, clinical, and institutional factors. We sought to develop a valid, survival impactful, facility-based surgical quality metric that adjusts for related patient demographic and clinical characteristics.Facilities performing resections for patients diagnosed with stage I to IIIA non-small cell lung cancer in the National Cancer Data Base between 2004 and 2011 were identified. Multivariate logistic regression modeling was used to estimate the expected number of margin-positive cases by adjusting for patient risk mix and calculate the observed-to-expected ratio for each facility. Facilities were categorized as outperformers (observed-to-expected ratio less than 1, p0.05), nonoutliers (p0.05), and underperformers (observed-to-expected ratio greater than 1, p0.05); and their characteristics across performance categories were compared by χA total of 96,324 patients underwent surgery at 809 facilities. The overall observed margin-positive rate was 4.4%. Sixty-one facilities (8%) were outperformers, 644 (80%) were nonoutliers, and 104 (13%) were underperformers. One third (36%) of National Cancer Institute-designated facilities, 13% of academic comprehensive cancer programs, 5% of comprehensive community cancer programs, and 13% of "other" facilities achieved outperforming status but no community cancer programs did. Interestingly, 9% of National Cancer Institute-designated facilities and 11% of academic comprehensive cancer program facilities were underperformers. Adjusting for patient demographic and clinical characteristics, outperformers had a 5-year all-cause hazard ratio of 0.88 (95% confidence interval: 0.85 to 0.91, p0.0001) compared with nonoutliers, and 0.80 (95% confidence interval: 0.77 to 0.84, p0.0001) compared with underperformers.Facility performance in lung cancer surgery can be captured by the risk-adjusted margin-positivity rate, potentially providing a valid quality improvement metric.

// Chung-Hsing Chou 1, 2 , Jiunn-Tay Lee 1, 2 , Chun-Chieh Lin 1 , Yueh-Feng Sung 1 , Che-Chen Lin 3 , Chih-Hsin Muo 3 , Fu-Chi Yang 1 , Chi-Pang Wen 4 , I-Kuan Wang 5, 6, 7 , Chia-Hung Kao 5, 8 , Chung Y. Hsu 5 and Chun-Hung Tseng 9 1 Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China 2 Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China 3 Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan, Republic of China 4 Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan, Republic of China 5 Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, Republic of China 6 Department of Internal Medicine, College of Medicine, China Medical University, Taichung, Taiwan, Republic of China 7 Division of Kidney Disease, China Medical University Hospital, Taichung, Taiwan, Republic of China 8 Department of Nuclear Medicine, PET Center, China Medical University Hospital, Taichung, Taiwan, Republic of China 9 Department of Neurology, China Medical University Hospital, Taichung, Taiwan, Republic of China Correspondence to: Jiunn-Tay Lee, email: jiunntay@gmail.com Keywords: septicemia, infection, dementia, Alzheimer’s disease, non-Alzheimer dementias Received: May 17, 2017 Accepted: August 04, 2017 Published: September 15, 2017 ABSTRACT Background: Systemic infection has been linked to cognitive impairment. We hypothesized that patients with septicemia are predisposed to increased risks for developing dementia in a long-term setting. Methods: This observational, retrospective, longitudinal, nation-wide population-based study was conducted using the data deduced from Longitudinal Health Insurance Database (LHID) in Taiwan. All patients with septicemia hospitalized for the first time from 2001 to 2011 without prior dementia were included. The development of Alzheimer’s disease (AD) or non-Alzheimer dementias (NAD) in relation to the development of septicemia for each patient was recorded. An age- and sex-matched cohort without septicemia and without prior dementia served as the control. Septicemia, dementia, and other confounding factors were defined according to International Classification of Diseases Clinical Modification Codes. Cox proportional-hazards regressions were utilized to analyze adjusted hazard ratios. Results: Patients with septicemia had a higher risk for developing dementia based on hazard ratios (HRs) ( p 0.05). Furthermore, higher severity of septicemia was associated with increased risk of developing dementia. Conclusions: Our findings suggest that septicemia is associated with an increased risk in developing NAD but not AD. A likely causal role of septicemia in increasing the risk of NAD is suggested, according to the findings that patients with higher severity of septicemia carried greater risk of sustaining dementia.

We investigated the impact of serum cholesterol levels on 30-day mortality after ischemic stroke in dialysis patients.From the Taiwan Stroke Registry data, we identified 46,770 ischemic stroke cases, including 1101 dialysis patients and 45,669 nondialysis patients from 2006 to 2013.Overall, the 30-day mortality was 1.46-fold greater in the dialysis group than in the nondialysis group (1.75 versus 1.20 per 1000 person-days). The mortality rates were 1.64, .62, 2.82, and 2.23 per 1000 person-days in dialysis patients with serum total cholesterol levels of 120 mg/dL, 120-159 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively. Compared to dialysis patients with serum total cholesterol levels of 120-159 mg/dL, the corresponding adjusted hazard ratios of mortality were 4.20 (95% confidence interval [CI] = 1.01-17.4), 8.06 (95% CI = 2.02-32.2), and 6.89 (95% CI = 1.59-29.8) for those with cholesterol levels of 120 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively.Dialysis patients with serum total cholesterol levels of ≥160 mg/dL or 120 mg/dL on admission are at an elevated hazard of 30-day mortality after ischemic stroke.

Background Sleep-related movement disorders (SRMD) have been shown to increase the risk of cardiovascular diseases. However, the relationship between SRMD and stroke remains unclear. Aim To explore the relationship between SRMD and stroke in the general population. Design Two cohorts of patients with SRMD and without SRMD were followed up for the occurrence of hemorrhagic and ischemic stroke. Methods The study cohort enrolled 604 patients who were initially diagnosed as SRMD between 2000 and 2005. 2,416 age- and sex-matched patients without prior stroke were selected as the comparison cohort. A Cox-proportional hazard regression analysis was performed for multivariate adjustment. Results Patients with SRMD had a higher risk for developing all-cause stroke [adjusted hazard ratio (HR) = 2.29, 95% confidence interval (CI) = 1.42–3.80]. Patients of below 45 years old had the greatest stroke risk (HR = 4.03, 95% CI = 3.11–5.62), followed by patients aged ≥65 years (HR = 2.64, 95% CI = 1.12–3.44) and 45–64 years (HR = 1.07, 95% CI = 1.02–1.71). The age-stratified analysis suggested that the increased risk of hemorrhagic stroke was more significant than ischemic stroke among all age groups. Furthermore, males with SRMD were at greater risk to develop all-cause stroke (HR = 2.98, 95% CI = 1.74–4.50) than that of females (HR = 1.94, 95% CI = 1.01–3.77). Conclusions Patients with SRMD were found to have an increased risk of all-cause stroke along with a higher possibility of hemorrhagic stroke over ischemic stroke.

Numerous management options exist for patients with prostate cancer; however, recent trends and their influencing factors are not well described.To describe modern patterns of care and factors associated with management choice using the National Cancer Database.Patients with localized prostate cancer diagnosed between 2004 and 2012 were included and grouped according to National Comprehensive Cancer Network guidelines into low, intermediate, or high risk.Trend analyses and multivariate logistic regression was used to identify factors associated with management.There were 598 640 patients who met the study criteria; 36.3% were classified as low risk, 43.8% intermediate risk, and 20.0% high risk. Over the study period, among low-risk patients, observation increased from 9.2% to 21.3%, while radical prostatectomy (RP) increased from 29.5% to 51.1% (p0.001 for both). In contrast, external beam radiotherapy decreased from 24.3% to 14.5%, while brachytherapy decreased from 31.7% to 11.1%. A similar pattern was seen for patients with intermediate-risk or high-risk disease. Among high-risk patients, RP increased from 25.1% to 43.4% replacing external beam radiotherapy as the dominant therapy. On multivariate analysis, racial minorities, the uninsured, and low-income patients were less likely to receive RP. Low-risk patients in similar subgroups were significantly more likely to be observed. Limitations include potential miscoding or misclassification of variables.Patterns of care in localized prostate cancer are changing rapidly. While use of observation is increasing in low-risk groups, the use of RP is increasing across all risk groups with a concomitant decline in use of radiotherapy. Socioeconomic factors appear to influence management choice.In this report we identify a recent significant increase in the use of radical prostatectomy for prostate cancer patients. Socioeconomic factors such as race, insurance type, and income may affect treatments offered to and received by patients.

A rotating packed bed with blade packings was used to produce zinc oxide (ZnO) nanoparticles by precipitation. Precursors were firstly produced in a continuous liquid-liquid reaction of zinc chloride (ZnCl2) with sodium hydroxide (NaOH). The effects of the concentrations of ZnCl2 and NaOH, the flow rates of aqueous ZnCl2 and NaOH, and the rotational speed on the size of the precursors were studied. Experimental results indicate that increasing concentrations of ZnCl2 and NaOH, decreasing flow rates of aqueous ZnCl2 and NaOH, and decreasing the rotational speed reduced the size of the precursors. The smallest precursors were produced at a ZnCl2 concentration of 0.4 mol/L, an NaOH concentration of 0.8 mol/L, flow rates of aqueous ZnCl2 and NaOH of 0.3 L/min, and a rotational speed of 600 rpm. Then, the precursors were calcined at 400 °C for 1 h to generate ZnO nanoparticles with a mean size of 43 nm and a narrow size distribution. The detailed characterizations revealed that the as-produced ZnO nanoparticles were pure ZnO, which comprised a highly crystalline hexagonal wurtzite phase and exhibited a favorable optical property.

Introduction: Stroke pre-hospital delay has not improved over time. Hypothesis: Stroke Ready, a very brief (5 minute), theory based, peer-led, stroke preparedness intervention, will increase stroke response compared with a control intervention. Methods: We performed a randomized, single-blind controlled trial among adults in Flint, MI. The stroke preparedness intervention group received a Stroke Ready pamphlet and action plan, while the control group received stroke prevention materials - both delivered during a one-to-one interaction with a trained peer educator. Research staff, blinded to group intervention assignment, assessed baseline and immediate post-intervention outcomes. Primary outcome was change in stroke response (behavioral intent to call 911) using a community-modified stroke action test (range 0-12). Secondary outcome was change in stroke symptom recognition (range 0-8). We conducted descriptive analyses and used a linear regression model to evaluate the effect of the intervention on stroke response after adjustment for pre-intervention intent, age, education, race, marital status, history of stroke, stroke in someone they know and psychological constructs. Results: We enrolled 129 participants (74 intervention; 55 control). Mean age was 60 years (SD 14); 61% were women, 89% were African American and 19% were not high school graduates. Intervention participants had greater improvement in stroke response than control participants (figure 1), which remained after full adjustment (improvement in average score for stroke response was 1.7 higher in intervention participants than control participants, 95% CI 0.9-2.5, p Conclusion: The Stroke Ready very brief intervention increased stroke response. This new approach using a very brief, one-to-one interaction with trained peer educators is a promising, scalable, intervention to increase stroke response.

ObjectiveTo determine the utilization of genetic testing in patients seen by a neurologist within a large private insurance population.MethodsUsing the Optum health care claims database, we identified a cross-sectional cohort of patients who had been evaluated by a neurologist no more than 30 days before initial genetic testing. Within this group, we then categorized genetic testing between 2014 and 2016 on the basis of the Current Procedural Terminology (CPT) codes related to molecular and genetic testing. We also evaluated the International Classification of Disease Version 9 Clinical Code Classifications (ICD-9 CCS) associated with testing.ResultsFrom 2014 to 2016, a total of 45,014 claims were placed for 29,951 patients who had been evaluated by a neurologist within the preceding 30 days. Of these, 29,926 (66.5%) were associated with codes that were too nonspecific to infer what test was actually performed. Among those claims where the test was clearly identifiable, 7,307 (16.2%) were likely obtained for purposes of neurologic diagnosis, whereas the remainder (17.2%) was obtained for non-neurological purposes. An additional 3,793 claims (8.4%) wherein the test ordered could not be clearly identified were associated with a neurology-related ICD-9 CCS.ConclusionsAccurate assessment of genetic testing utilization using claims data is not possible given the high prevalence of nonspecific codes. Reducing the ambiguity surrounding the CPT codes and the actual testing performed will become even more important as more genetic tests become available.

Over one-third of older adults are accompanied by a companion to routine medical visits.1 Little is known about these companions for stroke survivors, a population who encounter short- and long-term disability and may benefit from medical care companions.

BACKGROUND People living with HIV (PLWH) are at an increased risk of developing several cancers, but to the authors' knowledge less is known regarding how HIV impacts the rate of progression to advanced cancer or death. METHODS The authors compared stage of disease at the time of presentation and mortality after diagnosis between 14,453 PLWH and 6,368,126 HIV-uninfected patients diagnosed with cancers of the oral cavity, stomach, colorectum, anus, liver, pancreas, lung, female breast, cervix, prostate, bladder, kidney, and thyroid and melanoma using data from the National Cancer Data Base (2004-2014). Polytomous logistic regression and Cox proportional hazards regression were used to evaluate the association between HIV, cancer stage, and stage-adjusted mortality after diagnosis, respectively. Regression models accounted for the type of health facility at which cancer treatment was administered and the type of individual health insurance. RESULTS HIV-infected patients with cancer were found to be more likely to be uninsured (HIV-infected: 5.0% vs HIV-uninfected: 3.3%; P

Background: Chronic inflammation has been linked to stroke, but it is not known whether atopic dermatitis (AD), a chronically inflammatory skin disease, is related to stroke. The aim of this study was to investigate the association of AD and stroke. Materials and Methods: In this population-based, cohort study, data were collected from a Longitudinal Health Insurance Database released from the National Health Research Institute in Taiwan in 2011. All patients with AD between 2000 and 2006 without prior stroke were included and an age- and gender-matched cohort without prior stroke, 4-fold of the AD sample size, was served as the control group. The two cohorts were followed until the end of 2010 for stroke incidence. Cox's proportional hazards regressions were used to assess the difference in stroke risk between groups. Results: During the follow-up period of 4–11 years, 471 (incidence: 4.46/1,000 person-years) and 1497 (incidence: 3.56/1,000 person-years) stroke incidents were noted in the study and control cohort, respectively. The patients with AD had an increased incidence of ischemic stroke (adjusted hazard ratio [HR]: 1.21; 95% confidence interval [CI]: 1.08–1.36) but not hemorrhagic stroke (adjusted HR: 0.97; 95% CI: 0.74–1.29). The severity of AD was significantly correlated with the risk of ischemic stroke. Conclusions: These results suggest that AD is independently associated with ischemic stroke but not with hemorrhagic stroke. The risk of ischemic stroke is correlated significantly with the severity of AD. Further research is necessary to explore the underlying mechanism.

Introduction In the U.S., people of different races/ethnicities have differences in cancer incidence, mortality, survival, stage at diagnosis, and receipt of treatment, resulting in variances in cancer burden. The burden of cancer in 2011 was assessed by race/ethnicity for 24 cancers using disability-adjusted life years (DALYs). Methods In 2014–2015, DALYs and their two components were estimated (years of life lost [YLLs] and years lived with disability) by race/ethnicity using population-based cancer registry data collected in 2013, vital statistics, and literature reviews. Results A total of 9.8 million DALYs (91% YLLs) were lost to cancer. Half of DALYs were due to lung (24%), breast (10%), colorectal (9%), and pancreatic (6%) cancers. Age-standardized DALY rate (ASR) ratios of non-Hispanic blacks (NHBs) over non-Hispanic whites (NHWs) for "all cancers" were 1.3 (95% CI=1.2, 1.4) times higher in men and 1.2 (95% CI=1.2, 1.3) times higher in women (ASR in NHBs 4,003 per 100,000 in men and 3,329 in women vs 3,088 and 2,758 in NHWs, respectively); ASRs were also higher in NHB for 15 cancers. Compared with NHWs, Hispanics and non-Hispanic Asians exhibited lower ASR for "all cancers" and common cancers, contrasting with a higher ASR for infection-related cancers (stomach, liver, cervix). Conclusions The cancer burden was highest in NHBs, followed by NHWs, Hispanics, and non-Hispanic Asians. In all races/ethnicities, the cancer burden was largely driven by YLLs, highlighting the need to prevent death at middle age through broad implementation of structural and behavioral measures of primary prevention, early detection, and treatment.

Disease-specific survival for testicular seminoma approaches 100%, even for those with node-positive disease. We sought to describe modern practice patterns, survival outcomes, and factors associated with postoperative therapy for patients with clinical stage (CS) IIA/B disease.Data on patients diagnosed with CS IIA/B seminoma from 1998 to 2012 were extracted from the National Cancer Data Base. Demographic, clinical, treatment, and payer characteristics were evaluated using multivariate regression to identify factors associated with receipt of chemotherapy or radiation therapy (RT) within 6 months of orchiectomy. Five-year Kaplan-Meier overall survival (OS) by CS and treatment was calculated. A Cox proportional hazards regression for 5-year OS was performed.A total of 1885 patients were included; 38.5% received chemotherapy and 61.5% received RT. On multivariate analysis, factors associated with receipt of postorchiectomy RT rather than chemotherapy included CS IIA (odds ratio [OR], 3.04; P.01) and community treatment setting (OR, 1.81-2.76; P.01). Reduced likelihood of receiving RT was associated with Medicaid insurance (OR, 0.50; P.01), more recent year of diagnosis (continuous OR, 0.93; P.01), and primary pathologic tumor 3/4 stage (OR, 0.47; P.01). On multivariate Cox regression, decreased 5-year OS was associated with receipt of chemotherapy in CS IIA patients (hazard ratio, 13.33; P.01) but not in CS IIB patients (hazard ratio, 1.39; P = .45). For CS IIA, 5-year OS was 99.4% for orchiectomy and RT versus 91.2% for orchiectomy and chemotherapy (log-rank P.01). For CS IIB, 5-year OS was 96.1% for orchiectomy and RT versus 92.8% for orchiectomy and chemotherapy (log-rank P = .08).Consistent with national guideline recommendations, our analysis supports preferred status for RT in CS IIA. In addition, these data also support use of RT for CS IIB. CS, treatment year, primary pathologic tumor stage, insurance, and facility type were associated with type of postoperative therapy. Longer follow-up to account for potential late effects of treatment is needed.

The CRISPR/Cas9 system has revolutionized genomic editing. The Cas9 endonuclease targets DNA via an experimentally determined guide RNA (gRNA). This results in a double-strand break at the target site . We generated transgenic Drosophila melanogaster in which the CRISPR/Cas9 system was used to target a GAL4 transgene in vivo. To our surprise, progeny whose genomes did not contain CRISPR/Cas9 components were still capable of mutating GAL4 sequences. We demonstrate this effect was caused by maternal deposition of Cas9 and gRNAs into the embryo, leading to extensive GAL4 mutations in both somatic and germline tissues. This serves as a cautionary observation on the effects of maternal contributions when conducting experiments using genomically encoded CRISPR/Cas9 components. These results also highlight a mode of artificial inheritance in which maternal contributions of DNA editing components lead to transmissible mutant defects even in animals whose genomes lack the editing components. We suggest calling this a dominant maternal effect to reflect it is caused by the gain of maternally contributed products. Models of CRISPR-mediated gene drive will need to incorporate dominant maternal effects in order to accurately predict the efficiency and dynamics of gene drive in a population.

Objective To investigate the association between rheumatoid arthritis (RA) and the risk of developing Parkinson disease (PD). Patients and Methods This retrospective cohort study was conducted from January 1, 1998, through December 31, 2010, using data from the Taiwan National Health Insurance Research Database. We identified 33,221 patients with newly diagnosed RA and 132,884 randomly selected age- and sex-matched patients without RA. A multivariable Cox proportional hazards regression model was used to evaluate the risk of developing PD in the RA cohort. Results The multivariable Cox proportional hazards regression analysis revealed an adjusted hazard ratio of 0.65 (95% CI, 0.58-0.73) for the development of PD in the RA cohort relative to the non-RA cohort. The cumulative incidence of PD was 2.42% lower in the RA cohort than in the non-RA cohort. The risk reduction of PD development in patients affected with RA was independent of treatment with disease-modifying antirheumatic drugs (DMARDs); subgroup analysis of patients treated with biologic DMARDs revealed further risk reduction (adjusted hazard ratio, 0.57; 95% CI, 0.41-0.79). Conclusion Patients with RA have a reduced risk of developing PD. This risk reduction was independent of treatment with DMARDs; however, biologic DMARDs appear to further reduce this risk. Further research is necessary to explore the underlying mechanism.

Mosquitoes are vectors for multiple infectious human diseases and use a variety of sensory cues (olfactory, temperature, humidity and visual) to locate a human host. A comprehensive understanding of the circuitry underlying sensory signalling in the mosquito brain is lacking. Here we used the Q-system of binary gene expression to develop transgenic lines of Anopheles gambiae in which olfactory receptor neurons expressing the odorant receptor co-receptor (Orco) gene are labelled with GFP. These neurons project from the antennae and maxillary palps to the antennal lobe (AL) and from the labella on the proboscis to the suboesophageal zone (SEZ), suggesting integration of olfactory and gustatory signals occurs in this brain region. We present detailed anatomical maps of olfactory innervations in the AL and the SEZ, identifying glomeruli that may respond to human body odours or carbon dioxide. Our results pave the way for anatomical and functional neurogenetic studies of sensory processing in mosquitoes., Mosquitoes use olfactory cues to locate their host. Here, Riabinina et al. use genetic labelling of olfactory receptor neurons in the malaria vector Anopheles gambiae to show that these neurons project to the antennal lobe, a known insect olfactory centre, and the subesophageal zone, a region previously linked to gustatory processing.

BACKGROUND Cytology is an accurate, safe, cost-effective, and guideline-recommended method for pancreatic cancer diagnosis, particularly for unresectable disease. However, to the authors’ knowledge, the frequency and determinants of its use have not been described to date. The current study examined patterns of cytological diagnosis among patients with unresectable pancreatic cancer by treatment facility type and by patient characteristics. METHODS The prevalence of definitive cytological diagnosis (cytology only, without confirmatory histology) versus histological diagnosis (with or without accompanying cytology) was examined in National Cancer Data Base records of 13,657 patients diagnosed with unresectable (American Joint Committee on Cancer stages III and IV) pancreatic cancer in 2011 and 2012 who did not undergo surgical treatment (mode of diagnosis could not be ascertained for surgical patients). Associations between definitive cytological diagnosis and patient and facility characteristics were assessed using multivariable marginal logistic regression models and expressed as odds ratios (OR) and 95% confidence intervals (95% CIs). RESULTS Overall, 26.8% of unresectable pancreatic cancer cases were definitively diagnosed with cytology. The prevalence of cytological diagnosis ranged from 16.5% in community cancer programs and 22.6% in comprehensive community cancer programs to 31.3% in academic/teaching/research cancer programs and 43.2% in National Cancer Institute-designated cancer programs (P

The number of cancer survivors continues to increase because of both advances in early detection and treatment and the aging and growth of the population. For the public health community to better serve these survivors, the American Cancer Society and the National Cancer Institute collaborate to estimate the number of current and future cancer survivors using data from the Surveillance, Epidemiology, and End Results cancer registries. In addition, current treatment patterns for the most prevalent cancer types are presented based on information in the National Cancer Data Base and treatment-related side effects are briefly described. More than 15.5 million Americans with a history of cancer were alive on January 1, 2016, and this number is projected to reach more than 20 million by January 1, 2026. The 3 most prevalent cancers are prostate (3,306,760), colon and rectum (724,690), and melanoma (614,460) among males and breast (3,560,570), uterine corpus (757,190), and colon and rectum (727,350) among females. More than one-half (56%) of survivors were diagnosed within the past 10 years, and almost one-half (47%) are aged 70 years or older. People with a history of cancer have unique medical and psychosocial needs that require proactive assessment and management by primary care providers. Although there are a growing number of tools that can assist patients, caregivers, and clinicians in navigating the various phases of cancer survivorship, further evidence-based resources are needed to optimize care. CA Cancer J Clin 2016;66:271-289. © 2016 American Cancer Society.

BACKGROUND The treatment of patients with advanced stage laryngeal cancer includes surgery or concurrent chemoradiation (CRT). Although CRT has become more common in recent years, to the authors' knowledge, the effectiveness of complete CRT in improving survival over surgery has not been studied. METHODS The authors examined patients in the Surveillance, Epidemiology, and End Results (SEER)-Medicare claims-linked data set with locoregional laryngeal cancer who were diagnosed between 1997 and 2007. Multivariate Cox proportional hazard analyses were conducted to compare overall and cause-specific 5-year survival rates between treatment modalities, adjusting for patient sociodemographic and clinical characteristics. A propensity score-matched subcohort also was used to compare survival. RESULTS Of the 3212 patients in the study cohort, 42% underwent surgery and 18% underwent CRT. Only approximately one-quarter of patients who were treated with CRT completed the courses. In adjusted analyses, the authors were unable to reject the null hypothesis of no difference in 5-year all-cause or cause-specific mortality risk between patients treated with surgery and patients undergoing complete CRT (hazards ratio, 1.25 [95% confidence interval, 0.91-1.71; P = .16] and hazard ratio, 1.41 [95% confidence interval, 0.9-2.2; P = .14], respectively). Older age, not currently married, Medicaid eligibility, and prior cancer history were found to be associated with a higher risk of mortality (P

BACKGROUND Patients with cancer who are infected with the human immunodeficiency virus (HIV) are less likely to receive cancer treatment compared with HIV-uninfected individuals. However, to the authors' knowledge, the impact of insurance status and comorbidities is unknown. METHODS Data from the National Cancer Data Base were used to study nonelderly adults diagnosed with several common cancers from 2003 to 2011. Cancer treatment was defined as chemotherapy, surgery, radiotherapy, or any combination during the first course of treatment. Multivariate logistic regression was used to examine associations between HIV status and lack of cancer treatment, and identify predictors for lack of treatment among HIV-infected patients. RESULTS A total of 10,265 HIV-infected and 2,219,232 HIV-uninfected cases were included. In multivariate analysis, HIV-infected patients with cancer were found to be more likely to lack cancer treatment for cancers of the head and neck (adjusted odds ratio [aOR], 1.48; 95% confidence interval [95% CI], 1.09-2.01), upper gastrointestinal tract (aOR, 2.62; 95% CI, 2.04-3.37), colorectum (aOR, 1.70; 95% CI, 1.17-2.48), lung (aOR, 2.46; 95% CI, 2.19-2.76), breast (aOR, 2.14; 95% CI, 1.16-3.98), cervix (aOR, 2.81; 95% CI, 1.77-4.45), prostate (aOR, 2.16; 95% CI, 1.69-2.76), Hodgkin lymphoma (aOR, 1.92; 95% CI, 1.66-2.22), and diffuse large B-cell lymphoma (aOR, 1.82; 95% CI, 1.65-2.00). Predictors of a lack of cancer treatment among HIV-infected individuals varied by tumor type (solid tumor vs lymphoma), but black race and a lack of private insurance were found to be predictors for both groups. CONCLUSIONS In the United States, HIV-infected patients with cancer appear to be less likely to receive cancer treatment regardless of insurance and comorbidities. To the authors' knowledge, the current study is the largest study of cancer treatment in HIV-infected patients with cancer in the United States and provides evidence of cancer treatment disparities even after controlling for differences with regard to insurance status and comorbidities. Further work should focus on addressing differential cancer treatment. Cancer 2016;122:2399–2407. © 2016 American Cancer Society.

PURPOSE This study aimed to characterize changes in regional cerebral blood flow (rCBF) in patients who experienced carbon monoxide (CO) poisoning and subsequently developed severe delayed neuropsychiatric sequelae (DNS) with akinetic mutism. We determined whether these changes were reversible in parallel with improvements in neuropsychological function in response to treatment, including hyperbaric oxygen therapy. METHODS Patients who developed severe DNS with akinetic mutism after acute CO intoxication between 2007 and 2011 were enrolled. Tc-ECD brain SPECT findings were compared between the patients with severe akinetic mutism and age-matched control subjects to characterize the pattern of rCBF. Perfusion SPECT was correlated with clinical outcomes after treatment with statistical parametric mapping (SPM8); the height threshold was P < 0.01 at peak level, and the corrected false discovery rate was P < 0.05 at the cluster level. RESULTS Seven patients with akinetic mutism were analyzed. All patients had neurological symptoms caused by acute CO exposure, and all recovered to nearly normal daily function after initial treatments. In all cases, after a "lucid interval," DNS progressed to akinetic mutism. The SPECT images acquired at the onset of akinetic mutism demonstrated variable hypoperfusion in frontal-temporal-parietal regions, with the greatest severity in the left temporal-parietal regions. In parallel, we performed functional neuropsychiatric tests. After treatment, the brain SPECT showed significantly fewer hypoperfusion regions, and neuropsychiatric tests showed dramatically improved function. CONCLUSIONS Our findings demonstrated both cerebral cortical and subcortical injuries in patients with CO-induced akinetic mutism. Improvement in rCBF correlated well with functional recovery after treatment.

Resistive switching memory devices with superior properties are possibly used in next-generation nonvolatile memory to replace the flash memory. In addition, flexible electronics has also attracted much attention because of its light-weight and flexibility. Therefore, an Al/Al2O3/TiO2/Al/PES flexible resistive switching memory is employed in this study. The resistive switching characteristics and stability of the flexible device are improved by inserting the Al2O3 film. The resistive switching of the flexible device can be repeated over hundreds of times after the bending test. A possible resistive switching model of the flexible device is also proposed. In addition, the non-volatility of the flexible device is demonstrated. Based on our research results, the proposed Al2O3/TiO2-based resistive switching memory is possibly used in next-generation flexible electronics and nonvolatile memory applications.

Trimodality therapy (chemoradiation and surgery) is the standard of care for stage II/III rectal cancer but nearly one third of patients do not receive radiation therapy (RT). We examined the relationship between the density of radiation oncologists and the travel distance to receipt of RT.A retrospective study based on the National Cancer Data Base identified 26,845 patients aged 18 to 80 years with stage II/III rectal cancer diagnosed from 2007 to 2010. Radiation oncologists were identified through the Physician Compare dataset. Generalized estimating equations clustering by hospital service area was used to examine the association between geographic access and receipt of RT, controlling for patient sociodemographic and clinical characteristics.Of the 26,845 patients, 70% received RT within 180 days of diagnosis or within 90 days of surgery. Compared with a travel distance of12.5 miles, patients diagnosed at a reporting facility who traveled ≥50 miles had a decreased likelihood of receipt of RT (50-249 miles, adjusted odds ratio 0.75, P.001; ≥250 miles, adjusted odds ratio 0.46; P=.002), all else being equal. The density level of radiation oncologists was not significantly associated with the receipt of RT. Patients who were female, nonwhite, and aged ≥50 years and had comorbidities were less likely to receive RT (P.05). Patients who were uninsured but self-paid for their medical services, initially diagnosed elsewhere but treated at a reporting facility, and resided in Midwest had an increased the likelihood of receipt of RT (P.05).An increased travel burden was associated with a decreased likelihood of receiving RT for patients with stage II/III rectal cancer, all else being equal; however, radiation oncologist density was not. Further research of geographic access and establishing transportation assistance programs or lodging services for patients with an unmet need might help decrease geographic barriers and improve the quality of rectal cancer care.

Brain degeneration in patients with Alzheimer&rsquo, s disease (AD) results from the accumulation of pathological amyloid- (A&beta, ) plaques and tau protein tangles, leading to altered plasma levels of biomarkers. However, few studies have investigated the association between plasma biomarkers and cognitive impairment in patients with AD. In this cross-sectional study, we investigated correlations between mini-mental state examination (MMSE) scores and levels of plasma biomarkers in patients with amnestic mild cognitive impairment (aMCI) and AD. Thirteen individuals with normal cognition, 40 patients with aMCI, and 37 patients with AD were enrolled. Immunomagnetic reduction was used to assess the levels of plasma biomarkers, including amyloid A1-40, A1-42, total tau protein (t-Tau), and phosphorylated tau protein (threonine 181, p-Tau181). Our analysis revealed a significant negative correlation between MMSE and both measures of tau, and a trend toward negative correlation between MMSE and A1-42. In a longitudinal study involving three patients with aMCI and two patients with AD, we observed strong negative correlations (r &lt, &minus, 0.8) between changes in MMSE scores and plasma levels of t-Tau. Our results suggest that plasma levels of t-Tau and p-Tau181 can be used to assess the severity of cognitive impairment in patients with AD. Furthermore, the results of our preliminary longitudinal study suggest that levels of t-Tau can be used to monitor the progression of cognitive decline in patients with aMCI/AD.