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To achieve WHO targets for the elimination of hepatitis C virus (HCV) as a public threat, an increased uptake of HCV treatment among people who inject drugs (PWID) is urgently needed. Optimal HCV co-located treatment models for PWID have not yet been identified. We aimed to compare two patient-centred models of HCV care in PWID with active drug use.We did a pragmatic randomised controlled trial at eight US cities in eight opioid treatment programmes and 15 community health centres. PWID actively injecting within 90 days of study entry were randomly assigned (1:1) to either patient navigation or modified directly observed therapy (mDOT) using computer-generated variable block sizes of 2-6 stratified by city, clinical settings, and cirrhosis status. The randomisation code was concealed, in a centralised REDCap database platform, from all investigators and research staff except for an authorised data manager at the data coordinating centre. All participants received a fixed-dose combination tablet (sofosbuvir 400 mg plus velpatasvir 100 mg) orally once daily for 12 weeks. The primary outcome was sustained virological response (SVR; determined by chart review between 70 days and 365 days after end of treatment and if unavailable, by study blood draws), and secondary outcomes were treatment initiation, adherence (measured by electronic blister packs), and treatment completion. Analyses were conducted within the modified intention-to-treat (mITT; all who initiated treatment), intention-to-treat (all who were randomised), and per-protocol populations. This trial is registered with ClinicalTrials.gov, NCT02824640.Between Sept 15, 2016, and Aug 14, 2018, 1891 individuals were screened and 1136 were excluded (213 declined to participate and 923 did not meet the eligibility criteria). We randomly assigned 755 participants to patient navigation (n=379) or mDOT (n=376). In the mITT sample of participants who were randomised and initiated treatment (n=623), 226 (74% [95% CI 69-79]) of 306 participants in the mDOT group and 236 (76% [69-79]) of 317 in the patient navigation group had an SVR, with no significant difference between the groups (adjusted odds ratio [AOR] 0·97 [95% CI 0·66-1·42]; p=0·35). In the ITT sample (n=755), 226 (60% [95% CI 55-65]) of 376 participants in the mDOT group and 236 (62% [57-67]) of 379 in the patient navigation group had an SVR (AOR 0·92 [0·68-1·25]; p=0·61) and in the per-protocol sample (n=501), 226 (91% [87-94]) of 248 participants in the mDOT group and 235 (93% [89-96]) of 253 in the patient navigation group had an SVR (AOR 0·79 [0·41-1·55]; p=0·44). 306 (81%) of 376 participants in the mDOT group and 317 (84%) of 379 participants in the patient navigation group initiated treatment (AOR 0·86 [0·58-1·26]; p=0·44) and, among those, 251 (82%) participants in the mDOT group and 264 (83%) participants in the patient navigation group completed treatment (AOR 0·90 [0·58-1·39]; p=0·63). Mean daily adherence was higher in the mDOT group (78% [95% CI 75-81]) versus the patient navigation group (73% [70-77]), with a difference of 4·7% ([1·9-7·4]; p=0·0010). 421 serious adverse events were reported (217 in the mDOT group and 204 in the patient navigation group), with the most common being hospital admission (176 in the mDOT group vs 161 in the patient navigation group).In this trial of active PWID, both models resulted in high SVR. Although adherence was significantly higher in the mDOT group versus the patient navigation group, there was no significant difference in SVR between the groups. Increases in adherence and treatment completion were associated with an increased likelihood of SVR. These results suggest that active PWID can reach high SVRs in diverse settings with either mDOT or patient navigation support.Patient-Centered Outcomes Research Institute, Gilead Sciences, Quest Diagnostics, Monogram Biosciences, and OraSure Technologies.

Previous studies from our lab have demonstrated age-related changes in vascular structure/function in posterior cerebral arteries (PCA) and left common carotid artery (CA) in male and female mice expressing human-ApoE targeted replacement of APOE3 (B6.129P2-Apoetm2(APOE*3)MaeN8) and APOE4 (B6.129P2-Apoetm3(APOE*4)Mae N8) (Taconic Labs). Therefore, we hypothesized that similar changes may be observed in the peripheral circulation. We isolated 3rd-order mesenteric arteries (MA) from young (Y, 3 to 4 mo) and adult (A, 7 to 10 mo), male and female mice expressing hPOE3 and hAPOE4. Mesenteric artery segments (5-8 mm in length) were isolated and cannulated on an arteriograph to assess vascular mechanical properties (lumen diameter (LD), wall thickness (WT), wall cross-sectional area (CSA), wall:lumen ratio (WL), distensibility (Dist), and stress/strain (SvS) under passive conditions (Ca2+-free Krebs + diltiazem) at intraluminal pressures ranging from 10-140 mmHg. Data were analyzed using two-way ANOVA, Student’s t-test, and analysis of nonlinear fit. Values were considered statistically different at P Support: ABRC/ADHS18-205211 (DME, CBJ), Arizona Alzheimer's Consortium (funded by the Arizona Department of Health Services, Contract No. CTR040636) and matching funds from Midwestern University (DME), Biomedical Sciences Program (JF, KW, JD, DME), Biomedical Sciences Start-up Funds (DME) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Traumatic brain injury (TBI) is increasingly recognised as being responsible for a substantial proportion of the global burden of disease. Neurosurgical interventions are an important aspect of care for patients with TBI, but there is little epidemiological data available on this patient population. We aimed to characterise differences in casemix, management, and mortality of patients receiving emergency neurosurgery for TBI across different levels of human development. Methods: We did a prospective observational cohort study of consecutive patients with TBI undergoing emergency neurosurgery, in a convenience sample of hospitals identified by open invitation, through international and regional scientific societies and meetings, individual contacts, and social media. Patients receiving emergency neurosurgery for TBI in each hospital's 30-day study period were all eligible for inclusion, with the exception of patients undergoing insertion of an intracranial pressure monitor only, ventriculostomy placement only, or a procedure for drainage of a chronic subdural haematoma. The primary outcome was mortality at 14 days postoperatively (or last point of observation if the patient was discharged before this time point). Countries were stratified according to their Human Development Index (HDI)—a composite of life expectancy, education, and income measures—into very high HDI, high HDI, medium HDI, and low HDI tiers. Mixed effects logistic regression was used to examine the effect of HDI on mortality while accounting for and quantifying between-hospital and between-country variation. Findings: Our study included 1635 records from 159 hospitals in 57 countries, collected between Nov 1, 2018, and Jan 31, 2020. 328 (20%) records were from countries in the very high HDI tier, 539 (33%) from countries in the high HDI tier, 614 (38%) from countries in the medium HDI tier, and 154 (9%) from countries in the low HDI tier. The median age was 35 years (IQR 24–51), with the oldest patients in the very high HDI tier (median 54 years, IQR 34–69) and the youngest in the low HDI tier (median 28 years, IQR 20–38). The most common procedures were elevation of a depressed skull fracture in the low HDI tier (69 [45%]), evacuation of a supratentorial extradural haematoma in the medium HDI tier (189 [31%]) and high HDI tier (173 [32%]), and evacuation of a supratentorial acute subdural haematoma in the very high HDI tier (155 [47%]). Median time from injury to surgery was 13 h (IQR 6–32). Overall mortality was 18% (299 of 1635). After adjustment for casemix, the odds of mortality were greater in the medium HDI tier (odds ratio [OR] 2·84, 95% CI 1·55–5·2) and high HDI tier (2·26, 1·23–4·15), but not the low HDI tier (1·66, 0·61–4·46), relative to the very high HDI tier. There was significant between-hospital variation in mortality (median OR 2·04, 95% CI 1·17–2·49). Interpretation: Patients receiving emergency neurosurgery for TBI differed considerably in their admission characteristics and management across human development settings. Level of human development was associated with mortality. Substantial opportunities to improve care globally were identified, including reducing delays to surgery. Between-hospital variation in mortality suggests changes at an institutional level could influence outcome and comparative effectiveness research could identify best practices. Funding: National Institute for Health Research Global Health Research Group.

Posterior fossa dural arteriovenous fistulas (dAVFs) are rare vascular lesions with variable risk of hemorrhage, mostly depending on the pattern of the venous drainage. While endovascular embolization is the mainstay treatment for most dAVFs, some posterior fossa lesions require a multidisciplinary approach including surgery. The goal of our study was to examine the outcome of an interdisciplinary treatment for posterior fossa dAVFs. A retrospective review of patients treated for posterior fossa dAVFs was conducted. A total of 28 patients with a mean age of 57.8 years were included. Patients presented with a Cognard grade I in 2 (7%), II a in 5 (18 %), II b in 7 (25%), II a + b in 5 (18%), III in 3 (11%), and IV in 6 (21%) cases. Hemorrhage was the initial presentation in 2 (22%) patients with Cognard grade IV, in 3 with Cognard grade III (33%), in 1 (11%) with Cognard II a + b, and 3 (33%) with Cognard II b. A complete angiographic cure was achieved in 24 (86%) patients—after a single-session embolization in 16 (57%) patients, multiple embolization sessions in 2 (7%), a multimodal treatment with embolization and surgical disconnection in 3 (11%), and with an upfront surgery in 3 (11%). Complete long-term obliteration was demonstrated in 18/22 (82%) at the mean follow-up of 17 months. Fistulas were converted into asymptomatic Cognard I lesion in 4 (14%) patients. Posterior fossa dAVFs represent a challenging vascular pathology; however, despite their complexity, an interdisciplinary treatment can achieve high rates of angiographic and symptomatic cure with low morbidity and mortality rates. Long-term surveillance is warranted as late recurrences may occur.

Background Hemifacial spasm (HFS) is a neuromuscular disorder resulting from cranial nerve VII compression at the root entry zone, characterized by brief, involuntary, progressive spasms of muscles on one side of face. The cisternal part of cranial nerve VII myelinated by Schwann cells is considered relatively resistant to compression. Rarely, direct compression over this segment without coexistent root entry zone compression may also result in HFS. An aberrant vessel posterior inferior cerebellar artery/anterior inferior cerebellar artery loop remains the leading cause of compression at this location. Cerebellopontine angle tumors or cysts may affect cranial nerve VII distally. However, bony meatal stenosis with pure distal facial nerve compression leading to HFS in the absence of other clinical symptoms has not been reported. Case Description A 53-year-old woman presented with worsening left HFS for 9 years despite multiple trials of medical therapy, which severely impeded her social life and occupation. Temporal bone computed tomography revealed severe stenosis of the left internal auditory meatus (2.36 mm) compared with the right side (4.67 mm). Under three-dimensional exoscope guidance, a left retrosigmoid suboccipital craniotomy was performed, the posterior bony wall of the internal auditory canal was drilled to decompress the canal, and durotomy was performed to release the contents. Her symptoms resolved without developing facial weakness or hearing deficits. Conclusions An aberrant anterior inferior cerebellar artery vascular loop is usually the most frequent lesion causing compression of the distal cisternal part of the facial nerve. However, other purely distal or coexistent lesions must be actively sought for both in preoperative radiologic images and during surgery.

Objective: Treatment for hepatitis C virus (HCV) infection is highly effective; however, people who inject drugs (PWID), the population most affected by HCV, may encounter barriers to treatment. We examined the cascade of care for HCV infection among young adult PWID in northern New Mexico, to help identify gaps and opportunities for HCV treatment intervention. Methods: Young adults (aged 18-29 y) who self-reported injection drug use in the past 90 days were tested for HCV antibodies (anti-HCV) and HCV RNA. We asked participants with detectable RNA to participate in an HCV education session, prior to a referral to a local health care provider for treatment follow-up, and to return for follow-up HCV testing quarterly for 1 year. We measured the cascade of care milestones ranging from the start of screening to achievement of sustained virologic response (SVR). Results: Among 238 participants, the median age was 26 years and 133 (55.9%) were men. Most (90.3%) identified as Hispanic. Of 109 RNA-positive participants included in the cascade of care assessment, 84 (77.1%) received their results, 82 (75.2%) participated in the HCV education session, 61 (56.0%) were linked to care through a medical appointment, 27 (24.8%) attended the HCV treatment appointment, 13 (11.9%) attended their follow-up appointment, 6 (5.5%) initiated treatment, 3 (2.8%) completed treatment, and 1 (0.9%) achieved SVR. Conclusions: We observed a steeply declining level of engagement at each milestone step of the cascade of care after detection of HCV infection, resulting in a suboptimal level of HCV treatment and cure. Programs that can streamline testing and expand access to treatment from trusted health care providers are needed to improve the engagement of PWID in HCV treatment.

Increasingly, people who inject drugs (PWID) infected with hepatitis C virus (HCV) are gaining access to highly effective direct-acting antiviral agents (DAAs). Although past studies examined patient experiences with interferon-based treatments, few have explored patient experiences with these new generation therapeutics. Research and real world experience indicate that many PWID can be successfully treated with the new DAAs. Yet a substantial minority fail to complete treatment or achieve only suboptimal adherence. This qualitative study examines experiences with treatment among participants in Project HERO, a large multisite trial designed to compare treatment delivery methods for DAAs. We explored treatment experiences among HERO participants, with the goal of understanding potential barriers to treatment engagement and completion.We conducted qualitative interviews with a sample of 21 participants, including 14 who completed HCV treatment and 7 participants who discontinued treatment before the end of the 12-week medication course. The first phase of the analysis was descriptive, examining participants' life experiences, histories of disease and treatment seeking, experiences with the program, and barriers to treatment completion. The second phase of the analysis examined differences between completers and noncompleters.Participants offered a variety of reasons for seeking treatment. Both groups of participants reported highly positive experiences of the HERO trial. Participants described research staff as caring, respectful, and nonjudgmental. Substance use was reported by both groups, yet completers described "manageable" substance use, while noncompleters described substance use that sapped their energy and motivation. Shame over drug use was a barrier to treatment completion. Homelessness and a reported lack of social support were much more common in the noncompleter group.Reasons for noncompletion were not related to features of the clinical trial or treatment program. Our results indicate the importance of: 1) recognizing and addressing severe social and economic challenges such as homelessness; and 2) building a program culture of respect and compassion in treatment programs for PWID infected with HCV.

OBJECTIVEIn patients with aneurysmal subarachnoid hemorrhage (aSAH), poor outcomes have been shown to be correlated with subsequent cerebral vasospasm (CV) and delayed cerebral ischemia (DCI). The identification of novel biomarkers may aid in the prediction of which patients are vulnerable to developing vasospasm, cerebral ischemia, and neurological deterioration.METHODSIn this prospective clinical study at North Shore University Hospital, patients with aSAH or normal pressure hydrocephalus (NPH) with external ventricular drains were enrolled. The concentration of macrophage migration inhibitory factor (MIF) in CSF was assessed for correlation with CV or DCI, the primary outcome measures.RESULTSTwenty-five patients were enrolled in the aSAH group and 9 were enrolled in the NPH group. There was a significant increase in aggregate CSF MIF concentration in patients with aSAH versus those with NPH (24.4 ± 19.2 vs 2.3 ± 1.1 ng/ml, p < 0.0002). Incidence of the day of peak MIF concentration significantly correlated with the onset of clinical vasospasm (rho = 0.778, p < 0.0010). MIF concentrations were significantly elevated in patients with versus those without evidence of DCI (18.7 ± 4.93 vs 8.86 ± 1.28 ng/ml, respectively, p < 0.0025). There was a significant difference in MIF concentrations between patients with infection versus those without infection (16.43 ± 4.21 vs 8.5 ± 1.22 ng/ml, respectively, p < 0.0119).CONCLUSIONSPreliminary evidence from this study suggests that CSF concentrations of MIF are correlated with CV and DCI. These results, however, could be confounded in the presence of clinical infection. A study with a larger patient sample size is necessary to corroborate these findings.

Purpose Stereotactic body radiation therapy (SBRT) is a common treatment option for patients with metastatic tumors of the spine. The optimal treatment-, tumor-, and patient-specific characteristics necessary to achieve durable outcomes remain less well understood given the heterogeneous nature of the patient population this modality typically serves. The objective of this analysis was to better understand the determinants underlying SBRT spine treatment outcomes. Methods and Materials A total of 127 patients with 287 spine tumors were treated between March 2010 and May 2015. The median total doses for single-fraction and hypofractionated courses of treatment were 16 Gy (range, 16-20 Gy) and 24 Gy (range, 16-40 Gy), respectively. Radiologic local control and numeric pain score data were measured, and univariate and multivariate analyses were done to determine factors predictive of treatment response. Results Median follow-up was 5.9 months (range, 1-61 months). Radiologic local control was achieved in 84.7% of patients at 6 months and in 74.7% of patients at 1 year. Local control was found to be affected by the Spinal Instability Neoplastic Score, and was worse in patients with scores ≥7 (hazard ratio [HR]: 4.25; 95% confidence interval [CI], 1.57-11.51). Patients who required upfront surgical intervention to alleviate spinal cord compression, address mechanical spinal instability, or both had worse local control than those who did not require surgery (HR: 2.32; 95% CI, 1.04-5.17). Patients treated with a hypofractionated course compared with a single fraction had worse radiologic local control (HR: 2.63; 95% CI, 1.27-5.45). No patients developed radiation-induced myelitis after treatment, and the vertebral compression fracture rate was 9.1% after SBRT. Conclusions Patients with potentially unstable spines or needing upfront spinal surgery before SBRT are less likely to achieve durable radiologic local control. Additionally, patients treated with single-fraction regimens have improved local control compared with those treated with hypofractionated radiation.

The Capital District Asylum Collaborative (CDAC) is an organization that provides psychiatric and medical evaluations to be used as forensic evidence to support asylum applications. Our study assesses the demographics and traumas experienced by CDAC clients. In this retrospective study, 23 completed affidavits for clients evaluated through CDAC between the years 2016 and 2020 were analyzed for demographics, trauma experience, and psychiatric diagnosis given. Most clients experienced at least 4 different forms of trauma. Nearly 78% of clients experienced beating to the body, 43% were raped, 56.5% experienced other forms of sexual abuse or humiliation, 47.8% experienced forced separation from family, and 39.1% experienced illness and poor access to care. Majority of clients were diagnosed with comorbidities most commonly major depressive disorder and post-traumatic stress disorder. This analysis has provided us guidance on how to establish continuing care options for future clients evaluated at CDAC.

BACKGROUND: A safe and effective vaccine to prevent chronic hepatitis C virus (HCV) infection is a critical component of efforts to eliminate the disease. METHODS: In this phase 1–2 randomized, double-blind, placebo-controlled trial, we evaluated a recombinant chimpanzee adenovirus 3 vector priming vaccination followed by a recombinant modified vaccinia Ankara boost; both vaccines encode HCV nonstructural proteins. Adults who were considered to be at risk for HCV infection on the basis of a history of recent injection drug use were randomly assigned (in a 1:1 ratio) to receive vaccine or placebo on days 0 and 56. Vaccine-related serious adverse events, severe local or systemic adverse events, and laboratory adverse events were the primary safety end points. The primary efficacy end point was chronic HCV infection, defined as persistent viremia for 6 months. RESULTS: A total of 548 participants underwent randomization, with 274 assigned to each group. There was no significant difference in the incidence of chronic HCV infection between the groups. In the per-protocol population, chronic HCV infection developed in 14 participants in each group (hazard ratio [vaccine vs. placebo], 1.53; 95% confidence interval [CI], 0.66 to 3.55; vaccine efficacy, −53%; 95% CI, −255 to 34). In the modified intention-to-treat population, chronic HCV infection developed in 19 participants in the vaccine group and 17 in placebo group (hazard ratio, 1.66; 95% CI, 0.79 to 3.50; vaccine efficacy, −66%; 95% CI, −250 to 21). The geometric mean peak HCV RNA level after infection differed between the vaccine group and the placebo group (152.51×10(3) IU per milliliter and 1804.93×10(3) IU per milliliter, respectively). T-cell responses to HCV were detected in 78% of the participants in the vaccine group. The percentages of participants with serious adverse events were similar in the two groups. CONCLUSIONS: In this trial, the HCV vaccine regimen did not cause serious adverse events, produced HCV-specific T-cell responses, and lowered the peak HCV RNA level, but it did not prevent chronic HCV infection. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT01436357.)

A 32-year old man presented with blurry vision, headache and vertigo. MRI revealed obstructive hydrocephalus from a hypointense lesion spanning the quadrigeminal cistern to the mesial temporal lobe, with restriction on DWI imaging suggesting an epidermoid cyst. The paramedian supracerebellar transtentorial approach was selected, and the procedure was performed in the sitting position. Gross total resection was achieved with punctate residual left on the posterior cerebral artery due to significant adherence. The patient remained neurologically stable postoperatively with a brief course of Parinaud’s syndrome. Two years post-operatively, imaging revealed significant tumor regrowth and he underwent reoperation through the same approach.

To provide the status of women neurosurgeons (WNS) in academic faculty and/or leadership positions in neurosurgery in the United States.Neurosurgery academic programs were defined as having an Accreditation Council for Graduate Medical Education (ACGME) neurosurgery residency program (NSRP). Using a Google search, gender, academic rank, postgraduate degrees, academic and clinical titles, and subspecialty were recorded for each neurosurgery faculty. Officer gender was recorded for the top 7 neurosurgery U.S. organizations, 7 subspecialty sections, and 50 state neurosurgical societies.WNS were faculty at 77% (89/115) of ACGME NSRPs and constituted 10% of the workforce (186/1773). WNS residents were in 92% of ACGME NSRPs and constituted 19% of the workforce (293/1515). Two NSRPs (8%) had neither WNS faculty nor WNS residents. Of NSRPs without WNS faculty, 52% (13/25) had a faculty size10. WNS accounted for 3% of NSRP chair positions. Academic rank of WNS faculty was lower than academic rank of men neurosurgeons faculty (P0.05). WNS faculty had a higher number of postgraduate degrees (P0.05). Pediatrics was the most common subspecialty (30%) among WNS. Over time, WNS held 1% of the leadership positions within the top 7 U.S. neurosurgery organizations and 7% within the 7 subspecialty sections. Over the past 20 years, 28% (14/50) of U.S. state neurosurgical societies had WNS serve as president.In 2020, the gender gap for U.S. WNS faculty and residents still exists. By providing informed benchmarks, our study might help neurosurgery organizations, medical school leadership, hiring committees, editors, and conference speakers to plan their next steps.

Posterior fossa dural arteriovenous fistulas (dAVFs) are rare vascular lesions with variable risk of hemorrhage, mostly depending on the pattern of the venous drainage. While endovascular embolization is the mainstay treatment for most dAVFs, some posterior fossa lesions require a multidisciplinary approach including surgery. The goal of our study was to examine the outcome of an interdisciplinary treatment for posterior fossa dAVFs.A retrospective review of patients treated for posterior fossa dAVFs was conducted.A total of 28 patients with a mean age of 57.8 years were included. Patients presented with a Cognard grade I in 2 (7%), II a in 5 (18 %), II b in 7 (25%), II a + b in 5 (18%), III in 3 (11%), and IV in 6 (21%) cases. Hemorrhage was the initial presentation in 2 (22%) patients with Cognard grade IV, in 3 with Cognard grade III (33%), in 1 (11%) with Cognard II a + b, and 3 (33%) with Cognard II b. A complete angiographic cure was achieved in 24 (86%) patients-after a single-session embolization in 16 (57%) patients, multiple embolization sessions in 2 (7%), a multimodal treatment with embolization and surgical disconnection in 3 (11%), and with an upfront surgery in 3 (11%). Complete long-term obliteration was demonstrated in 18/22 (82%) at the mean follow-up of 17 months. Fistulas were converted into asymptomatic Cognard I lesion in 4 (14%) patients.Posterior fossa dAVFs represent a challenging vascular pathology; however, despite their complexity, an interdisciplinary treatment can achieve high rates of angiographic and symptomatic cure with low morbidity and mortality rates. Long-term surveillance is warranted as late recurrences may occur.

Giant and large pituitary adenomas (PA) constitute a specific subset of PAs, with gross total resection (GTR) rates frequently not exceeding 50%. Both an anatomical inaccessibility and an inadequate tumor visualization are thought to play a role. This study analyzes risk factors for postoperative residuals after endoscopic transsphenoidal pituitary surgery for large and giant pituitary adenomas. A retrospective analysis of patients with giant and large PA operated between 2015 and 2018 was performed. Forty patients (13 females, 27 males) were included in the analysis (30 large and 10 giant PAs). The mean MRI follow-up time was 5.9 ± 6.54 months. Overall, GTR was achieved in 29 patients (72.5%), subtotal resection in 9 (22.5%), and the inconclusive result was in 2 (5%). Unexpected residuals represented 7 (77.7%) of all 9 residual tumors. The most frequent intraoperative factor associated with unexpected residual tumors was improper identification of residual tumor due to obstruction of view in 2 (28.5%) cases and inability to distinguish normal tissue from tumor in the other two (28.5%). Sub-analysis based on tumor size revealed that with large PAs, GTR was achieved in 25 (83.3%), STR in 4 (13.3%), and inconclusive in 1 (3.3%) patient. In patients with giant PAs, GTR was achieved in 4 (40%), STR in 5 (50%), and inconclusive in 1 (10%). Analysis of preoperative factors showed a significant association of residual tumors with larger suprasellar AP distance (p = 0.041), retrosellar extension (p = 0.007), and higher Zurich Score (p = 0.029). Large and giant PAs are challenging lesions with high subtotal resection rates. Suprasellar AP distance, retrosellar extension, and higher Zurich Score seem to be significant predictors of degree of resection in these tumors. Improving the intraoperative ability to distinguish tumor from a normal tissue might further decrease the number of unexpected residuals.

Neurophysiological monitoring is advocated for the prevention of neurological sequelae secondary to the clipping of an aneurysm involved in posterior circulation. Unfortunately, there is a paucity in the literature regarding what neurophysiological monitoring techniques are best employed. The authors here present two cases where multimodal neuromonitoring techniques were used during the clippings of two posterior inferior cerebellar artery (PICA) aneurysms. There is increased neurologic morbidity associated with PICA aneurysm clippings, as a number of eloquent structures live in close proximity to the PICA. The application of a multimodal neuromonitoring paradigm may reduce a poor neurological outcome.

Introduction. Young adults who inject drugs and live in rural communities are at high risk for hepatitis C virus (HCV) infection. Recent changes in HCV treatment must be communicated within these communities to improve access to care and reduce HCV transmission. Methods. Field workers in the ¡VÁLE! Hepatitis Treatment and Integrated Prevention Services study identified frequently asked questions (FAQs) posed by young-adult participants at high risk for HCV during screening and educational sessions. From 2016 to 2018, 183 young adults (44.3% women; 85.8% Latino/a) younger than 30 years who inject drugs and reside in Rio Arriba or Doña Ana counties in New Mexico were enrolled. The research team compiled deidentified questions during field enrollments. Results. FAQs were reviewed and categorized into four major domains, including risk/prevention, screening, treatment, and reinfection. FAQs were addressed by a team of medical and public health professionals, using the most current research and recommendations. Conclusions. These FAQs address important gaps in HCV knowledge among young adults who are at high risk for infection. The FAQs also highlight the importance of risk reduction counseling provided by frontline public health providers as well as access to safe and effective HCV treatments for young adults who inject drugs.

High-risk drinking (HRD) is a public health priority on college campuses in order to decrease harm to individuals who engage in HRD, as well as others in their presence. We posit an underexplored impact of campus HRD culture: the exposure of marginalized students to instances of bias perpetrated by those under the influence. Therefore, our focus on the reduction of HRD is not just about the health of drinkers but is also about the dynamics of interpersonal factors and community-level factors that can be upstream determinants of chronic stress and illness, particularly for marginalized college students. We argue that more attention should be paid to the intersection of HRD and intersections with social justice violations. Furthermore, we propose a model based on existing research that connects HRD with incidents of bias that increase stress, thereby negatively impacting well-being and increasing risk for chronic mental and physical illness. We ask our colleagues to incorporate these effects into th...

Quantifying the relationship between form and function can inform use of morphology as a surrogate for ecology. How the strength of this relationship varies continentally can inform understanding of evolutionary radiations; for example, does the relationship break down when certain lineages invade and diversify in novel habitats? The 75 species of Australian honeyeaters (Meliphagidae) are morphologically and ecologically diverse, with species feeding on nectar, insects, fruit, and other resources. We investigated Meliphagidae ecomorphology and community structure by (1) quantifying the concordance between morphology and ecology (foraging behavior), (2) estimating rates of trait evolution in relation to the packing of ecological space, and (3) comparing phylogenetic and trait community structure across the broad environmental gradients of the continent. We found that morphology explained 37% of the variance in ecology (and 62% vice versa), and we uncovered well-known bivariate relationships among the multivariate ecomorphological data. Ecological trait diversity declined less rapidly than phylogenetic diversity along a gradient of decreasing precipitation. We employ a new method (trait fields) and extend another (phylogenetic fields) to show that while species in phylogenetically clustered, arid-environment assemblages are similar morphologically, they are as varied in foraging behavior as those from more diverse assemblages. Thus, although closely related and similar morphologically, these arid-adapted species have diverged in ecological space to a similar degree as their mesic counterparts.

Endovascular and surgical techniques are conventional options for treating intracranial aneurysms, but criteria for selecting an optimal approach for individual patients remain variable across practitioners and institutions. While endovascular and surgical approaches are generally used alone, both modalities combined in single patients can produce efficacious outcomes. The aim of this study was to evaluate outcomes of combined, concomitant endovascular and surgical modalities in the treatment of multiple and/or complex aneurysms in single patients. Indications, sequencing rationale, and categorization for multimodality treatments are reviewed. All intracranial aneurysms treated at our institution from 2004 to 2014 were reviewed. Single patients who had undergone concomitant endovascular and surgical treatments were eligible for participation in our study. Demographic data and clinical presentation parameters, including location, size, and morphological features of lesions, treatment sequencing, and outcomes were recorded. Our cohort consisted of 27 patients with 57 aneurysms who received concomitant endovascular and surgical treatment of their aneurysm(s). One patient arrived to us after he had an aneurysm clipped at an outside institution and then required treatment for a contralateral ruptured aneurysm. 66.7% of patients were diagnosed with subarachnoid hemorrhage. These were subdivided according to therapeutic approach: clipping and coiling (CL+CO), clipping and stenting (CL+ST), bypass and endovascular parent vessel occlusion (PVO) (BY+PVO), attempted clipping then stenting, and bypass followed by stenting. Glasgow Outcome Scale was as follows: CL-CO-Multiple, 4.17 (five in unruptured patients, 3.75 in ruptured); CO-CL-Multiple, five (all patients had a ruptured aneurysm); CL-CO-Single, three (all patients had a ruptured aneurysm); CO-CL-Single, five (all patients had a ruptured aneurysm). No patients suffered a new neurological deficit as a result of treatment. A total of two mortalities were documented. Concomitant, mutimodality endovascular and surgical therapy may offer a safe and potentially more effective paradigm than single modality approaches for the management of multiple, complex, or "failed" aneurysm treatments in selected patients.

This paper demonstrates that environment-conscious consumers have lower gasoline retail (tax-exclusive) price and excise tax elasticities, suggesting that they are less sensitive to changes in prices and taxes than their less environmental counterparts. These results on an American state-year dataset are robust to the use of two environmental proxies and to the instrumentation of gasoline retail prices. These findings support the existence of heterogeneous environmental preferences by demonstrating that certain consumers incorporate environmental ideology into their utility functions distinctly from income considerations. The implication that environmental preferences contribute to differential responsiveness to pecuniary signals has repercussions for the forecasting of consumer behavior and for the ease of implementation of environmental policy.

This paper makes three contributions to the literature on private provision of public goods. First, we identify limitations of the frequently used specification test that distinguishes between the standard models of pure and impure altruism based on the extent of crowding out. While the literature takes as given the result that crowding out should be less with impure altruism compared with pure altruism, we show that, in general, it can be either more or less. Second, we propose a more general test based on the presence of crowding in, rather than the extent of crowding out. Third, we provide empirical evidence. Using a unique panel data set on volunteerism in U.S. National Parks, we estimate the causal effect of changes in public funding within parks on the amount of within-park volunteerism. The overall finding is that each additional dollar of public expenditure crowds in 27 cents worth of volunteerism on average. We show how the estimates of crowding in, along with heterogeneity based on park and volunteer hour types, are theoretically consistent with the mainstay model of impure altruism.

Retrochiasmatic craniopharyngiomas are difficult to treat due to their close proximity to critical neurovascular structures. Several surgical approaches with distinct advantages and limitations have been described to access these tumors, including extended transnasal endoscopic approach (ETEA), subtemporal, translamina terminalis, and transpetrosal approach.1-3 We present a 51-yr-old male with a large retrochiasmatic craniopharyngioma extending into the third ventricle, causing obstructive hydrocephalus. Preoperative magnetic resonance imaging (MRI) showed a tumor cyst abutting the fornices expanding the space between two internal cerebral veins (ICV). After surgical consent, we decided to take advantage of this corridor to approach the tumor in its long axis. Surgical goal was to achieve cyst decompression with "safe maximal" resection of the solid component at last to preserve the pituitary function. Though the long axis of the tumor could be approached using ETEA, we preferred this approach in view of cyst decompression early in the surgery while completely avoiding risks such as cerebrospinal fluid (CSF) rhinorrhea, internal carotid artery (ICA) injury, and sinonasal complications. We utilized a 3-dimensional 4 K exoscope, which provides an excellent ergonomic position, and a high-resolution immersive view compared to a microscope or endoscope. Cyst decompression and near-total resection of the solid component was achieved. Postoperatively, his headaches improved and he was neurologically intact with intact neuroendocrine function. Approach-related risks may include but not limited to hemorrhage due to the rupture of venous sinuses or ICV, stalk or hypothalamus injury, and memory disturbances due to forniceal injury. To conclude, the transcallosal, interforniceal approach to retrochiasmatic craniopharyngiomas may provide a safe surgical corridor in select cases. Patient consented to the proposed procedure. All radiological images have been anonymized. IRB/ethics committee approval was not required.

BACKGROUND: Although people who inject drugs (PWID) having the highest incidence and prevalence of hepatitis C virus (HCV) in the US, HCV treatment is rarely provided to PWID due to assumptions about poor adherence and reinfection risk. As direct-acting antiviral agents (DAAs) have achieved sustained virologic response (SVR) rates of 95% or more, evidence-based strategies are urgently needed to demonstrate real-world effectiveness in marginalized patient populations such as PWID. The objectives of this study are: 1) to determine whether either of two patient-centered treatment models - patient navigation (PN) or modified directly observed therapy (mDOT) - results in more forward movement along the HCV care cascade including treatment initiation, adherence, and SVR; 2) using quantitative and qualitative methods, to understand factors associated with lack of treatment uptake, poor adherence (< 80%), failure to achieve SVR, DAA resistance, and HCV reinfection. METHODS: The HERO study is a multi-site, pragmatic randomized clinical trial conducted in eight states where 754 HCV-infected PWID were randomly assigned to either PN or mDOT. CONCLUSIONS: This study addresses an urgent need for timely and accurate information on optimal models of care to promote HCV treatment initiation, adherence, treatment completion and SVR among PWID, as well as rates and factors associated with reinfection and resistance after treatment. This clinical trial has the potential to provide valuable information on how to reduce the burden of the HCV epidemic in PWID.

This paper studies social welfare in markets for natural disaster insurance. I quantify frictions in uptake, test for adverse selection, and estimate the welfare effects of proposed policy reforms by developing a model of natural disaster insurance markets and compiling new data. The paper has three main findings. First, willingness to pay for natural disaster insurance is remarkably low. In the high-risk flood zones throughout all U.S. Atlantic and Gulf Coast states, fewer than 60% of homeowners purchase flood insurance even though subsidized premia are only two-thirds of their own expected payouts. Second, homeowners select into insurance based on observable differences in houses' defensive investments against natural disasters (i.e., adaptation), but not on private information about risk. Exploiting house-level variation in flood insurance prices and construction codes reveals that requirements to elevate newly constructed homes reduce insurer costs by 31% and insurance demand by 25%. Asymmetric information between homeowners and insurers, however, does not affect average payouts. Third, ignoring how frictions, such as risk misperception, distort demand understates the welfare cost of currently proposed price increases and changes the sign of the predicted welfare effect. In the presence of such frictions, enforcing a natural disaster insurance mandate increases social welfare.

Aims We assessed prevalence and correlates for hepatitis C virus (HCV) infection in young adult people who inject drugs (PWID) in rural New Mexico, where opioid use has been historically problematic. Methods Participants were 18–29 years old with self-reported injection drug use in the past 90 days. We conducted testing for HCV antibodies (anti-HCV) and HCV ribonucleic acid (RNA) and assessed sociodemographic and risk exposures. We provided counseling and referrals to prevention services and drug treatment. We estimated prevalence ratios (PR) to assess bivariate associations with HCV infection; and adjusted PRs using modified Poisson regression methods. Results Among 256 participants tested for anti-HCV, 156 (60.9 %) had been exposed (anti-HCV positive), and of 230 tested for both anti-HCV and HCV RNA, 103 (44.8 %) had current infection (RNA-positive). The majority (87.6 %) of participants were Hispanic. Almost all (96.1 %) had ever injected heroin; 52.4 % and 52.0 % had ever injected methamphetamine or cocaine, respectively. Polysubstance injecting (heroin and any other drug) was associated with significantly higher prevalence of HCV infection (76.0 %) compared to injecting only heroin (24.0 %) (PR: 3.17 (95 % CI:1.93, 5.23)). Years of injecting, history of non-fatal opioid-involved overdose, polysubstance injecting, and stable housing were independently associated with HCV infection. Conclusions HCV is highly prevalent among young adult PWID in rural NM. The high reported prevalence of polysubstance injecting and its association with HCV infection should be considered in prevention planning.

INTRODUCTION: The anti-PD-1 monoclonal antibody nivolumab, used in metastatic melanoma, renal carcinoma, and advanced non-small cell lung cancer, may be used off-label in some PD-L1 positivite tumors. We report the first use (to our knowledge) of nivolumab in metastatic carcinoma of unknown primary with hepatoid features, with subsequent loss of PD-L1 expression on the tumor. CASE PRESENTATION: A 62-year old man complained of worsening back and right thigh pain. X-rays revealed an L3 compression fracture, which was managed non-operatively. He developed worsening right hip pain. Imaging revealed a right iliac mass, associated pathologic fracture, and multiple osteoblastic and osteolytic metastases. RESULTS: Iliac mass biopsy showed cords and nests of malignant epithelial cells with abundant eosinophilic cytoplasm, irregular nuclear contours, and prominent nucleoli. HepPar, Cam5.2, and PAX-8 (focal) immunohistochemical stains were positive, suggesting hepatic carcinoma. PD-L1 positivity was high (> 25% but < 50%). Genomic sequencing showed NF2, MLL2, and SETD2 mutations. Workup showed no hepatic involvement, so stage IV hepatoid carcinoma of unknown primary was diagnosed. TREATMENT: Several bony lesions were radiated. Nivolumab (240 mg every 2 weeks) and denosumab (monthly) were started. PROGRESSION: Seven months later he developed left ptosis and proptosis from a sellar/left cavernous sinus mass. Histology was similar to the previous iliac biopsy, but with more aggressive features (mitoses, atypical nuclei). Cam5.2 and synaptophysin immunohistochemical stains were positive; PD-L1 expression was

Malignant gliomas, including glioblastomas (GBMs) and anaplastic astrocytomas (AAs), remain difficult to treat. Overall prognosis for patients harboring these tumors is poor despite maximal surgical resection with appropriate chemotherapy and radiation. Here we outline several novel treatment modalities for focal control of malignant gliomas. The first set of therapies described rely on bypassing the blood brain barrier (BBB) to better deliver chemotherapeutics directly to the tumor and tumor cells infiltrating into the brain parenchyma. These include convection-enhanced drug delivery, intra-arterial (IA) chemotherapy, focused ultrasound, and laser interstitial thermal therapy. Another modality that has shown promising tumor control is tumor treatment fields therapy, which disrupts tumor mitosis and has increased survival in some studies. We also discuss the challenges associated with these treatments and examine the future of these and other glioma management strategies.

How do children acquire exact meanings for number words like three or forty-seven? In recent years, a lively debate has probed the cognitive systems that support learning, with some arguing that an evolutionarily ancient “approximate number system” drives early number word meanings, and others arguing that learning is supported chiefly by representations of small sets of discrete individuals. This debate has centered around findings generated by Wynn’s (1990, 1992) Give-a-Number task, which she used to categorize children into discrete “knower level” stages. Early reports confirmed Wynn’s analysis, and took these stages to support the “small sets” hypothesis. However, more recent studies have disputed this analysis, and have argued that Give-a-Number data reveal a strong role for approximate number representations. In the present study, we use previously collected Give-a-Number data to replicate the analyses of these past studies, and to show that differences between past studies are due to assumptions made in analyses, rather than to differences in data themselves. We also show how Give-a-Number data violate the assumptions of parametric tests used in past studies. Based on simple non-parametric tests and model simulations, we conclude that (1) before children learn exact meanings for words like one, two, three, and four, they first acquire noisy preliminary meanings for these words, (2) there is no reliable evidence of preliminary meanings for larger meanings, and (3) Give-a- Number cannot be used to readily identify signatures of the approximate number system.

Previous accounts of how people develop expertise have focused on how deliberate practice transforms the cognitive and perceptual representations and processes that give rise to expertise. However, the likelihood of developing expertise with a particular tool may also depend on the degree to which that tool fits pre-existing perceptual and cognitive abilities. The present studies explored whether the abacus – a descendent of the first human computing devices – may have evolved to exploit general biases in human visual attention, or whether developing expertise with the abacus requires learning special strategies for allocating visual attention to the abacus. To address this question, we administered a series of visual search tasks to abacus experts and subjects who had little to no abacus experience, in which search targets and distractors were overlaid atop abacus “beads.” Across three studies, we found that both experts and naïve subjects were faster to detect targets in semantically-relevant components of the abacus, suggesting that abacus training is not required to exhibit attentional biases toward these components of the abacus. This finding suggests that the attentional biases that scaffold numerical processing of the abacus may emerge from general properties of visual attention that are exploited by the design of the abacus itself.

Background The development of a safe and effective vaccine to prevent chronic hepatitis C virus (HCV) infection is a critical component of elimination efforts, providing the rationale for the first HCV vaccine efficacy trial. Methods In a randomized, multicenter, double-blind, placebo-controlled efficacy trial (NCT01436357), we evaluated a recombinant chimpanzee adenovirus 3 vector vaccine prime followed by a recombinant modified vaccinia Ankara boost, both encoding nonstructural proteins of HCV. HCV-uninfected adults 18–45 years old at-risk for HCV infection due to injection drug use were randomized to receive the prime-boost regimen or placebo at Days 0 and 56. Trial participants were monitored for vaccine reactogenicity, adverse events, and HCV viremia. Vaccine safety, immunogenicity, and efficacy against progression to chronic HCV infection were assessed. Results A total of 455 subjects received the prime-boost regimen or two doses of placebo, with 202 and 199 in the respective groups included in the according-to-protocol efficacy cohort. Overall incidence of infection was 14.1 infections per 100 person-years. There were no differences in development of chronic infection between vaccine and placebo arms, with 14 chronically infected subjects in each group. Specifically, the vaccine efficacy in preventing chronic infection was −0.53 (95% confidence interval [CI], −2.5 to 0.34). Of vaccinated subjects, 78% generated T-cell responses to ≥1 vaccine-encoded HCV antigens. The vaccine was generally safe and well tolerated with no serious vaccine-related adverse events. There were more solicited reports of adverse events after either injection in the vaccine group (81%) than in the placebo group (59%), with the difference mainly due to injection-site reactions. Serious adverse events and deaths occurred with similar frequencies in the two groups. Conclusion A randomized, placebo controlled, Phase I/II trial of a prime-boost vaccine to prevent chronic HCV infection was completed in an at-risk population, demonstrating the feasibility of conducting rigorous vaccine research in people who inject drugs. The regimen elicited robust immune responses without evident safety concerns, but did not provide protection against chronic HCV infection. Disclosures Ventzislav Vassilev, PhD, GlaxoSmithKlein Vaccines (Employee), Lan Lin, MD, GlaxoSmithKlein Vaccines (Employee), Alfredo Nicosia, PhD, ReiThera (Employee, Shareholder), Antonella Folgori, PhD, ReiThera (Employee), ReiThera (Employee, Shareholder. Other Authors: No reported disclosures.

Purpose of Review There is still substantial controversy surrounding the utility of decompressive craniectomy (DC) in patients with traumatic brain injury (TBI). Some surgeons readily perform these operations, while others are more hesitant due to concerns about patient outcomes in severe TBI.

Previous studies report that children use color words haphazardly before acquiring conventional, adult-like meanings. The most common explanation for this is that children do not abstract color as a domain of linguistic meaning until several months after they begin producing color words, resulting in a stage during which they produce but do not comprehend color words. Contrary to this account, the current study provides converging evidence from multiple measures that toddlers often acquire partial but systematic color word meanings before production, although adult meanings are acquired much later. Also, we found that whereas children’s interpretation of color words is relatively conservative before the onset of color word production, their meanings become broader and overextended upon the onset of production. These data support the idea that inductive processes of category formation, rather than problems abstracting color, explain the delay between children’s first production of color words and mastery of adult meanings.

Optical entanglement — a key requirement for many quantum communication protocols — is typically formed between two distinct beams, requiring repeated combination of complex resources, which becomes increasingly difficult as the number of entangled information channels increases. Here entanglement between two spatial modes within one beam is demonstrated.

To determine whether methadone maintenance alters intrapartum or postpartum pain or medication requirements.Sixty-eight patients treated with methadone for opiate dependence during pregnancy (vaginal n=35; cesarean n=33) were matched retrospectively to control women. Analgesic medication and pain scores (0-10) were extracted from the medical record. The primary endpoint was opiate use postpartum (oxycodone equivalents). The secondary endpoints were pain scores and intrapartum analgesia.There were no differences in intrapartum pain or analgesia. After vaginal birth, methadone-maintained women experienced increased pain (methadone, 2.7 [1.9-5.0]; control, 1.4 [0.5-3.0], P=.001) but no increase in opiate use ([mean+/-standard deviation] methadone 12.7+/-32.1; control 6.8+/-12.7 mg/24 h, P=.33); after cesarean delivery both pain (methadone, 5.3 [4.1-6.0]; control, 3.0 [2.2-3.9], P=.001) and opiate use (methadone, 91.6+/-51.8; control, 54.0+/-18.6 mg/24 h, P=.001) increased.Methadone-maintained women have similar analgesic needs and response during labor, but require 70% more opiate analgesic after cesarean delivery.II.

Terror medicine, a field related to emergency and disaster medicine, focuses on medical issues ranging from preparedness to psychological manifestations specifically associated with terrorist attacks. Calls to teach aspects of the subject in American medical schools surged after the 2001 jetliner and anthrax attacks. Although the threat of terrorism persists, terror medicine is still addressed erratically if at all in most medical schools. This paper suggests a template for incorporating the subject throughout a 4-year medical curriculum. The instructional framework culminates in a short course for fourth year students, such as one recently introduced at Rutgers New Jersey Medical School, Newark, NJ, USA. The proposed 4-year Rutgers curriculum serves as a model that could assist other medical schools contemplating the inclusion of terror medicine in pre-clerkship and clerkship training.