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Schmidt-hammer exposure-age dating (SHD) of boulders on cryoplanation terrace treads and associated bedrock cliff faces revealed Holocene ages ranging from 0 ± 825 to 8890 ± 1185 yr. The cliffs were significantly younger than the inner treads, which tended to be younger than the outer treads. Radiocarbon dates from the regolith of 3854 to 4821 cal yr BP (2σ range) indicated maximum rates of cliff recession of ~0.1 mm/yr, which suggests the onset of terrace formation before the last glacial maximum. Age, angularity, and size of clasts, together with planation across bedrock structures and the seepage of groundwater from the cliff foot, all support a process-based conceptual model of cryoplanation terrace development in which frost weathering leads to parallel cliff recession and, hence, terrace extension. The availability of groundwater during autumn freezeback is viewed as critical for frost wedging and/or the growth of segregation ice during prolonged winter frost penetration. Permafrost promotes cryoplanation by providing an impermeable frost table beneath the active layer, focusing groundwater flow, and supplying water for sediment transport by solifluction across the tread. Snow beds are considered an effect rather than a cause of cryoplanation terraces, and cryoplanation is seen as distinct from nivation.
Anecdotal evidence suggests the use of bolus tube feeding is increasing in long term home enteral tube feed (HETF) patients. A cross-sectional survey to assess the prevalence of bolus tube feeding and to characterise these patients was undertaken. Dietitians from 10 centres across the UK collected data on all adult HETF patients on the dietetic caseload receiving bolus tube feeding, (n=604, 60% male, age 58years). Demographic data, reasons for tube and bolus feeding, tube and equipment types, feeding method and patients’ complete tube feeding regimens were recorded. Over a third of patients receiving HETF used bolus feeding (37%). Patients were long-term tube fed (4.1years tube feeding, 3.5years bolus tube feeding), living at home (71%) and sedentary (70%). The majority were head and neck cancer patients (22%) who were significantly more active (79%) and lived at home (97%), while those with cerebral palsy (12%) were typically younger (age 31years) but sedentary (94%). Most patients used bolus feeding as their sole feeding method (46%), because it was quick and easy to use, as a top up to oral diet or to mimic meal times. Importantly, oral nutritional supplements (ONS) were used for bolus feeding in 85% of patients, with 51% of these being compact-style ONS (2.4kcal/ml, 125ml). This survey shows that bolus tube feeding is common amongst UK HETF patients, is used by a wide variety of patient groups and can be adapted to meet the needs of a variety of patients, clinical conditions, nutritional requirements and lifestyles.
Toys are children's first consumer products and while playing they acquire numerous skills, learn about their environment and socialise with other children and adults. Toys are adapted and used by clinicians as therapeutic devices because they allow them to create bonds and communicate with children. Aesthetical aspects should be considered early in the design process, especially since pre-schoolers’ views are still dominated by the appearance of artefacts, also known as, the perceptual salient characteristics. The study of emotions mediates the understanding of the relationships between a product, user and the process with which consumers set up preferences over products. Decisions taken in each design stage will influence whether therapeutic devices will be enjoyed by children. An experiment was carried out to test out pre-schoolers’ preferences on individual attributes: form, dimension, material (hardness and weight) and surface (appearance and texture). This study exposed dominant characteristic preferences and the fact that some are influenced by gender and age. Employing these findings in therapeutic devices will enable clinicians to better engage the children during therapy.
OBJECTIVES/SPECIFIC AIMS: Prostate cancer is the second leading cause of cancer-related death among men in the U.S. and over half of all prostate cancer patients receive radiation therapy (RT). RT induces double-strand breaks (DSBs) in DNA which are lethal to cells if not repaired. While potentially curative, 10% of low-risk patients and 50% of high-risk patients treated with RT still experience tumor recurrence. Thus, identification of novel therapeutic targets to enhance RT will likely reduce prostate cancer mortality. The only clinical approach to enhance RT is androgen deprivation therapy, which targets androgen receptor (AR) signaling; however, its use is limited due to systemic side effects. We recently reported that PRMT5 epigenetically activates AR which led us to investigate if targeting PRMT5 sensitizes prostate cancer to RT. The goal of this project is to determine if PRMT5 is a therapeutic target for prostate cancer radiosensitization and analyze its mechanistic role in response to radiation. METHODS/STUDY POPULATION: To evaluate if targeting PRMT5 may sensitize prostate cancer cells to radiation, we performed a clonogenic assay of irradiated cells. To determine if PRMT5 is required for repair of radiation-induced DSBs, we performed foci analysis via immunocytochemistry. We then used RNA-seq, qPCR, western blot, and ChIP to evaluate a potential epigenetic role of PRMT5 in activating the expression of genes critical to DSB repair. To extend our findings, we analyzed clinical data from around 18,000 of cancer patients encompassing 43 cancer types to assess if PRMT5 expression correlates with the expression of its putative target genes. RESULTS/ANTICIPATED RESULTS: Targeting PRMT5 sensitizes prostate cancer cells to radiation independently of AR status. RNA-seq analysis revealed putative PRMT5 target genes including several involved in DSB repair and G2 arrest. Mechanistically, PRMT5 functions as a master epigenetic activator of DNA damage response (DDR) genes: PRMT5 maintains the basal expression of several DDR genes including BRCA1, BRCA2, and RAD51 and is recruited upon radiation to DDR gene promoters to activate their expression via histone methylation. Targeting PRMT5 decreases expression of these genes at the protein level and hinders repair of radiation-induced DSBs in multiple cancer and non-cancer cell types. Clinically, PRMT5 expression positively correlates with the expression of these DDR genes across all 43 cancer types analyzed. DISCUSSION/SIGNIFICANCE OF IMPACT: PRMT5 acts as a master epigenetic activator of genes involved in DDR and is critical for cells to survive radiation treatment. Importantly, PRMT5 epigenetically activates multiple genes that encode for well-characterized core repair proteins involved in HR (RAD51, RAD51AP1, RAD51D, BRCA1 and BRCA2) and NHEJ (NHEJ1, Ku80, XRCC4, and DNAPKcs), which may explain why PRMT5 is essential to repair IR-induced DSBs in several cell lines. As PRMT5 is overexpressed in many human cancers and its overexpression correlates with poor prognosis, our findings suggest that more efficient DSB repair via PRMT5 overexpression in these cancers may confer survival advantages particularly following DNA damaging treatments. Lastly, because targeting DSB repair is a clinically validated therapeutic approach for cancer treatment, our findings also suggest that PRMT5 targeting may be explored as a monotherapy or in combination therapy with radiation therapy or chemotherapy for cancer treatment.
Psychotic symptoms and psychotic disorders occur at increased rates in adults with intellectual disability, including borderline intellectual functioning, compared with the general population. Little is known about the development of such symptoms in this population.
To examine whether clinical factors predictive of psychotic disorder in a familial study of schizophrenia also apply to those with intellectual disability.
Adolescents with special educational needs (SEN) were assessed with the Structured Interview for Schizotypy (SIS) and Childhood Behavioural Checklist (CBCL). These scores were used to prospectively divide participants based on their anticipated risk for psychotic disorder. A subsample were reassessed three times over 6 years, using the Positive and Negative Syndrome Scale (PANSS).
The SEN group were more symptomatic than controls throughout (Cohen's d range for PANSS subscale scores: 0.54–1.4, all P < 0.007). Over 6 years of follow-up, those above the SIS and CBCL cut-off values at baseline were more likely than those below to display morbid positive psychotic symptoms (odds ratio, 3.5; 95% CI 1.3–9.0) and develop psychotic disorder (odds ratio, 11.4; 95% CI 2.6–50.1). Baseline SIS and CBCL cut-off values predicted psychotic disorder with sensitivity of 0.67, specificity of 0.85, positive predictive value of 0.26 and negative predictive value of 0.97.
Adolescents with SEN have increased psychotic and non-psychotic symptoms. The personality and behavioural features associated with later psychotic disorder in this group are similar to those in people with familial loading. Relatively simple screening measures may help identify those in this vulnerable group who do and do not require monitoring for psychotic symptoms.
Herbicide resistance is ‘wicked’ in nature; therefore, results of the many educational efforts to encourage diversification of weed control practices in the United States have been mixed. It is clear that we do not sufficiently understand the totality of the grassroots obstacles, concerns, challenges, and specific solutions needed for varied crop production systems. Weed management issues and solutions vary with such variables as management styles, regions, cropping systems, and available or affordable technologies. Therefore, to help the weed science community better understand the needs and ideas of those directly dealing with herbicide resistance, seven half-day regional listening sessions were held across the United States between December 2016 and April 2017 with groups of diverse stakeholders on the issues and potential solutions for herbicide resistance management. The major goals of the sessions were to gain an understanding of stakeholders and their goals and concerns related to herbicide resistance management, to become familiar with regional differences, and to identify decision maker needs to address herbicide resistance. The messages shared by listening-session participants could be summarized by six themes: we need new herbicides; there is no need for more regulation; there is a need for more education, especially for others who were not present; diversity is hard; the agricultural economy makes it difficult to make changes; and we are aware of herbicide resistance but are managing it. The authors concluded that more work is needed to bring a community-wide, interdisciplinary approach to understanding the complexity of managing weeds within the context of the whole farm operation and for communicating the need to address herbicide resistance.
Seven half-day regional listening sessions were held between December 2016 and April 2017 with groups of diverse stakeholders on the issues and potential solutions for herbicide-resistance management. The objective of the listening sessions was to connect with stakeholders and hear their challenges and recommendations for addressing herbicide resistance. The coordinating team hired Strategic Conservation Solutions, LLC, to facilitate all the sessions. They and the coordinating team used in-person meetings, teleconferences, and email to communicate and coordinate the activities leading up to each regional listening session. The agenda was the same across all sessions and included small-group discussions followed by reporting to the full group for discussion. The planning process was the same across all the sessions, although the selection of venue, time of day, and stakeholder participants differed to accommodate the differences among regions. The listening-session format required a great deal of work and flexibility on the part of the coordinating team and regional coordinators. Overall, the participant evaluations from the sessions were positive, with participants expressing appreciation that they were asked for their thoughts on the subject of herbicide resistance. This paper details the methods and processes used to conduct these regional listening sessions and provides an assessment of the strengths and limitations of those processes.
Transient storage and erosion of valley fills, or sediment buffering, is a fundamental but poorly quantified process that may significantly bias fluvial sediment budgets and marine archives used for paleoclimatic and tectonic reconstructions. Prolific sediment buffering is now recognized to occur within the mountainous upper Indus River headwaters and is quantified here for the first time using optically stimulated luminescence dating, petrography, detrital zircon U-Pb geochronology, and morphometric analysis to define the timing, provenance, and volumes of prominent valley fills. This study finds that climatically modulated sediment buffering occurs over 103–104 yr time scales and results in biases in sediment compositions and volumes. Increased sediment storage coincides with strong phases of summer monsoon and winter westerlies precipitation over the late Pleistocene (32–25 ka) and mid-Holocene (~8–6 ka), followed by incision and erosion with monsoon weakening. Glacial erosion and periglacial frost-cracking drive sediment production, and monsoonal precipitation mediates sediment evacuation, in contrast to the arid Transhimalaya and monsoonal frontal Himalaya. Plateau interior basins, although volumetrically large, lack transport capacity and are consequently isolated from the modern Indus River drainage. Marginal plateau catchments that both efficiently produce and evacuate sediment may regulate the overall compositions and volumes of exported sediment from the Himalayan rain shadow.
Optical matching of ASTER (Advanced Spaceborne Thermal Emission and Reflection Radiometer) satellite image pairs is used to determine the surface velocities of major glaciers across the central Karakoram. The ASTER images were acquired in 2006 and 2007, and cover a 60×120km region over Baltoro glacier, Pakistan, and areas to the north and west. The surface velocities were compared with differential global position system (GPS) data collected on Baltoro glacier in summer 2005. The ASTER measurements reveal fine details about ice dynamics in this region. For example, glaciers are found to be active over their termini even where they are very heavily debris-covered. The characteristics of several surge-type glaciers were measured, with terminus advances of several hundred meters per year and the displacement of trunk glaciers as surge glaciers pushed into them. This study is the first synthesis of glacier velocities across this region, and provides a baseline against which both past and future changes can be compared.