Analysis of the Sonopet Ultrasonic Bone Aspirator to Traditional Instrumentation for Endoscopic Suturectomy for Craniosynostosis.

OBJECTIVE: The goal of endoscopic treatment for craniosynostosis is to remove the fused suture and achieve calvarial remodeling with external orthosis. To reduce the need for secondary surgery and to minimize blood loss, instruments that maximize bone removal while minimizing blood loss and risk of dural injury are evolving. The authors therefore assess the safety and efficacy of the Sonopet Ultrasonic Bone Aspirator (UBA) (Stryker, Kalamazoo, MI) for endoscopic suturectomy compared to traditional instrumentation at our institution. METHODS: Retrospective chart review of consecutive endoscopic suturectomies performed from 2011 to 2019 at Weill Cornell Medical Center was conducted, including demographics, cephalic index, surgical indications, operative time, cosmetic and functional results, complications, estimated blood loss (EBL), re-operation rate, length of stay, and length of helmet therapy. These variables were then compared between the Sonopet and non-Sonopet cohorts. RESULTS: Of the 60 patients who underwent endoscopic suturectomy, 16 cases (26.7%) utilized the Sonopet. Mean operative time was 2.8 ±â€Š0.4 hours in the Sonopet group, compared to 3.2 ±â€Š1.2 hours (P = 0.05) without the Sonopet. EBL was 17.8 ±â€Š23.9 cc versus 34.7 ±â€Š75.5 cc (P = 0.20) with versus without the Sonopet respectively. Length of stay and duration of helmet therapy were similar in both groups, ranging from 1 to 3 days (P = 0.68) and 7.25 to 12 months (P = 0.30) respectively. There were no reoperations in the Sonopet group with a mean follow up of 9.18 months. There were 3 reoperations in the non-Sonopet group with a mean follow up of 11.3 months. Among the cases utilizing the Sonopet, 13 (81%) were metopic and three (19%) were coronal synostoses. Of the non-Sonopet cases, 27 (61%) were sagittal, 8 (18%) were metopic, 7 (16%) were coronal, and 2 (5%) were lambdoid synostoses. CONCLUSIONS: The use of the Sonopet resulted in a mean decrease in operative time at our institution (P = 0.18). Lower EBL and reoperation rates with comparable LOS and helmet therapy duration were also seen. This modality should be considered a safe and effective adjunct in appropriate endoscopic craniosynostosis cases.

Surgical Management of Complex Syndromic Craniosynostosis: Experience With a Rare Genetic Variant.

Patients with syndromic craniosynostosis (CS) can present with both intracranial and extracranial manifestations. Extracranial features include proptosis, exorbitism, and midface hypoplasia. Intracranial manifestations can include elevated intracranial pressure (ICP), brainstem compression, foramen magnum stenosis or jugular foramen hypoplasia with resultant venous hypertension and anomalous drainage. While fronto-orbital advancement, cranial vault remodeling, and posterior fossa decompression are standard surgical approaches to normalizing orbito-cranial volume and morphology, associated hydrocephalus, anomalous venous drainage, and tonsillar herniation often affect the timing, safety, and selection of corrective interventions. The surgical decision-making to circumvent venous emissaries, effectively time treatment of hydrocephalus, and address posterior versus anterior pathology primarily has not been widely described in the literature, and is important in the development of guidelines in these complex cases. In this report, we describe the surgical management of a patient with Jackson-Weiss syndrome presenting with delayed, but rapidly progressive bilateral lambdoid CS, severe proptosis, midface hypoplasia, elevated ICP, hydrocephalus, tonsillar ectopia, and severe venous hypertension with anomalous drainage. We review the literature related to management of complex synostosis and present our surgical decision-making in the setting of complex syndromic synostosis to aid in the formation of guidelines toward approaching these cases.

Impact of a Multidisciplinary Craniofacial Clinic for Patients With Craniofacial Syndromes on Patient Satisfaction and Outcome.

OBJECTIVE: Multidisciplinary clinics are becoming widely utilized. Given the number of patients with craniofacial syndromes evaluated at our institution, and the burden of assessment by multiple subspecialists, we created an American Cleft Palate-Craniofacial Association-certified Craniofacial Multidisciplinary Clinic (CMC) composed of a nurse practitioner, neurosurgeon, plastic surgeon, otolaryngologist, oromaxillofacial surgeon, geneticist, pulmonologist, occupational therapist, dentist, and child life specialist to improve patient experience, lessen the burden of assessment, decrease time to surgery, and improve patients' understanding of the diagnosis and treatment plan specifically for patients with complex craniofacial syndromes. We reviewed the impact of this clinic after 1 year of implementation. DESIGN: Retrospective review was performed to identify patients with craniofacial syndromic diagnoses seen by the neurosurgery department before and after implementation of the CMC from February 2017 to present. SETTING: The CMC is an outpatient clinic based in a tertiary care academic institution. PATIENTS: Chart review was performed to identify demographic, diagnostic, clinical, and treatment data. We assessed clinic experience, and the impact on quality of clinical and surgical care was assessed via survey. We compared this cohort to patients with similar craniofacial syndromes treated prior to the CMC. Thirty patients seen at the CMC were identified, and data from a comparable cohort of 30 patients seen prior to the clinic's inception was reviewed. RESULTS: Our CMC survey response rate was 67% (n = 20/30) for the CMC patients. Second opinions sought by parents prior to CMC was higher (mean = 0.85, range: 0-3) than for patients seen at the CMC (mean = 0.16, range: 0-1). Mean time to surgery before the CMC was 10.1 months (range: 1-15) compared to 4 months (range: 3-5) after implementation. Parents agreed that they felt well-informed about their diagnosis (n = 18/20, 90%), and that the presence of a plastic surgeon (19/20, 95%) and a nurse practitioner (17/20, 85%) were valuable in coordination of their care. Following surgery, 76% (n = 13/17) of patients who received surgery were happy with the outcome, 76% (n = 13/17) were happy with the appearance of the scar, and 95% (n = 19/20) would recommend the CMC to others. CONCLUSION: Multidisciplinary evaluation of patients with complex craniofacial conditions provides comprehensive, efficient, and effective care, as well as improved parent satisfaction and knowledge base.

Looking into the One-way Mirror: A Pilot Study on the Impact of Reflecting Teams on Family Members.

Reflecting Teams (RTs) are an internationally recognized clinical consultation methodology, first developed by Tom Andersen in 1985. Over the last three decades, family therapists around the world have used RTs to enhance treatment. However, this innovation to family therapy practice is not well-standardized nor evaluated. The pilot study described in this article is an attempt to expand on the previous studies on RTs, and quantitatively examines RTs conducted with family therapy participants at a university medical center psychiatric institute. Preliminary analyses indicate that after participating in a single RT, family members may feel more hopeful, believe they can better support each other in times of stress, have more confidence in working together, and resolve conflicts. Additionally, the analyses suggest that family members may feel better understood and have more ideas about how to have a conversation with their family members, even though, after the RT, they may not view their family differently. These preliminary results suggest that further studies should explore the influence of RTs on family functioning.

Los "equipos reflexivos" (Reflecting Teams, RTs) son una metodología de consulta clínica reconocida a nivel internacional que fue desarrollada por primera vez por Tom Andersen en 1985 (Andersen, 1992). Durante las últimas tres décadas, los terapeutas familiares de todo el mundo han usado los equipos reflexivos para optimizar el tratamiento (p. ej.: Brownlee, Vis, & McKenna, 2009; Höger, Temme, Reiter, & Steiner, 1994). Sin embargo, esta innovación en la práctica de terapia familiar no está bien estandarizada ni evaluada. El estudio piloto descrito en este artículo es un intento de ampliar estudios previos sobre los equipos reflexivos y de analizar cuantitativamente los equipos reflexivos implementados con los participantes de una terapia familiar en un instituto psiquiátrico y un centro médico universitario. Los análisis preliminares indican que después de participar en un solo equipo reflexivo, los familiares pueden sentirse más optimistas, creer que pueden apoyarse mejor mutuamente en momentos de estrés, tener más confianza en trabajar juntos y resolver conflictos. Los integrantes de la familia también pueden sentirse mejor comprendidos y tener más ideas acerca de cómo conversar con sus familiares. Sin embargo, después del equipo reflexivo, es posible que no vean a su familia de forma diferente. Estos resultados preliminares sugieren que otros estudios deberían analizar la influencia de los equipos reflexivos en el funcionamiento familiar.

The oral VEGF receptor tyrosine kinase inhibitor pazopanib in combination with the MEK inhibitor trametinib in advanced cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma is an aggressive malignancy with limited therapeutic options. MEK inhibition and antiangiogenic therapies have individually shown modest activity in advanced cholangiocarcinoma, whereas dual inhibition of these pathways has not been previously evaluated. We evaluated the safety and efficacy of combination therapy with the oral VEGF receptor tyrosine kinase inhibitor pazopanib plus the MEK inhibitor trametinib in patients with advanced cholangiocarcinoma. METHODS: In this open-label, multicentre, single-arm trial, adults with advanced unresectable cholangiocarcinoma received pazopanib 800 mg daily and trametinib 2 mg daily until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS) with secondary end points including overall survival (OS), response rate, and disease control rate (DCR). RESULTS: A total of 25 patients were enrolled and had received a median of 2 prior systemic therapies (range 1-7). Median PFS was 3.6 months (95% CI: 2.7-5.1) and the 4-month PFS was 40% (95% CI: 24.7-64.6%). There was a trend towards increased 4-month PFS as compared with the prespecified null hypothesised 4-month PFS of 25%, but this difference did not reach statistical significance (P=0.063). The median survival was 6.4 months (95% CI: 4.3-10.2). The objective response rate was 5% (95% CI: 0.13-24.9%) and the DCR was 75% (95% CI: 51%, 91%). Grade 3/4 adverse events attributable to study drugs were observed in 14 (56%) and included thrombocytopenia, abnormal liver enzymes, rash, and hypertension. CONCLUSIONS: Although the combination of pazopanib plus trametinib had acceptable toxicity with evidence of clinical activity, it did not achieve a statistically significant improvement in 4-month PFS over the prespecified null hypothesised 4-month PFS.

Entinostat, nivolumab and ipilimumab for women with advanced HER2-negative breast cancer: a phase Ib trial.

We report the results of 24 women, 50% (N = 12) with hormone receptor-positive breast cancer and 50% (N = 12) with advanced triple-negative breast cancer, treated with entinostat + nivolumab + ipilimumab from the dose escalation (N = 6) and expansion cohort (N = 18) of ETCTN-9844 ( NCT02453620 ). The primary endpoint was safety. Secondary endpoints were overall response rate, clinical benefit rate, progression-free survival and change in tumor CD8:FoxP3 ratio. There were no dose-limiting toxicities. Among evaluable participants (N = 20), the overall response rate was 25% (N = 5), with 40% (N = 4) in triple-negative breast cancer and 10% (N = 1) in hormone receptor-positive breast cancer. The clinical benefit rate was 40% (N = 8), and progression-free survival at 6 months was 50%. Exploratory analyses revealed that changes in myeloid cells may contribute to responses; however, no correlation was noted between changes in CD8:FoxP3 ratio, PD-L1 status and tumor mutational burden and response. These findings support further investigation of this treatment in a phase II trial.

Positional identification of variants of Adamts16 linked to inherited hypertension.

A previously reported blood pressure (BP) quantitative trait locus on rat Chromosome 1 was isolated in a short congenic segment spanning 804.6 kb. The 804.6 kb region contained only two genes, LOC306664 and LOC306665. LOC306664 is predicted to translate into A Disintegrin-like and Metalloproteinase with Thrombospondin Motifs-16 (Adamts16). LOC306665 is a novel gene. All predicted exons of both LOC306664 and LOC306665 were sequenced. Non-synonymous variants were identified in only one of these genes, LOC306664. These variants were naturally existing polymorphisms among inbred, outbred and wild rats. The full-length rat transcript of Adamts16 was detected in multiple tissues. Similar to ADAMTS16 in humans, expression of Adamts16 was prominent in the kidney. Renal transcriptome analysis suggested that a network of genes related to BP was differential between congenic and S rats. These genes were also differentially expressed between kidney cell lines with or without knock-down of Adamts16. Adamts16 is conserved between rats and humans. It is a candidate gene within the homologous region on human Chromosome 5, which is linked to systolic and diastolic BP in the Quebec Family Study. Multiple variants, including an Ala to Pro variant in codon 90 (rs2086310) of human ADAMTS16, were associated with human resting systolic BP (SBP). Replication study in GenNet confirmed the association of two variants of ADAMTS16 with SBP, including rs2086310. Overall, our report represents a high resolution positional cloning and translational study for Adamts16 as a candidate gene controlling BP.

Intraarterial delivery of bevacizumab and cetuximab utilizing blood-brain barrier disruption in children with high-grade glioma and diffuse intrinsic pontine glioma: results of a phase I trial.

OBJECTIVE: Delivery of drugs intraarterially to brain tumors has been demonstrated in adults. In this study, the authors initiated a phase I trial of superselective intraarterial cerebral infusion (SIACI) of bevacizumab and cetuximab in pediatric patients with refractory high-grade glioma (diffuse intrinsic pontine glioma [DIPG] and glioblastoma) to determine the safety and efficacy in this population. METHODS: SIACI was used to deliver mannitol (12.5 ml of 20% mannitol) to disrupt the blood-brain barrier (BBB), followed by bevacizumab (15 mg/kg) and cetuximab (200 mg/m2) to target VEGF and EGFR, respectively. Patients with brainstem tumors had a balloon inflated in the distal basilar artery during mannitol infusion. RESULTS: Thirteen patients were treated (10 with DIPG and 3 with high-grade glioma). Toxicities included grade I epistaxis (2 patients) and grade I rash (2 patients). There were no dose-limiting toxicities. Of the 10 symptomatic patients, 6 exhibited subjective improvement; 92% showed decreased enhancement on day 1 posttreatment MRI. Of 10 patients who underwent MRI at 1 month, 5 had progressive disease and 5 had stable disease on FLAIR, whereas contrast-enhanced scans demonstrated progressive disease in 4 patients, stable disease in 2, partial response in 2, and complete response in 1. The mean overall survival for the 10 DIPG patients was 519 days (17.3 months), with a mean posttreatment survival of 214.8 days (7.2 months). CONCLUSIONS: SIACI of bevacizumab and cetuximab was well tolerated in all 13 children. The authors' results demonstrate safety of this method and warrant further study to determine efficacy. As molecular targets are clarified, novel means of bypassing the BBB, such as intraarterial therapy and convection-enhanced delivery, become more critical. Clinical trial registration no.: NCT01884740 (clinicaltrials.gov).

Anti-roma Bias (Stereotypes, Prejudice, Behavioral Tendencies): A Network Approach Toward Attitude Strength.

The Roma have been and still are a target of prejudice, marginalization, and social exclusion across Europe, especially in East-Central European countries. This paper focuses on a set of stereotypical, emotional, and behavioral evaluative responses toward Roma people selected as representing the underlying components of anti-Roma bias. Employing network analysis, we investigated if attitude strength is associated with stronger connectivity in the networks of its constituent elements. The findings from representative surveys carried out in Hungary, Romania, Slovakia, France, and Ireland supported our assumption, as high attitude strength toward the Roma resulted in stronger connectivity in all pairs of high- versus low-attitude-strength networks. Our finding yields a solid theoretical framework for targeting the central variables-those with the strongest associations with other variables-as a potentially effective attitude change intervention strategy. Moreover, perceived threat to national identity, sympathy, and empathy were found to be the most central variables in the networks.

Phase I and Pharmacokinetic Study of Romidepsin in Patients with Cancer and Hepatic Dysfunction: A National Cancer Institute Organ Dysfunction Working Group Study.

PURPOSE: Romidepsin dosing recommendations for patients with malignancy and varying degrees of hepatic dysfunction was lacking at the time of regulatory approval for T-cell lymphoma. We conducted a multicenter phase I clinical trial (ETCTN-9008) via the NCI Organ Dysfunction Working Group to investigate safety, first cycle MTD, and pharmacokinetic profile of romidepsin in this setting. PATIENTS AND METHODS: Patients with select advanced solid tumors or hematologic malignancies were stratified according to hepatic function. Romidepsin was administered intravenously on days 1, 8, and 15 of a 28-day cycle and escalation followed a 3 + 3 design in moderate and severe impairment cohorts. Blood samples for detailed pharmacokinetic analyses were collected after the first dose. RESULTS: Thirty-one patients received one dose of romidepsin and were evaluable for pharmacokinetic analyses in normal (n = 12), mild (n = 8), moderate (n = 5), and severe (n = 6) cohorts. Adverse events across cohorts were similar, and dose-limiting toxicity occurred in two patients (mild and severe impairment cohorts). The MTD was not determined because the geometric mean AUC values of romidepsin in moderate (7 mg/m2) and severe (5 mg/m2) impairment cohort were 114% and 116% of the normal cohort (14 mg/m2). CONCLUSIONS: Data from the ETCTN-9008 trial led to changes in the romidepsin labeling to reflect starting dose adjustment for patients with cancer and moderate and severe hepatic impairment, with no adjustment for mild hepatic impairment.

Creating and testing regulatory focus messages to enhance medication adherence.

OBJECTIVES: Strategies were explored to improve patient adherence to cardioprotective medications by borrowing from a motivational framework used in psychology, regulatory focus theory. The current study is part of a larger randomized control trial and was aimed at understanding what written educational messages, based on patients' regulatory focus tendency, resonated with each individual as a potential reminder to take medications. This study was also aimed at understanding why messages resonated with the patients. METHODS: Twenty veterans were tested for regulatory fitand presented with messages dependent on focus tendency. In-person semi-structured interviews were conducted to collect feedback of messages. An iterative analysis drawing primarily on matrix and reflexive team analyses was conducted. RESULT: Six promotion and six prevention messages emerged, such as "team up with your provider to create a combination of medications to prevent illness" and "Live your best life - Take your medications". Five themes related to types of health messages that spoke to patients' regulatory fit were discovered: relatability; empowerment and control; philosophy on life; relationship with provider and medications; and vocabulary effect on the impact of messages. DISCUSSION: Motivational messages based on regulatory fit may be useful in improving patient medication adherence, leading to improved cardiovascular outcomes.

Impact of an advanced practice provider-directed plagiocephaly clinic for neurosurgical practices.

OBJECTIVE: In recent years, the Weill Cornell neurosurgical team noticed an increase in referrals for plagiocephaly, likely due to increased infant back-sleeping and awareness. A plagiocephaly clinic staffed by a nurse practitioner and a physician assistant was established in 2016 to meet this demand, and to decrease the nonsurgical case burden on neurosurgeons. The purpose of this study was to examine the impact of a clinic directed by advanced nonphysician practice providers (NPPs) on parental satisfaction and nonsurgical work hours for staff neurosurgeons. METHODS: Over a 1.5-year period (from January 1, 2016, to June 20, 2017), Likert scale-based surveys were administered to parents before and after their child's visit to the NPP-staffed clinic. Clinic hours were tracked to assess impact on the neurosurgeon's workload. RESULTS: All 185 patients seen in the plagiocephaly clinic over the 1.5-year period completed pre- and postvisit surveys. Parents all reported a significant reduction in their level of concern for their child's diagnosis after the evaluation, and 95.5% were "very likely" to recommend the clinic. All parents felt that there was an increase in their knowledge base after an appointment with an NPP. Additionally, over 1 year in the study, 170 visits to the NPP plagiocephaly clinic were recorded, resulting in 85 hours that neurosurgeons normally would have spent in the clinic that they now were able to spend in the operating room. CONCLUSIONS: This research provides evidence that an NPP-directed clinic can positively impact parental satisfaction and decrease nonsurgical case burden on neurosurgeons.

Developing a 3D composite training model for cranial remodeling.

OBJECTIVE: Craniosynostosis correction, including cranial vault remodeling, fronto-orbital advancement (FOA), and endoscopic suturectomy, requires practical experience with complex anatomy and tools. The infrequent exposure to complex neurosurgical procedures such as these during residency limits extraoperative training. Lack of cadaveric teaching tools given the pediatric nature of synostosis compounds this challenge. The authors sought to create lifelike 3D printed models based on actual cases of craniosynostosis in infants and incorporate them into a practical course for endoscopic and open correction. The authors hypothesized that this training tool would increase extraoperative facility and familiarity with cranial vault reconstruction to better prepare surgeons for in vivo procedures. METHODS: The authors utilized representative craniosynostosis patient scans to create 3D printed models of the calvaria, soft tissues, and cranial contents. Two annual courses implementing these models were held, and surveys were completed by participants (n = 18, 5 attending physicians, 4 fellows, 9 residents) on the day of the course. These participants were surveyed during the course and 1 year later to assess the impact of this training tool. A comparable cohort of trainees who did not participate in the course (n = 11) was also surveyed at the time of the 1-year follow-up to assess their preparation and confidence with performing craniosynostosis surgeries. RESULTS: An iterative process using multiple materials and the various printing parameters was used to create representative models. Participants performed all major surgical steps, and we quantified the fidelity and utility of the model through surveys. All attendees reported that the model was a valuable training tool for open reconstruction (n = 18/18 [100%]) and endoscopic suturectomy (n = 17/18 [94%]). In the first year, 83% of course participants (n = 14/17) agreed or strongly agreed that the skin and bone materials were realistic and appropriately detailed; the second year, 100% (n = 16/16) agreed or strongly agreed that the skin material was realistic and appropriately detailed, and 88% (n = 14/16) agreed or strongly agreed that the bone material was realistic and appropriately detailed. All participants responded that they would use the models for their own personal training and the training of residents and fellows in their programs. CONCLUSIONS: The authors have developed realistic 3D printed models of craniosynostosis including soft tissues that allow for surgical practice simulation. The use of these models in surgical simulation provides a level of preparedness that exceeds what currently exists through traditional resident training experience. Employing practical modules using such models as part of a standardized resident curriculum is a logical evolution in neurosurgical education and training.

A Phase I Trial of the VEGF Receptor Tyrosine Kinase Inhibitor Pazopanib in Combination with the MEK Inhibitor Trametinib in Advanced Solid Tumors and Differentiated Thyroid Cancers.

PURPOSE: Differentiated thyroid cancer (DTC) responds to VEGF receptor inhibitors. VEGF signals through RAS/RAF/MEK signaling. We evaluated the safety and efficacy of the VEGF receptor inhibitor pazopanib and MEK inhibitor trametinib in advanced solid tumors and DTC. PATIENTS AND METHODS: Patients with advanced solid tumors were enrolled in a phase I, multicenter trial with a DTC expansion cohort. Patients received pazopanib 400-800 mg and trametinib 1-2 mg daily. Efficacy in the expansion cohort was assessed with objective response (OR) at 6 months of treatment. RESULTS: Twenty-six patients were enrolled in five dose levels. MTD was not reached; the recommended phase II dose was pazopanib 800 mg orally and trametinib 2 mg orally every day. There was one dose-limiting toxicity on dose level 1 with grade 3 fatigue and muscle weakness. Common grade 3 adverse events were elevated transaminases (19%), diarrhea (15%), hypertension (12%), and fatigue (8%). Thirteen patients were enrolled in the DTC cohort; OR was 33% (95% confidence interval, 9.9, 65.1%) and median progression-free survival was 10.7 months. The cohort was terminated after planned interim analysis suggested insufficiently increased activity against the historical control of pazopanib alone. Reduction in tumor diameter negatively correlated with p-ERK change in tumor (Spearman ρ = -0.71; P = 0.05). NRAS mutation was associated with response (Fisher exact P = 0.008). CONCLUSIONS: Pazopanib + trametinib was tolerable at full single-agent doses with clinical activity in DTC but did not achieve the prespecified response rate target.

Replication of the Wellcome Trust genome-wide association study of essential hypertension: the Family Blood Pressure Program.

Essential hypertension is a principal cardiovascular risk factor whose origin remains unknown. Classical genetic studies have shown that blood pressure is at least partially heritable, opening a window to understanding the pathophysiology of essential hypertension in the human using modern genetic tools. The Wellcome Trust Case Control Consortium has recently published the results of screening the genomes of 2000 essential hypertension cases and 3000 controls using 500 000 genome-wide single nucleotide polymorphisms (SNPs). None of the variants proved to be genome-wide significant after correction for multiple tests but the most significantly associated SNPs (P<10(-5)) constitute a priority list that warrant follow-up in other studies. We describe here replication studies of the top six SNPs in subjects from the US National Heart, Lung, and Blood Institute funded Family Blood Pressure Program comprising 11 433 individuals recruited by hypertensive families. The results suggest that only one of the six SNPs might be associated with essential hypertension in Americans of European origin. This SNP shows a significant but opposite effect in Americans of Hispanic origin and no association in African Americans. The significance of the opposing effect estimates is unclear. No replication could be shown for hypertension status, but there are differences in study design. This attempted replication highlights that essential hypertension studies will require more comprehensive and larger genetic screens.

Development and Validation of the Transgender Inclusive Behavior Scale (TIBS).

Transgender-inclusive behaviors are actions and communication supporting transgender individuals. Examples include using language not reinforcing the gender binary, asking for and using correct pronouns, creation of spaces that welcome members of the transgender community, and acknowledging cisgender (non-transgender) privilege. A survey was developed measuring this behavior in individuals to examine the impact of transgender-inclusive behavior and the potential effect of interventions on promoting inclusive behavior. Data were collected utilizing an online survey (N = 1,051). The sample was split in half to run two sets of cases in a principal components analysis. Analysis of the full sample showed Cronbach's alpha to be .93 (n = 918). Findings suggest that the Transgender Inclusive Behavior Scale (TIBS) may be a useful instrument for identifying behaviors related to being inclusive of transgender individuals, groups, and communities. It may also be used to measure behavior change before and after transgender-specific educational and behavioral interventions.

Student veterans with posttraumatic stress symptoms: Perceived preferences for on-campus psychoeducation.

OBJECTIVE: This investigation aimed to better understand perceived barriers to academic success and preferences for a veteran-specific psychosocial course among veterans with symptoms of posttraumatic stress (PTS). METHOD: Ninety-three veterans participated in this investigation as part of a larger study examining psychosocial functioning among veterans with PTS symptoms. Participants completed a self-report survey focused on perceived barriers to academic success and psychoeducational preferences related to health and well-being. RESULTS: Perceived barriers to academic success reported as most problematic were sleep difficulties, stress, depression, and financial concerns. Results indicated that veterans would be interested in attending an on-campus course focusing on these areas. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: These findings contribute to the understanding of student veterans with PTS symptoms' perceived needs and inform the development of campus programs for this population. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Phase Ib/II Study of the Safety and Efficacy of Combination Therapy with Multikinase VEGF Inhibitor Pazopanib and MEK Inhibitor Trametinib In Advanced Soft Tissue Sarcoma.

Purpose: Pazopanib, a multireceptor tyrosine kinase inhibitor targeting primarily VEGFRs1-3, is approved for advanced soft tissue sarcoma (STS) and renal cell cancer. Downstream of VEGFR, trametinib is an FDA-approved MEK inhibitor used for melanoma. We hypothesized that vertical pathway inhibition using trametinib would synergize with pazopanib in advanced STS.Experimental Design: In an open-label, multicenter, investigator-initiated National Comprehensive Cancer Network (NCCN)-sponsored trial, patients with metastatic or advanced STS received pazopanib 800 mg and 2 mg of trametinib continuously for 28-day cycles. The primary endpoint was 4-month progression-free survival (PFS). Secondary endpoints were overall survival, response rate, and disease control rate.Results: Twenty-five patients were enrolled. The median age was 49 years (range, 22-77 years) and 52% were male. Median PFS was 2.27 months [95% confidence interval (CI), 1.9-3.9], and the 4-month PFS rate was 21.1% (95% CI, 9.7-45.9), which was not an improvement over the hypothesized null 4-month PFS rate of 28.3% (P = 0.79). Median overall survival was 9.0 months (95% CI, 5.7-17.7). A partial response occurred in 2 (8%) of the evaluable patients (95% CI, 1.0-26.0), one with PIK3CA E542K-mutant embryonal rhabdomyosarcoma and another with spindle cell sarcoma. The disease control rate was 14/25 (56%; 95% CI, 34.9-75.6). The most common adverse events were diarrhea (84%), nausea (64%), fatigue (56%), and hypertension (52%).Conclusions: The combination of pazopanib and trametinib was tolerable without indication of added activity of the combination in STS. Further study may be warranted in RAS/RAF aberrant sarcomas. Clin Cancer Res; 23(15); 4027-34. ©2017 AACR.