No Influence of Ovarian Hormones on Cerebrovascular Responses to the Valsalva Maneuver

Cerebral blood flow is modulated in part by arterial perfusion pressure and autonomic neural activity. Valsalva straining drives increases in cerebral perfusion pressure that may challenge cerebrovascular regulatory mechanisms. These challenges may be even greater during the normal menstrual cycle due to vasoactive influences of ovarian hormones. PURPOSE: To test the hypothesis that cerebral vascular responses to Valsalva straining are enhanced with increased plasma concentrations of estrogen and progesterone. METHODS: Twelve healthy eumenorrheic females (mean age 25 ± 1 yr; height 165 ± 3 cm; weight 66 ± 2 kg; mean ± SE) were studied during the early and late follicular (EF and LF) and early and late luteal (EL and LL) phases of the menstrual cycle. We recorded the ECG, beat-by-beat arterial pressure (Finometer), end-tidal CO2, and cerebral blood velocity (CBV) from the middle cerebral artery (transcranial Doppler ultrasound). Plasma ovarian hormone concentrations were assessed with high performance liquid chromatography. Supine subjects strained to an expiratory pressure of 40 mmHg for 15 seconds, and we recorded magnitudes of changes in arterial pressure and CBV. RESULTS: Compared with EF, estrogen was significantly higher during LF (111 ± 20 pg/ml) and EL (113 ± 27 pg/ml) (both P\u3c0.05). During EL (12 ± 6 pg/ml) and LL (7 ± 2 pg/ml), progesterone was significantly higher when compared with EF(1 ± .3 pg/ml) and LF(1 ± .2 pg/ml) (both P\u3c0.05). The magnitude of arterial pressure overshoot at the release of strain (an indirect indicator of peripheral sympathetic neural activation during straining) was significantly higher during LF (54 ± 9 mmHg) compared to EL and EF (both phases = 35 ± 4 mmHg; P=0.003). Changes in CBV during Valsalva straining and during release from strain were statistically identical across menstrual phases (P\u3e0.05). CONCLUSIONS: Despite indirect evidence that sympathetic neural activity during the Valsalva maneuver is increased when plasma estrogen concentrations are high, responses of the cerebral vasculature to Valsalva straining are unaffected by cycling ovarian hormones

Supporting clinician educators to achieve “work-work balance”

Clinician Educators (CE) have numerous responsibilities in different professional domains, including clinical, education, research, and administration. Many CEs face tensions trying to manage these often competing professional responsibilities and achieve “work-work balance.” Rich discussions of techniques for work-work balance amongst CEs at a medical education conference inspired the authors to gather, analyze, and summarize these techniques to share with others. In this paper we present the CE’s “Four Ps”; these are practice points that support both the aspiring and established CE to help improve their performance and productivity as CEs, and allow them to approach work-work balance

Thermographic Imaging to Detect Reductions of Central Volume Induced by Simulated Hemorrhage

Hemorrhage is the leading cause of death on the battlefield, but the magnitude of blood loss can be difficult to determine. Therefore, medics would benefit from advanced tools to detect blood loss. As skin temperature likely decreases with peripheral vasoconstriction, a portable thermographic imaging (TI) device capable of measuring skin temperature may assist in the detection hemorrhage. PURPOSE: To determine whether skin temperature measured with TI track stroke volume reductions during simulated hemorrhage. METHODS: We studied fifteen healthy volunteers (7 female and 8 male; 24±1 yrs; 171±3 cm; 69±3 kg). ECG, beat-by-beat finger arterial pressure (Finometer), respiratory rate (pneumobelt and TI at the nose), stroke volume (inert rebreathing) and continuous TI skin temperatures were measured during progressive lower body negative pressure (LBNP; -3mmHg/min) to -60 mmHg. Changes of stroke volume, respiratory rate, and skin temperature were determined with repeated measures ANOVA and linear regression. RESULTS: Respiratory rates were consistent during LBNP, and were not significantly different between the pneumobelt (13.5 ± .2) and TI (14.3 ± .3). Stroke volumes decreased directly with negative pressure applied at a rate of -1.3 ml/mmHg (R2=0.96) from a baseline value of 123 ± 8 ml to 41 ± 3 ml at -60 mmHg (P\u3c0.001). Skin temperature (assessed from the ear) did not change with LBNP (P=.17). Skin temperature was 97.06 Fo at baseline, 97.14 Fo at – 60 mmHg, and did not correlate with stroke volume (R2=0.13). CONCLUSIONS: Changes in temperature measured at the nose with TI are sensitive enough to detect inspiration and expiration, and therefore such measures have utility as a method to detect respiratory rate. Progressive LBNP of a magnitude sufficient to decrease stroke volume by 66% does not change skin temperature at the ear, and therefore TI imaging may not be a good candidate technology to pursue for hemorrhage detection

Reconfiguring Resilience for Existential Risk: Submission of Evidence to the Cabinet Office on the new UK National Resilience Strategy

This submission provides input on the UK Government's National Resilience Strategy Call for Evidence, which sought “public engagement to inform the development of a new Strategy that will outline an ambitious new vision for UK National Resilience and set objectives for achieving it.” In response, an interdisciplinary team of experts at the Centre for the Study of Existential Risk worked to prepare a concrete response to this call. In this document, we aim to share the contents of our submission for public deliberation. While we laud the UK government's inititiative to develop a new National Resilience Strategy, we argue that more work can and should be done to categorize and identify catastrophic, and existential risks; we emphasize the importance of taking a long-term perspective on mitigating and responding to the challenges these pose; and we encourage the development of a more comprehensive strategy, as these risks are all intertwined in an interconnected and complex environment. In our responses, we focus on the six broad thematic areas of the National Resilience Strategy (Risk and Resilience, Responsibilities and Accountability, Partnerships, Community, Investment, and Resilience in an Interconnected World), and provide key recommendations for improving UK national resilience, both from a general perspective on existential and global catastrophic risks, as well as with regards to policies in key risk domains such as in biorisk, climate risk, or emerging technologies within critical national infrastructure & - defence systems. While we laud the UK government's initial to develop a new National Resilience Strategy, we argue that more work can and should be done to categorize and identify catastrophic, complex, and existential risks; we emphasize a long-term perspective on mitigating and responding to the threats these pose; and we encourage the development of a more comprehensive strategy, as these risks are all intertwined in an interconnected and complex environment. In our responses, we focus on the six broad thematic areas of the National Resilience Strategy (Risk and Resilience, Responsibilities and Accountability, Partnerships, Community, Investment, and Resilience in an Interconnected World), and provide key recommendations for improving UK national resilience, both from a general perspective on existential and global catastrophic risks, as well as with regards to policies in key risk domains such as in biorisk, climate risk, or emerging technologies within critical national infrastructure & - defence systems

Changes in food neophobia and dietary habits of international students

Background International study is becoming more prevalent, yet aspects such as food neophobia often militate against the consumption of a nutritionally balanced diet of visiting students. The purpose of this paper, therefore, was to evaluate the extent to which international postgraduate students experience food neophobia, how this might vary by nationality and other demographic characteristics, and how acculturation might manifest itself in students’ dietary behaviour. Methods International postgraduate students were invited to complete a validated questionnaire during their first week at university. The questionnaire was subsequently re-administered to the same students approximately four and eight months later. Results In total, 226 usable responses were analysed, 124, 58 and 44, respectively, for the first, second and final data collection. Perhaps surprisingly, the overall food neophobia scores increased from an initial value of 27.95 (SD ± 16.95) to 33.67 (SD ± 33.67) after 3 months although when comparing European and Asian students, only the former were significantly different (p<0.05). Both Asian and European students reported small but not significant changes in their eating habits, although after 3 months significantly (p=< 0.05) less changes were reported. No significant changes were reported in students’ perceived healthiness of their diets either by nationality or over time. Conclusions Understanding the complexities of food neophobia, other aspects of dietary change and at what point these changes might take place in the acculturation process when students arrive in the UK needs to be fully understood if a climate for positive learning is to be established

Outcomes and efficacy of thoracic surgery biopsy for tumor molecular profiling in patients with advanced lung cancer

BackgroundMolecular testing of patients with advanced non–small cell lung cancer for personalized therapy often is limited by insufficient specimen from nonsurgical biopsies. We measured the feasibility, patient safety, and clinical impact of thoracic surgical tumor biopsy in patients with stage IV non–small cell lung cancer.MethodsThis is a single institution retrospective analysis. Patients with stage IV non–small cell lung cancer undergoing elective surgical tissue biopsy for molecular analysis were evaluated from March 2011 to November 2012. Perioperative specific variables were measured.ResultsTwenty-five patients with known or suspected stage IV non–small cell lung cancer undergoing surgical biopsy were identified. All cases were discussed at a multidisciplinary thoracic oncology conference or a multidisciplinary thoracic oncology clinic. Preoperative histologies included adenocarcinoma in 20 patients (80.0%) and squamous cell carcinoma in 2 patients (8.0%). Surgical procedures consisted of video-assisted thoracic surgery wedge biopsy (16, 64%), video-assisted thoracic surgery pleural biopsy (4, 16.0%), mediastinoscopy (2, 8.0%), supraclavicular/cervical lymph node excisional biopsy (3, 12.0%), and rib/chest wall resection (2, 8.0%). There were no deaths and 5 postoperative complications (20.0%). Surgery identified potentially targetable molecular information in 19 of the total patients undergoing operation (76.0%) and changed the treatment strategy in 14 patients (56.0%); 10 of the total cohort (40.0%) were enrolled into therapeutic targeted clinical trials.ConclusionsThese data suggest that thoracic surgical biopsy can be safely performed in appropriately selected patients with stage IV non–small cell lung cancer and direct personalized therapy and enrollment into relevant clinical trials. Patients with advanced-stage non–small cell lung cancer should be discussed in a multidisciplinary setting to determine the need and strategy for thoracic surgical biopsy for molecular analysis

Identification of the initial molecular changes in response to circulating angiogenic cells-mediated therapy in critical limb ischemia

BackgroundCritical limb ischemia (CLI) constitutes the most aggressive form of peripheral arterial occlusive disease, characterized by the blockade of arteries supplying blood to the lower extremities, significantly diminishing oxygen and nutrient supply. CLI patients usually undergo amputation of fingers, feet, or extremities, with a high risk of mortality due to associated comorbidities.Circulating angiogenic cells (CACs), also known as early endothelial progenitor cells, constitute promising candidates for cell therapy in CLI due to their assigned vascular regenerative properties. Preclinical and clinical assays with CACs have shown promising results. A better understanding of how these cells participate in vascular regeneration would significantly help to potentiate their role in revascularization.Herein, we analyzed the initial molecular mechanisms triggered by human CACs after being administered to a murine model of CLI, in order to understand how these cells promote angiogenesis within the ischemic tissues.MethodsBalb-c nude mice (n:24) were distributed in four different groups: healthy controls (C, n:4), shams (SH, n:4), and ischemic mice (after femoral ligation) that received either 50 mu l physiological serum (SC, n:8) or 5x10(5) human CACs (SE, n:8). Ischemic mice were sacrificed on days 2 and 4 (n:4/group/day), and immunohistochemistry assays and qPCR amplification of Alu-human-specific sequences were carried out for cell detection and vascular density measurements. Additionally, a label-free MS-based quantitative approach was performed to identify protein changes related.ResultsAdministration of CACs induced in the ischemic tissues an increase in the number of blood vessels as well as the diameter size compared to ischemic, non-treated mice, although the number of CACs decreased within time. The initial protein changes taking place in response to ischemia and more importantly, right after administration of CACs to CLI mice, are shown.ConclusionsOur results indicate that CACs migrate to the injured area; moreover, they trigger protein changes correlated with cell migration, cell death, angiogenesis, and arteriogenesis in the host. These changes indicate that CACs promote from the beginning an increase in the number of vessels as well as the development of an appropriate vascular network.Institute of Health Carlos III, ISCIII; Junta de Andaluci

A prospective randomized trial of content expertise versus process expertise in small group teaching

Article deposited according to agreement with BMC, December 6, 2010.YesFunding provided by the Open Access Authors Fund

Advancing measurements and representations of subsurface heterogeneity and dynamic processes: towards 4D hydrogeology

Essentially all hydrogeological processes are strongly influenced by the subsurface spatial heterogeneity and the temporal variation of environmental conditions, hydraulic properties, and solute concentrations. This spatial and temporal variability generally leads to effective behaviors and emerging phenomena that cannot be predicted from conventional approaches based on homogeneous assumptions and models. However, it is not always clear when, why, how, and at what scale the 4D (3D + time) nature of the subsurface needs to be considered in hydrogeological monitoring, modeling, and applications. In this paper, we discuss the interest and potential for the monitoring and characterization of spatial and temporal variability, including 4D imaging, in a series of hydrogeological processes: (1) groundwater fluxes, (2) solute transport and reaction, (3) vadose zone dynamics, and (4) surface–subsurface water interactions. We first identify the main challenges related to the coupling of spatial and temporal fluctuations for these processes. We then highlight recent innovations that have led to significant breakthroughs in high-resolution space–time imaging and modeling the characterization, monitoring, and modeling of these spatial and temporal fluctuations. We finally propose a classification of processes and applications at different scales according to their need and potential for high-resolution space–time imaging. We thus advocate a more systematic characterization of the dynamic and 3D nature of the subsurface for a series of critical processes and emerging applications. This calls for the validation of 4D imaging techniques at highly instrumented observatories and the harmonization of open databases to share hydrogeological data sets in their 4D components

Genomic and molecular analyses identify molecular subtypes of pancreatic cancer recurrence

Pancreatic cancer (PC) remains a highly lethal malignancy, and most patients with localized disease that undergo surgical resection still succumb to recurrent disease. Pattern of recurrence after pancreatectomy is heterogenous, with some studies illustrating that site of recurrence can be associated with prognosis.1 Another study suggested that tumors that develop local and distant recurrence can be regarded as a homogenous disease with similar outcomes.2 Here we investigate novel molecular determinants of recurrence pattern after pancreatectomy for PC