Pre-contact Agave domesticates - living legacy plants in Arizona's landscape.

BACKGROUND AND SCOPE: Agaves played a central role as multi-use plants providing food, fibre and beverage to pre-contact and historical Mesoamerican cultures. However, their importance to Indigenous Peoples in the Southwest USA and northern Mexico, where they occur because of adaptations such as CAM photosynthesis, is less well known. Archaeological research indicates the Hohokam and other pre-contact Southwestern agrarian people increased agricultural potential in this region by engineering riverine terraces and bajadas for agave dry farming. Agricultural features such as terraces and rock piles were especially characteristic of post-1000 CE with the increase of dense, aggregated populations. We present an overview of six pre-contact agave domesticates (PCADs) the Hohokam and other cultures cultivated, and their ecological and cultural attributes. These PCADs are Agave murpheyi, A. delamateri, A. phillipsiana, A. sanpedroensis, A. verdensis and A. yavapaiensis. CONCLUSION: Pre-contact agriculturists cultivated at least six once cryptic domesticated agave species in the modern Arizona landscape associated with pre-contact agricultural features, such as rock structures. Because of the longevity and primarily asexual reproduction of these agaves, relict clones have persisted to the present day, providing an opportunity to study pre-contact nutrition, trade, migration and agricultural practices. Taxonomic data imply that pre-contact farmers selected desirable attributes, initiating domestication processes that resulted in discrete lineages. These agaves are morphologically and genetically distinct from Southwest US and northern Mexico wild agaves and Mesoamerican wild and domesticated species. Additionally, the remnant clones present a rare opportunity to examine domesticates virtually unchanged since they were last cultivated prehistorically. These discoveries underline the need to view landscapes and some plant species from a cultural, rather than 'natural', perspective and discern potential cryptic species veiled by traditional taxonomic treatments. Protecting and understanding the distribution, and ecological and cultural roles of these plants require interdisciplinary collaboration between botanists, archaeologists, federal agencies and Indigenous Peoples.

Modeling the propagation of a high-average-power train of ultrashort laser pulses.

We investigate the interpulse thermal interaction of a train of ultrashort laser pulses and develop a model to describe the isobaric heating of air by a train of pulses undergoing filamentation. We calculate the heating of air from a single laser pulse and the resulting refractive index perturbation encountered by subsequent pulses, and use this to simulate the propagation of a high-power pulse train. The simulations show deflection of laser filaments by the thermal refractive index consistent with previous experimental measurements.

Management of status epilepticus: a narrative review.

Status epilepticus causes prolonged or repetitive seizures that, if left untreated, can lead to neuronal injury, severe disability, coma and death in paediatric and adult populations. While convulsive status epilepticus can be diagnosed using clinical features alone, non-convulsive status epilepticus requires confirmation by electroencephalogram. Early seizure control remains key in preventing the complications of status epilepticus. This is especially true for convulsive status epilepticus, which has stronger evidence supporting the benefit of treatment on outcomes. When status epilepticus becomes refractory, often due to gamma-aminobutyric acid and N-methyl-D-aspartate receptor modulation, anaesthetic drugs are needed to suppress seizure activity, of which there is limited evidence regarding the selection, dose or duration of their use. Seizure monitoring with electroencephalogram is often needed when patients do not return to baseline or during anaesthetic wean; however, it is resource-intensive, costly, only available in highly specialised centres and has not been shown to improve functional outcomes. Thus, the treatment goals and aggressiveness of therapy remain under debate, especially for non-convulsive status epilepticus, where prolonged therapeutic coma can lead to severe complications. This review presents an evidence-based, clinically-oriented and comprehensive review of status epilepticus and its definitions, aetiologies, treatments, outcomes and prognosis at different stages of the patient's journey.

Dynamics of the femtosecond laser-triggered spark gap.

We present space and time resolved measurements of the air hydrodynamics induced by femtosecond laser pulse excitation of the air gap between two electrodes at high potential difference. We explore both plasma-based and plasma-free gap excitation. The former uses the plasma left in the wake of femtosecond filamentation, while the latter exploits air heating by multiple-pulse resonant excitation of quantum molecular wavepackets. We find that the cumulative electrode-driven air density depression channel plays the dominant role in the gap evolution leading to breakdown. Femtosecond laser heating serves mainly to initiate the depression channel; the presence of filament plasma only augments the early heating.

Role of family caregivers regarding sexual and reproductive health for women and girls with intellectual disability: A scoping review.

BACKGROUND: While people with intellectual disability (ID) face disparities relating to sexual and reproductive health (SRH) services, little is known about the role of family caregivers who assist women and girls with ID access SRH services. This scoping review examined the findings of studies to elucidate the role of family caregivers with regard to SRH for women and girls with ID. METHOD: We used Arksey and O'Malley's six-stage scoping framework, with Levac, Colquhoun and O'Brien's revisions, to evaluate identified sources. We searched three electronic databases, six ID journals and reference lists in full-text articles. Inclusion criteria included (1) primary and secondary source research studies in peer-reviewed journals; (2) published in English; (3) all research methodologies (i.e. qualitative, quantitative, mixed methods and systematic reviews or commentaries); (4) published between 2000 and 2016; and (5) studies from any country. RESULTS: The search yielded 2062 studies; 57 articles met inclusion criteria. Most studies employed purposive, convenience or criterion sampling. Participants included people with ID, family caregivers, paid caregivers and health-care professionals. Findings were summarised thematically: (1) menstruation and menopause; (2) vaccinations and preventive screenings; (3) supporting sexuality and healthy relationships; (4) coordinating with health-care providers and (5) contraception and sterilisation. CONCLUSIONS: Findings from this scoping review underscore the need for more and better-quality research, including how family caregivers assist women and girls with ID access perinatal and preventive SRH services and sexual abuse education. Family caregivers, women and girls with ID and health-care providers need increased access to information about SRH.

Efficacy, safety and patient-reported outcomes of ledipasvir/sofosbuvir in NS3/4A protease inhibitor-experienced individuals with hepatitis C virus genotype 1 and HIV coinfection with and without cirrhosis (ANRS HC31 SOFTRIH study).

OBJECTIVES: Studies evaluating the efficacy and safety of the fixed-dose combination ledipasvir (LDV)/sofosbuvir (SOF) in patients coinfected with HIV-1 and hepatitis C virus (HCV) have mainly included treatment-naïve patients without cirrhosis. We aimed to evaluate the efficacy and safety of this combination in treatment-experienced patients with and without cirrhosis. METHODS: We conducted a multicentre, open-label, double-arm, nonrandomized study in patients coinfected with HIV-1 and HCV genotype 1 with and without cirrhosis, who had good viral suppression on their antiretroviral regimens. All patients were pretreated with a first-generation NS3/4A protease inhibitor (PI) plus pegylated interferon/ribavirin. Patients received a fixed-dose combination of LDV/SOF for 12 weeks, or for 24 weeks if cirrhosis was present. The primary endpoint was a sustained virological response (SVR) 12 weeks after the end of therapy. Secondary endpoints included safety, pharmacokinetics and patient-reported outcomes. RESULTS: Of the 68 patients enrolled, 39.7% had cirrhosis. Sixty-five patients [95.6%; 95% confidence interval (CI): 87.6-99.1%; P < 0.0001] achieved an SVR, with similar rates of SVR in those with and without cirrhosis. Tolerance was satisfactory, with mainly grade 1 or 2 adverse events. Among patient-reported outcomes, only fatigue significantly decreased at the end of treatment compared with baseline [odds ratio (OR): 0.36; 95% CI: 0.14-0.96; P = 0.04]. Mean tenofovir area under the plasma concentration-time curve (AUC) at week 4 was high, with mean ± SD AUC variation between baseline and week 4 higher in cirrhotic than in noncirrhotic patients (3261.57 ± 1920.47 ng/mL vs. 1576.15 ± 911.97 ng/mL, respectively; P = 0.03). Mild proteinuria (54.4%), hypophosphataemia (50.0%), blood bicarbonate decrease (29.4%) and hypokalaemia (13.2%) were reported. The serum creatinine level was not modified. CONCLUSIONS: LDV/SOF provided a high SVR rate in PI-experienced subjects coinfected with HCV genotype 1 and HIV-1, including patients with cirrhosis.

Energy deposition of single femtosecond filaments in the atmosphere: erratum.

In this erratum the funding section of Opt. Lett.41, 3908 (2016)OPLEDP0146-959210.1364/OL.41.003908 has been updated.

Psychiatric and substance use disorders in HIV/hepatitis C virus (HCV)-coinfected patients: does HCV clearance matter? [Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) HEPAVIH CO13 cohort].

OBJECTIVES: The objective of this nested study was to assess the prevalence of psychiatric disorders in a sample of HIV/hepatitis C virus (HCV)-coinfected patients according to their HCV status. METHODS: The nested cross-sectional study, untitled HEPAVIH-Psy survey, was performed in a subset of HIV/HCV-coinfected patients enrolled in the French Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) CO13 HEPAVIH cohort. Psychiatric disorders were screened for using the Mini International Neuropsychiatric Interview (MINI 5.0.0). RESULTS: Among the 286 patients enrolled in the study, 68 (24%) had never received HCV treatment, 87 (30%) were treatment nonresponders, 44 (15%) were currently being treated and 87 (30%) had a sustained virological response (SVR). Of the 286 patients enrolled, 121 patients (42%) screened positive for a psychiatric disorder other than suicidality and alcohol/drug abuse/dependence, 40 (14%) screened positive for alcohol abuse/dependence, 50 (18%) screened positive for drug abuse/dependence, 50 (17.5%) were receiving an antidepressant treatment and 69 (24%) were receiving an anxiolytic. Patients with an SVR did not significantly differ from the other groups in terms of psychiatric disorders. Patients receiving HCV treatment screened positive less often for an anxiety disorder. The highest rate of drug dependence/abuse was among HCV treatment-naïve patients. CONCLUSIONS: Psychiatric disorders were frequent in HIV/HCV-coinfected patients and their rates were comparable between groups, even for patients achieving an SVR. Our results emphasize the need for continuous assessment and care of coinfected patients, even after HCV clearance. Drug addiction remains an obstacle to access to HCV treatment. Despite the recent advent and continued development of directly acting antiviral agents (DAAs), it is still crucial to offer screening and comprehensive care for psychiatric and addictive disorders.

Energy deposition of single femtosecond filaments in the atmosphere.

We present spatially resolved measurements of energy deposition into atmospheric air by femtosecond laser filaments. Single filaments formed with varying laser pulse energy and pulsewidth were examined using longitudinal interferometry, sonographic probing, and direct energy loss measurements. We measure peak and average energy absorption of ∼4 µJ/cm and ∼1 µJ/cm for input pulse powers up to ∼6 times the critical power for self-focusing.

Promotoras Can Facilitate Use of Recreational Community Resources: The Mi Corazón Mi Comunidad Cohort Study.

INTRODUCTION: Limited research has documented interventions aimed at promoting use of existing recreational community resources among underserved populations. This study (HEART [Health Education Awareness Research Team] Phase 2) reports findings of an intervention (Mi Corazón Mi Comunidad) where community health workers facilitated use of diet and exercise programming at local recreational facilities among Mexican American border residents. The aim was to evaluate overall attendance rates and to assess which factors predicted higher attendance. METHOD: The design was a cohort study. From 2009 to 2013, a total of 753 participants were recruited across 5 consecutive cohorts. The intervention consisted of organized physical activity and nutrition programming at parks and recreational facilities and a free YWCA membership. Attendance at all activities was objectively recorded. Regression analyses were used to evaluate whether demographic factors, health status, and health beliefs were associated with attendance. Results Participants included mostly females at high risk for cardiovascular disease (72.4% were overweight/obese and 64% were [pre-]hypertensive). A total of 83.6% of participants attended at least one session. On average, total attendance was 21.6 sessions (range: 19.1-25.2 sessions between the different cohorts), including 16.4 physical activity and 5.2 nutrition sessions. Females (p = .003) and older participants (p < .001) attended more sessions. Participants low in acculturation (vs. high) attended on average seven more sessions (p = .003). Greater self-efficacy (p < .001), perceived benefits (p = .038), and healthy intentions (p = .024) were associated with higher attendance. Conclusions The intervention was successful in promoting use of recreational facilities among border residents at high risk for cardiovascular disease. Findings were similar across five different cohorts.

Phase I dose-escalating trial of Escherichia coli purine nucleoside phosphorylase and fludarabine gene therapy for advanced solid tumors.

BACKGROUND: The use of Escherichia coli purine nucleoside phosphorylase (PNP) to activate fludarabine has demonstrated safety and antitumor activity during preclinical analysis and has been approved for clinical investigation. PATIENTS AND METHODS: A first-in-human phase I clinical trial (NCT 01310179; IND 14271) was initiated to evaluate safety and efficacy of an intratumoral injection of adenoviral vector expressing E. coli PNP in combination with intravenous fludarabine for the treatment of solid tumors. The study was designed with escalating doses of fludarabine in the first three cohorts (15, 45, and 75 mg/m(2)) and escalating virus in the fourth (10(11)-10(12) viral particles, VP). RESULTS: All 12 study subjects completed therapy without dose-limiting toxicity. Tumor size change from baseline to final measurement demonstrated a dose-dependent response, with 5 of 6 patients in cohorts 3 and 4 achieving significant tumor regression compared with 0 responsive subjects in cohorts 1 and 2. The overall adverse event rate was not dose-dependent. Most common adverse events included pain at the viral injection site (92%), drainage/itching/burning (50%), fatigue (50%), and fever/chills/influenza-like symptoms (42%). Analysis of serum confirmed the lack of systemic exposure to fluoroadenine. Antibody response to adenovirus was detected in two patients, suggesting that neutralizing immune response is not a barrier to efficacy. CONCLUSIONS: This first-in-human clinical trial found that localized generation of fluoroadenine within tumor tissues using E. coli PNP and fludarabine is safe and effective. The pronounced effect on tumor volume after a single treatment cycle suggests that phase II studies are warranted. CLINICALTRIALSGOV IDENTIFIER: NCT01310179.

Liver-related deaths in HIV-infected patients between 1995 and 2010 in France: the Mortavic 2010 study in collaboration with the Agence Nationale de Recherche sur le SIDA (ANRS) EN 20 Mortalité 2010 survey.

OBJECTIVES: The aim of this study was to describe the proportion of liver-related diseases (LRDs) as a cause of death in HIV-infected patients in France and to compare the results with data from our five previous surveys. METHODS: In 2010, 24 clinical wards prospectively recorded all deaths occurring in around 26 000 HIV-infected patients who were regularly followed up. Results were compared with those of previous cross-sectional surveys conducted since 1995 using the same design. RESULTS: Among 230 reported deaths, 46 (20%) were related to AIDS and 30 (13%) to chronic liver diseases. Eighty per cent of patients who died from LRDs had chronic hepatitis C, 16.7% of them being coinfected with hepatitis B virus (HBV). Among patients who died from an LRD, excessive alcohol consumption was reported in 41%. At death, 80% of patients had undetectable HIV viral load and the median CD4 cell count was 349 cells/µL. The proportion of deaths and the mortality rate attributable to LRDs significantly increased between 1995 and 2005 from 1.5% to 16.7% and from 1.2‰ to 2.0‰, respectively, whereas they tended to decrease in 2010 to 13% and 1.1‰, respectively. Among liver-related causes of death, the proportion represented by hepatocellular carcinoma (HCC) dramatically increased from 5% in 1995 to 40% in 2010 (p = 0.019). CONCLUSIONS: The proportion of LRDs among causes of death in HIV-infected patients seems recently to have reached a plateau after a rapid increase during the decade 1995-2005. LRDs remain a leading cause of death in this population, mainly as a result of hepatitis C virus (HCV) coinfection, HCC representing almost half of liver-related causes of death.

Exceptions to the rule: case studies in the prediction of pathogenicity for genetic variants in hereditary cancer genes.

Based on current consensus guidelines and standard practice, many genetic variants detected in clinical testing are classified as disease causing based on their predicted impact on the normal expression or function of the gene in the absence of additional data. However, our laboratory has identified a subset of such variants in hereditary cancer genes for which compelling contradictory evidence emerged after the initial evaluation following the first observation of the variant. Three representative examples of variants in BRCA1, BRCA2 and MSH2 that are predicted to disrupt splicing, prematurely truncate the protein, or remove the start codon were evaluated for pathogenicity by analyzing clinical data with multiple classification algorithms. Available clinical data for all three variants contradicts the expected pathogenic classification. These variants illustrate potential pitfalls associated with standard approaches to variant classification as well as the challenges associated with monitoring data, updating classifications, and reporting potentially contradictory interpretations to the clinicians responsible for translating test outcomes to appropriate clinical action. It is important to address these challenges now as the model for clinical testing moves toward the use of large multi-gene panels and whole exome/genome analysis, which will dramatically increase the number of genetic variants identified.

Optical innovations in surgery.

BACKGROUND: In the past decade, there has been a major drive towards clinical translation of optical and, in particular, fluorescence imaging in surgery. In surgical oncology, radical surgery is characterized by the absence of positive resection margins, a critical factor in improving prognosis. Fluorescence imaging provides the surgeon with reliable and real-time intraoperative feedback to identify surgical targets, including positive tumour margins. It also may enable decisions on the possibility of intraoperative adjuvant treatment, such as brachytherapy, chemotherapy or emerging targeted photodynamic therapy (photoimmunotherapy). METHODS: This article reviews the use of optical imaging for intraoperative guidance and decision-making. RESULTS: Image-guided cancer surgery has the potential to be a powerful tool in guiding future surgical care. Photoimmunotherapy is a theranostic concept (simultaneous diagnosis and treatment) on the verge of clinical translation, and is highlighted as an effective combination of image-guided surgery and intraoperative treatment of residual disease. Multispectral optoacoustic tomography, a technique complementary to optical image-guided surgery, is currently being tested in humans and is anticipated to have great potential for perioperative and postoperative application in surgery. CONCLUSION: Significant advances have been achieved in real-time optical imaging strategies for intraoperative tumour detection and margin assessment. Optical imaging holds promise in achieving the highest percentage of negative surgical margins and in early detection of micrometastastic disease over the next decade.

Quasiparticle interference, quasiparticle interactions, and the origin of the charge density wave in 2H-NbSe2.

We show that a small number of intentionally introduced defects can be used as a spectroscopic tool to amplify quasiparticle interference in 2H-NbSe2 that we measure by scanning tunneling spectroscopic imaging. We show, from the momentum and energy dependence of the quasiparticle interference, that Fermi surface nesting is inconsequential to charge density wave formation in 2H-NbSe2. We demonstrate that, by combining quasiparticle interference data with additional knowledge of the quasiparticle band structure from angle resolved photoemission measurements, one can extract the wave vector and energy dependence of the important electronic scattering processes thereby obtaining direct information both about the fermiology and the interactions. In 2H-NbSe2, we use this combination to confirm that the important near-Fermi-surface electronic physics is dominated by the coupling of the quasiparticles to soft mode phonons at a wave vector different from the charge density wave ordering wave vector.

Extrahepatic manifestations in chronic hepatitis C virus carriers.

Patients with chronic hepatitis C virus (HCV) infection frequently present with extrahepatic manifestations covering a large spectrum, involving different organ systems leading to the concept of systemic HCV infection. These manifestations include autoimmune phenomena and frank autoimmune and/or rheumatic diseases and may dominate the course of chronic HCV infection. Chronic HCV infection causes liver inflammation affecting the development of hepatic diseases. HCV is also a lymphotropic virus that triggers B cells and promotes favorable conditions for B lymphocyte proliferation, including mixed cryoglobulinemia (MC) and MC vasculitis, which is the most prominent extrahepatic manifestation of chronic HCV infection. HCV may also promote a low-grade chronic systemic inflammation that may affect the development of some extrahepatic manifestations, particularly cardiovascular and cerebral vascular diseases. Recognition of extrahepatic symptoms of HCV infection could facilitate early diagnosis and treatment. The development of direct-acting antiviral agents (DDAs) has revolutionized HCV treatment. DDAs, as well as new B-cell-depleting or B-cell-modulating monoclonal antibodies, will expand the panorama of treatment options for HCV-related extrahepatic manifestations including cryoglobulinemic vasculitis. In this context, a proactive, integrated approach to HCV therapy should maximize the benefits of HCV therapy, even when liver disease is mild.

Co-existence of clonal expanded autologous and transplacental-acquired maternal T cells in recombination activating gene-deficient severe combined immunodeficiency.

It is commonly accepted that the presence of high amounts of maternal T cells excludes Omenn syndrome (OS) in severe combined immunodeficiency (SCID). We report a SCID patient with a novel mutation in the recombination activating gene (RAG)1 gene (4-BP DEL.1406 TTGC) who presented with immunodeficiency and OS. Several assays, including representatives of specific T cell receptors (TCR), Vß families and TCR-γ rearrangements, were performed in order to understand more clearly the nature and origin of the patient's T cells. The patient had oligoclonal T cells which, based on the patient-mother human leucocyte antigen (HLA)-B50 mismatch, were either autologous or of maternal origin. These cell populations were different in their numbers of regulatory T cells (T(reg)) and the diversity of TCR repertoires. This is the first description of the co-existence of large amounts of clonal expanded autologous and transplacental-acquired maternal T cells in RAG1-deficient SCID.

A comprehensive laboratory-based program for classification of variants of uncertain significance in hereditary cancer genes.

Genetic testing has the potential to guide the prevention and treatment of disease in a variety of settings, and recent technical advances have greatly increased our ability to acquire large amounts of genetic data. The interpretation of this data remains challenging, as the clinical significance of genetic variation detected in the laboratory is not always clear. Although regulatory agencies and professional societies provide some guidance regarding the classification, reporting, and long-term follow-up of variants, few protocols for the implementation of these guidelines have been described. Because the primary aim of clinical testing is to provide results to inform medical management, a variant classification program that offers timely, accurate, confident and cost-effective interpretation of variants should be an integral component of the laboratory process. Here we describe the components of our laboratory's current variant classification program (VCP), based on 20 years of experience and over one million samples tested, using the BRCA1/2 genes as a model. Our VCP has lowered the percentage of tests in which one or more BRCA1/2 variants of uncertain significance (VUSs) are detected to 2.1% in the absence of a pathogenic mutation, demonstrating how the coordinated application of resources toward classification and reclassification significantly impacts the clinical utility of testing.

Direct imaging of the acoustic waves generated by femtosecond filaments in air.

We present time-resolved measurements of the gas acoustic dynamics following interaction of spatial single- and higher-mode 50 fs, 800 nm pulses in air at 10 Hz and 1 kHz repetition rates. Results are in excellent agreement with hydrodynamic simulations. Under no conditions for single filaments do we find on-axis enhancement of gas density; this occurs only with multifilaments. We also investigate the propagation of probe beams in the gas density profile induced by a single extended filament. We find that light trapping in the expanding annular acoustic wave can create the impression of on-axis guiding in a limited temporal window.