Potential Difference Response Research Articles

Biomarker development from functional precision medicine datasets via explainable machine learning.

10061 Background: Genomics precision medicine, deployed via tumor panel sequencing, now assists in deploying targeted therapies to cancer patients. Numerous clinical trials have investigated the utility and benefit of genomics precision medicine in multiple cancer indications. Current large-scale studies report actionability rates from ~35% to ~60%, although clinical benefit rates have been shown to be closer to 10%. While this has positively impacted patients in need, the gap between actionability and benefit remains a clinical challenge attributed to multiple factors including the complex, multi-factorial relationship between molecular status and response to therapy. These differences go beyond simple disease states and may be reflective of multiple clinically relevant features including age, sex, and race/ethnicity. Methods: We implemented a functional precision medicine (FPM) program where patients with advanced pediatric cancers were prospectively profiled via high-throughput drug sensitivity testing (DST) of FDA-approved agents on patient-derived tumor cells as well as genomics testing. The objective was to investigate the clinical utility and benefit of FPM guidance in the treatment of pediatric cancer and elucidate the relationship between molecular status of patients’ diseases and treatment responses. We generated DST data (n = 21 patients) and genomic profiling data (n = 20 patients) on pediatric cancer patients in Miami, FL, as well as post-hoc whole exome and transcriptome sequencing data (n = 13 patients) and investigated three specific relationships. Results: We analyzed the relationship between racial/ethnic background and functional response to anti-cancer agents, determining potential differences in response to therapeutic classes. Next, we examined relationships between functional response and cancer type, identifying an unanticipated lack of clustering between disease indications in patients with advanced pediatric cancers. Finally, we applied an explainable machine learning (xML) framework to the functional genomic dataset to develop multi-omics biomarker hypotheses for the chemotherapy agent idarubicin, pinpointing a potential multi-cancer relationship between response to idarubicin and known disease mechanisms in acute myeloid leukemia (AML), the sole indication where idarubicin is approved. We further present additional proof-of-concept studies generating biomarker hypotheses via xML, demonstrating a framework for development of multi-omics biomarkers. Conclusions: We are now expanding our pan-pediatric cancer functional genomics dataset through an NIMHD-funded expansion cohort (NCT05857969, n = 65 patients) to further investigate multi-omics relationships between functional and molecular characteristics and understand the role of race/ethnicity in the complex relationship.

Airflow and dynamic circumference of abdomen and thorax for adults at varied continuous positive airway pressure ventilation settings and breath rates

Continuous positive airway pressure (CPAP) ventilation is a commonly prescribed respiratory therapy providing positive end-expiratory pressure (PEEP) to assist breathing and prevent airway collapse. Setting PEEP is highly debated and it is thus primarily titrated based on symptoms of excessive or insufficient support. However, titration periods are clinician intensive and can result in barotrauma or under-oxygenation during the process. Developing model-based methods to more efficiently personalise CPAP therapy based on patient-specific response requires clinical data of lung/CPAP interactions. To this end, a trial was conducted to establish a dataset of healthy subjects lung/CPAP interaction. Pressure, flow, and tidal volume were recorded alongside secondary measures of dynamic chest and abdominal circumference, to better validate model outcomes and assess breathing modes, muscular recruitment, and effort. N = 30 subjects (15 male; 15 female) were included. Self-reported asthmatics and smokers/vapers were included, offering a preliminary assessment of any potential differences in response to CPAP from lung stiffness changes in these scenarios. Additional demographics associated with lung function (sex, age, height, and weight) were also recorded.

Abstract A011: Effectiveness of an online decision support tool in communicating information about treatment options and related risks for ductal carcinoma in situ (DCIS)

Abstract Introduction: Treatment options for women diagnosed with DCIS require careful consideration of the potential risks and benefits. An interactive decision support tool (DST) was developed to provide information about these options, including their potential long-term risk. The DST was implemented through the website www.dcisoptions.org in collaboration with the AFT-25 Comparing an Operation to Monitoring, with or without Endocrine Therapy (COMET), for low-risk DCIS study. Methods: The DST provides personalized prediction of the potential clinical impact of six different treatment options over a 10-year period. Women were asked to select one or more option, and to complete two surveys - one prior to interacting with the DST and one following interaction. Chi-square tests were used to compare the distribution of age group and DCIS grade among women who completed both surveys and those who completed the pre-tool survey only. Mean age was compared using the t-test and median age was compared using the Wilcoxon-Mann-Whitney test. The signed-rank test was used to compare the median age. The cohort that answered both surveys was analyzed for potential differences in response (pre- versus post-tool). The McNemar test was used to compare percentage distributions and the paired t-test was used to compare mean responses for questions using the Likert scale. A signed rank test was used to compare median changes from pre- to post-tool. Statistical significance was defined as P<0.05 in a two-sided test. The primary endpoint of the study was to evaluate the effectiveness of the DST in communicating information about DCIS treatment options and related risk predictions. Results: Data were collected from January 2019 to April 2022 for women (non-COMET participants) who completed the DST. Of those 976 women, 831 (85%) completed the pre-tool survey only and 145 (15%) completed both the pre- and post-tool survey. The mean age was 54.4 (9.8 SD) years. 73% of women had low/intermediate-grade DCIS, while 19% had high-grade DCIS. Among women who submitted both surveys, average time spent completing the DST was 10 minutes. Awareness of the treatment options prior to use of the DST was high (90%), except for active surveillance (85.2%) and bilateral mastectomy (84.3%). Awareness post-tool did not change significantly except for active surveillance (85.2% to 96.5% (p=0.004)). Among women who completed both surveys, the percentage who correctly identified that the chance of dying from DCIS is ‘Very Low’ increased from 60.0% to 73.8% (p<0.0001). The median estimated risk of dying from DCIS in 10 years decreased from 9% to 3% (p<0.0001). A total of 101/132 (76.5%) women that responded to a specific question about the DST found it to be ‘Very Helpful’ or ‘Helpful’ in making a treatment decision for DCIS. A limitation of the study is the lower response rate to the post-tool survey. Conclusion: In this study, we demonstrated that utilization of a DST by women diagnosed with DCIS may enable value-congruent decision making and potentially result in improved patient outcomes. Citation Format: Thomas Lynch, Ann Partridge, E. Shelley Hwang, Alastair Thompson, Elizabeth Frank, Donna Pinto, Deborah Collyar, Desiree Basila, Terry Hyslop, Marc Ryser, Anna Weiss, Anna Rapperport, Rinaa Punglia, Elissa Ozanne. Effectiveness of an online decision support tool in communicating information about treatment options and related risks for ductal carcinoma in situ (DCIS) [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr A011.

Time Course Changes In Size And Echo Intensity Of The Bicep Brachii Following Resistance Training

Following resistance training, muscles swell due to a combination of damage and an increased demand for oxygen and substrates. Cross-Sectional Area (CSA), thickness, and echo intensity (EI) are measurements have been used to monitor muscle damage and recovery. Due to the variety in responses to resistance training, this study looks at muscle recovery over time while taking into consideration the differences between males and females. PURPOSE: The purpose of this study is to examine the time course changes in muscle size and EI of the biceps bracii following an acute bout of resistance training and determine the potential differences in response between males and females. METHODS: Twenty Males (71.00 ± 2.07 cm, 74.11 ± 9.37 kg, Age 19.85 ± 0.41) and 20 females (63.35 ± 2.99 cm, 60.62 ± 8.92 kg, Age 20.00 ± 0.72). Panoramic ultrasound images were taken on the largest circumference of the bicep bracii and used to determine CSA, Muscle thickness and EI. Day 1: Participants performed four sets to failure at 70% on a bicep curl machine with a 90 second rest between sets. Ultrasounds were done pre and post exercise. Day 2 and 3: Ultrasounds only. RESULTS: LINK Excel.Sheet.12 "D:\\Ultrasound 2020\\abstract data.xlsx" "Sheet1!R2C16:R11C20" \a \f 4 \hMales and females had similar responses over time (P = 0.17-0.96) for each variable. Post exercise values for CSA, thickness, and EI *(p < 0.001) where all large but returned to baseline values by 24 hrs. Males had large muscle size ^(p < 0.001), but not difference in EI (p = 0.769). CONCLUSION: Immediately following resistance training, muscle size and EI are significantly larger for both males and females and returns to baseline in 24 hrs. Males and females exhibit similar patterns; however, males have larger muscle size and but similar EI values.

Facing salient and non-salient time sequence orientation types expressed by adverbs in English, Mandarin and Serbian

AbstractThis article intends to provide insight into how speakers of English, Mandarin, and Serbian perceive spatio-temporal relations expressed by specific pairs of adverbials. In two studies participants were presented with simple sentences describing the metaphorical movement of events on the timeline (e.g., “The meeting was moved from the morning to the afternoon.”) and were asked to decide whether the event had been moved along the sagittal, vertical or transverse axis (forward/backward, up/down, left/right). The main aim of the first study, which was conducted with 104 native speakers of Serbian, was to explore the effects of axis-orientation and individual time units on participants’ preferences and response times. The target time units used were dates, hours, months, days of the week, and years. The results showed significant differences in response times between the transverse and sagittal axis conditions on the one hand (with shorter reaction times), and the vertical axis condition on the other. Moreover, the distribution of answers showed a high degree of inconsistency when it came to moving events to a previous point in time. The main aim of the second study was to identify potential differences in responses and response times to different orientations and time units between four experimental groups: native speakers of English with no second language, native speakers of English with knowledge of a second language, native speakers of Mandarin (with English as a second language), and native speakers of Serbian (also with English as a second language). The study was conducted with 126 participants. The design of the second study was largely parallel to that of the first, but it involved three trials and different time units (parts of the day, days of the week and months). The Mandarin speakers gave the quickest responses in the first two trials when deciding on the vertical axis. Moreover, reaction times were significantly shorter in the parts-of-the-day condition (e.g., “morning”, “afternoon”), across the three trials. In addition, Mandarin speakers showed an inverted trend in responses on the sagittal axis compared to the remaining three groups. While some of our results corroborate previous research on the topic, the study also provides novel empirical evidence on how Serbian speakers conceptualize time using spatial terms.

Sex Differences in PrEsentation, Risk Factors, Drug and Interventional Therapies, and OUtcomes of Elderly PatientS with Pulmonary Embolism: Rationale and design of the SERIOUS-PE study

BackgroundSex is an important factor associated with pulmonary embolism (PE) disease presentation and outcomes, which may be related to pathobiological, social, and treatment-based differences. We are seeking to illuminate sex differences in pulmonary embolism presentation, care, and outcomes using an international registry and a national US database of people 65 years and older, the age group in which the majority of these events occur. MethodsThe Sex Differences in PrEsentation, Risk Factors, Drug and Interventional Therapies, and OUtcomes of Elderly PatientS with Pulmonary Embolism (SERIOUS-PE) study has been designed to address knowledge gaps in this area. This study will use data from the Registro Informatizado Enfermedad TromboEmbolica (RIETE) registry and the US Medicare Fee-For-Service beneficiaries. RIETE is a large international registry of patients with venous thromboembolism with data collected on PE presentation, risk factors, co-morbidities, drug and interventional therapies, as well as 30-day and 1-year outcomes (including recurrent VTE, major bleeding, and mortality). Data from US Medicare Fee-For-Service beneficiaries will be used to understand the sex differences in PE hospitalizations, advanced therapies, and outcomes at 30-day and 1-year follow-up. Assessment of outcomes in both databases will be performed in unadjusted models, as well as those adjusted for demographics, co-morbidities, and treatments, to understand whether the potential sex differences in outcomes are related to differences in risk factors and co-morbidities, potential disparities in treatment, or a plausible biological difference in women versus men. Linear trends will be assessed over time. ResultsRIETE data from March 2001 through March 2021 include 33,462 elderly patients with PE, of whom 19,294 (57.7%) were women and 14,168 (42.3%) were men. In the Medicare Fee-For-Service database, between January 2001 and December 31, 2019, 1,030,247 patients were hospitalized with a principal discharge diagnosis of PE, of whom 599,816 (58.2%) were women and 430,431 (41.8%) were men. ConclusionsFindings from the SERIOUS-PE study will help address important knowledge gaps related to sex differences in presentation and risk factors, treatment patterns, and outcomes of older adults with PE. The results may guide changes in prognostic prediction rules based on sex-specific findings, identify sex-based disparities in care delivery that should be addressed by quality improvement, or uncover potential differences in response to available therapies that warrant testing in dedicated randomized trials.

Electrochemical Detection of Ethanol in Air Using Graphene Oxide Nanosheets Combined with Au-WO3.

Detection, monitoring, and analysis of ethanol are important in various fields such as health care, food industries, and safety control. In this study, we report that a solid electrolyte gas sensor based on a proton-conducting membrane is promising for detecting ethanol in air. We focused on graphene oxide (GO) as a new solid electrolyte because it shows a high proton conductivity at room temperature. GO nanosheets are synthesized by oxidation and exfoliation of expanded graphite via the Tour’s method. GO membranes are fabricated by stacking GO nanosheets by vacuum filtration. To detect ethanol, Au-loaded WO3 is used as the sensing electrode due to the excellent activity of gold nanoparticles for the catalysis of organic molecules. Au-WO3 is coupled with rGO (reduced graphene oxide) to facilitate the electron transport in the electrode. Ce ions are intercalated into the GO membrane to facilitate proton transport. The sensor based on the Ce doped-GO membrane combined with Au-WO3/rGO as a sensing electrode shows good electric potential difference (ΔV) responses to ethanol in the air at room temperature. The sensor signal reaches more than 600 mV in response to ethanol at 40 ppm in air, making it possible to detect ethanol at a few ppb (parts per billion) level. The ethanol sensing mechanism was discussed in terms of the mixed-potential theory and catalysis of ethanol on Au-WO3.

Humoral Immunogenicity and Reactogenicity of the Standard ChAdOx1 nCoV-19 Vaccination in Taiwan.

Background: The ChAdOx1 nCoV-19 vaccine has been widely administered against SARS-CoV-2 infection; however, data regarding its immunogenicity, reactogenicity, and potential differences in responses among Asian populations remain scarce. Methods: 270 participants without prior COVID-19 were enrolled to receive ChAdOx1 nCoV-19 vaccination with a prime–boost interval of 8–9 weeks. Their specific SARS-CoV-2 antibodies, neutralizing antibody titers (NT50), platelet counts, and D-dimer levels were analyzed before and after vaccination. Results: The seroconversion rates of anti-RBD and anti-spike IgG at day 28 after a boost vaccination (BD28) were 100% and 95.19%, respectively. Anti-RBD and anti-spike IgG levels were highly correlated (r = 0.7891), which were 172.9 ± 170.4 and 179.3 ± 76.88 BAU/mL at BD28, respectively. The geometric mean concentrations (GMCs) of NT50 for all participants increased to 132.9 IU/mL (95% CI 120.0–147.1) at BD28 and were highly correlated with anti-RBD and anti-spike IgG levels (r = 0.8248 and 0.7474, respectively). Body weight index was statistically significantly associated with anti-RBD IgG levels (p = 0.035), while female recipients had higher anti-spike IgG levels (p = 0.038). The GMCs of NT50 declined with age (p = 0.0163) and were significantly different across age groups (159.7 IU/mL for 20–29 years, 99.4 IU/mL for ≥50 years, p = 0.0026). Injection-site pain, fever, and fatigue were the major reactogenicity, which were more pronounced after prime vaccination and in younger participants (<50 years). Platelet counts decreased and D-dimer levels increased after vaccination but were not clinically relevant. No serious adverse events or deaths were observed. Conclusion: The vaccine is well-tolerated and elicited robust humoral immunity against SARS-CoV-2 after standard prime–boost vaccination in Taiwanese recipients.

Graphene Oxide based Gas Sensor for Triethylamine Detection at Room Temperature

We have developed a graphene oxide (GO) based sensor to detect triethylamine at room temperature. GO is synthesized by modified Hummer’s method and spin-coated on fluorine-doped tin oxide (FTO) substrate. Structural and morphological characterizations of GO are done by XRD and FE-SEM. Sheet-like morphology of GO is observed in FESEM images. The existence of defects is confirmed by Raman spectra with a ID/IG ratio ∼ 0.94. Gas adsorption studies are carried out using scanning Kelvin probe system with various volatile organic compounds (VOCs) like ethanol, acetone, n-hexane and triethylamine. Among them, GO shows more contact potential difference (CPD) response towards triethylamine. Then, a gas sensor device is fabricated using GO and its electrical characterization is done by I-V measurements. The device shows ohmic behavior with a resistance of ∼ 50 MΩ. Thereafter, the sensor is exposed to triethylamine from 19 to 151 ppm and the sensitivity is 1.39 x 10−4 ppm−1. Interestingly, a fast response time of 11 sec is achieved at room temperature.

The Influence of Internal Erosion in Earthen Dams on the Potential Difference Response to Applied Voltage

Internal erosion is widely perceived as contributing to the failure of earthen dams. To reduce the failure risk, timely monitoring of internal erosion is an effective method in observing their internal structure evolution. A set of earthen dam model experiments were conducted. Under an applied voltage, the response potential differences (PD) at the slope of the dam models were collected before and after the impoundment of the upstream reservoir. The discrepancy among the four dam models, the influence of soil moisture content on PD, and the impact of internal erosion on PD were studied. The results show that it is acceptable to employ different dam models to simulate the development of internal erosion, although the discrepancy among the models is inevitable. The moisture content of the soil significantly affects the PD response to applied voltage. The PD increases with an increase in soil moisture content until the soil is saturated. The change in PD is correlated with the development of internal erosion. With the progression of internal erosion, the starting position for the steep increase in PD distribution continues to move toward the dam toe. In addition, the electrode stability is noted to have an effect on measured PD, which requires further studies to be clarified. This study sets the stage for the PD-based monitoring method in observing the evolution of internal erosion in earthen dams.

Roads constrain movement across behavioural processes in a partially migratory ungulate

BackgroundHuman disturbance alters animal movement globally and infrastructure, such as roads, can act as physical barriers that impact behaviour across multiple spatial scales. In ungulates, roads can particularly hamper key ecological processes such as dispersal and migration, which ensure functional connectivity among populations, and may be particularly important for population performance in highly human-dominated landscapes. The impact of roads on some aspects of ungulate behaviour has already been studied. However, potential differences in response to roads during migration, dispersal and home range movements have never been evaluated. Addressing these issues is particularly important to assess the resistance of European landscapes to the range of wildlife movement processes, and to evaluate how animals adjust to anthropogenic constraints.MethodsWe analysed 95 GPS trajectories from 6 populations of European roe deer (Capreolus capreolus) across the Alps and central Europe. We investigated how roe deer movements were affected by landscape characteristics, including roads, and we evaluated potential differences in road avoidance among resident, migratory and dispersing animals (hereafter, movement modes). First, using Net Squared Displacement and a spatio-temporal clustering algorithm, we classified individuals as residents, migrants or dispersers. We then identified the start and end dates of the migration and dispersal trajectories, and retained only the GPS locations that fell between those dates (i.e., during transience). Finally, we used the resulting trajectories to perform an integrated step selection analysis.ResultsWe found that roe deer moved through more forested areas during the day and visited less forested areas at night. They also minimised elevation gains and losses along their movement trajectories. Road crossings were strongly avoided at all times of day, but when they occurred, they were more likely to occur during longer steps and in more forested areas. Road avoidance did not vary among movement modes and, during dispersal and migration, it remained high and consistent with that expressed during home range movements.ConclusionsRoads can represent a major constraint to movement across modes and populations, potentially limiting functional connectivity at multiple ecological scales. In particular, they can affect migrating individuals that track seasonal resources, and dispersing animals searching for novel ranges.

1849P Ethnicity and socioeconomic deprivation in early phase clinical trials in a UK tertiary referral centre

Early phase trials evaluate the safety and efficacy of new treatments. To capture potential differences in responses and toxicities, trial cohorts should represent the heterogeneity of the overall population. We aimed to examine the ethnicity and socioeconomic deprivation of patients (pts) referred to the Experimental Cancer Medicine Team (ECMT) at the Christie NHS Foundation Trust.

Normal values for cervical and ocular vestibular-evoked myogenic potentials using EMG scaling: effect of body position and electrode montage

Background The clinical utility of cervical and ocular vestibular-evoked myogenic potential (cVEMP and oVEMP) is limited by variability of testing protocols and a dearth of normative data using contemporary methods for amplitude scaling. Aims/objectives To investigate the effect of body position and electrode montage on VEMP responses and to establish normative values. Material and Methods This is a repeated measures study of 44 healthy young adult subjects (22 men and 22 women). Results The highest response rate (99%) for cVEMP was achieved in the supine position with the head elevated and turned. For oVEMP, the highest response rate (90%) was achieved using nasal alar electrode montage with the subject in a sitting position. Scaled peak-to-peak amplitude was higher in males than in females for both cVEMP and oVEMP. Conclusion Normative data for 44 young healthy adults was successfully collected for two body positions for cVEMP and two head positions and two electrode montages for oVEMP. Significance Our findings describe VEMP protocols that efficiently detect VEMP responses, and we provide normative VEMP response data for young healthy subjects. We describe a potential difference in response between males and females, which may be clinically important.

Gender differences in anxiety response to high intensity white noise in rats

Prolong exposure to high intensity white noise (HIWN), defined as a heterogeneous mixture of sound waves extending over a wide frequency range, has detrimental peripheral and central consequences including cardiovascular and emotional effects. Anxiety is a common manifestation of HIWN. Although gender-dependent differences in manifestation of anxiety and/or response to treatment of this condition has been amply documented, potential differences in response to HIWN, a common exposure in combat, construction and rave disco, has not been adequately investigated. In this study, both male and female Wistar rats were subjected to HIWN for 10 consecutive days, 1 h/day. On day 11, a day after the last exposure, the performance of the rats in open field (OF) and elevated plus maze (EPM) was evaluated. Male rats showed a higher anxiety-like response to HIWN as evidenced by: lower number of entries into the open arm of the EPM, lower number of entries into central zone of OF, excess grooming in OF and more boluses in closed arm of EPM. These results indicate that gender-related differences in anxiety in general, and in response to HIWN, in particular, has to be taken into consideration when investigating the neurobiological components and/or treatment modalities.

A BAC Transgene Expressing Human CFTR under Control of Its Regulatory Elements Rescues Cftr Knockout Mice

Small-molecule modulators of cystic fibrosis transmembrane conductance regulator (CFTR) biology show promise in the treatment of cystic fibrosis (CF). A Cftr knockout (Cftr KO) mouse expressing mutants of human CFTR would advance in vivo testing of new modulators. A bacterial artificial chromosome (BAC) carrying the complete hCFTR gene including regulatory elements within 40.1 kb of DNA 5′ and 25 kb of DNA 3′ to the gene was used to generate founder mice expressing hCFTR. Whole genome sequencing indicated a single integration site on mouse chromosome 8 (8qB2) with ~6 gene copies. hCFTR+ offspring were bred to murine Cftr KO mice, producing hCFTR+/mCftr− (H+/m−) mice, which had normal survival, growth and goblet cell function as compared to wild-type (WT) mice. Expression studies showed hCFTR protein and transcripts in tissues typically expressing mCftr. Functionally, nasal potential difference and large intestinal short-circuit (Isc) responses to cAMP stimulation were similar in magnitude to WT mice, whereas small intestinal cAMP ΔIsc responses were reduced. A BAC transgenic mouse with functional hCFTR under control of its regulatory elements has been developed to enable the generation of mouse models of hCFTR mutations by gene editing for in vivo testing of new CF therapies.

Taxonomic and Functional Responses of Benthic Macroinvertebrate Communities to Hydrological and Water Quality Variations in a Heavily Regulated River

Aquatic macroinvertebrates are frequently used to evaluate river system conditions and restoration project performance. A better understanding of macroinvertebrate community responses to multiple stressors is a primary challenge for river science. In this paper, macroinvertebrate responses to hydrological and water quality variability were studied in the regulated Oglio River (northern Italy). We hypothesized that in regulated rivers the hydrological, rather than the physico-chemical conditions, would affect macroinvertebrate communities and biomonitoring tools (taxonomic metrics and functional indices). Repeated sampling (six times a year) was performed at four sites downstream of four dams in a 30 km river stretch during 2014 and 2015. Data were analysed using a linear mixed effect framework, to take into account random variation due to site and sampling date, and with multivariate analysis to track changes in community structure. A total of 69 families and 134,693 organisms were identified. The investigated metrics were mainly affected by the coefficient of variation of discharge, minimum discharge, ammonium, and temperature. The short-term dynamics of hydrological and physico-chemical variables were generally less important than the overall random effects as drivers of macroinvertebrate-based metrics. However, the relevance of a random effect (site, time, their interaction) differed depending on the biological metrics analysed. Understanding potential differences in response to short term and short stretch conditions would benefit biomonitoring and restoration procedures in both regulated and natural rivers.

Auxological characteristics of pediatric patients with permanent or transient isolated growth hormone deficiency. Response to treatment and final height

IntroductionTreatment with recombinant human growth hormone (rhGH) has been shown to improve adult height in pediatric patients with GH deficiency (GHD). However, reassessment of patients after they reach their final height shows some of them have permanent GH deficiency (PGHD), while others had a transient deficiency (TGHD). The study objective was to assess, in a cohort of pediatric patients with GHD, potential differences in response to treatment with rhGH depending on whether deficiency is permanent or transient. Materials and methodsA retrospective study of 89 patients with GHD, who were monitored from diagnosis to adult height. Clinical, auxological, radiographic and laboratory variables were collected at diagnosis, after the first year of treatment, and when they had reached their adult height. ResultsPGHD was found in 28% of patients. Initial height was −2.46±0.86 SD and −2.24±0.68 SD in subjects with PGHD and TGHD respectively. Peak GH level at diagnosis was 4.26±2.78 and 6.20±2.01ng/ml (p<0.01) in the PGHD and TGHD groups respectively. After the first year of treatment, increase in growth velocity was greater in the PGHD group: 4.33±3.53 SD vs. 2.95±2.54 SD in the PGHD group (p=0.043). Final height was −0.81±0.87 SD in the PGHD and −0.95±0.83 SD in the TGHD group (p=0.47). ConclusionsPatients with PGHD had a better short- and long-term response to rhGH. They also showed lower GH levels in stimulation tests at diagnosis, as previously reported.

Características auxológicas en pacientes pediátricos con déficit aislado permanente o transitorio de hormona del crecimiento. Respuesta al tratamiento y talla final

IntroductionTreatment with recombinant human growth hormone (rhGH) has been shown to improve adult height in pediatric patients with GH deficiency (GHD). However, reassessment of patients after they reach their final height shows some of them have permanent GH deficiency (PGHD), while others had a transient deficiency (TGHD). The study objective was to assess, in a cohort of pediatric patients with GHD, potential differences in response to treatment with rhGH depending on whether deficiency is permanent or transient. Materials and methodsA retrospective study of 89 patients with GHD, who were monitored from diagnosis to adult height. Clinical, auxological, radiographic and laboratory variables were collected at diagnosis, after the first year of treatment, and when they had reached their adult height. ResultsPGHD was found in 28% of patients. Initial height was −2.46 ± 0.86 SD and −2.24 ± 0.68 SD in subjects with PGHD and TGHD respectively. Peak GH level at diagnosis was 4.26 ± 2.78 and 6.20 ± 2.01 ng/mL (p < 0.01) in the PGHD and TGHD groups respectively. After the first year of treatment, increase in growth velocity was greater in the PGHD group: 4.33 ± 3.53 SD vs. 2.95 ± 2.54 SD in the PGHD group (p = 0.043). Final height was −0.81 ± 0.87 SD in the PGHD and −0.95 ± 0.83 SD in the TGHD group (p = 0.47). ConclusionsPatients with PGHD had a better short- and long-term response to rhGH. They also showed lower GH levels in stimulation tests at diagnosis, as previously reported.

Variance in the response of silcrete to rapid heating complicates assumptions about past heat treatment methods

Heat treatment of silcretes in the Middle Stone Age of southern Africa has been taken to indicate complex behaviour among early modern humans. This inference is based on the apparent sensitivity of silcretes to rapid changes in temperature, requiring well-regulated heating and cooling rates, and controls over maximum heating temperatures. Alternative arguments have been made that silcrete can effectively be heat treated with limited control over heating rates such that heat treatment may have been a relatively simple process. These apparently contrasting points of view elide the fact that different silcretes may respond differently to heating, and that no single approach may be appropriate in all cases. To test this proposition, we undertook a series of controlled experiments in which silcrete from two sources on the south coast of Australia were prepared into blocks of specific sizes and heated rapidly to a range of maximum temperatures in a muffle furnace. In addition to potential differences in response between sources to heat, our experiments test two factors—stone volume and maximum heating temperature—that were advanced by past explanatory models to account for the probability of sample failure (fracture) during heating. The results of our experiments suggest that the tolerance of silcretes to high heating rates is highly variable between sources within regions, and that the effect of variation between sources is stronger than the other factors examined. Additional tests on limited samples from sources in South Africa support the general relevance of our findings. From these results, we infer that optimal approaches to heating in the past were probably sensitive to the silcretes being heated.

A randomized controlled crossover trial evaluating differential responses to antihypertensive drugs (used as mono- or dual therapy) on the basis of ethnicity: The comparIsoN oF Optimal Hypertension RegiMens; part of the Ancestry Informative Markers in HYpertension program—AIM-HY INFORM trial

BackgroundEthnicity, along with a variety of genetic and environmental factors, is thought to influence the efficacy of antihypertensive therapies. Current UK guidelines use a “black versus white” approach; in doing so, they ignore the United Kingdom's largest ethnic minority: Asians from South Asia. Study designThe primary purpose of the AIM-HY INFORM trial is to identify potential differences in response to antihypertensive drugs used as mono- or dual therapy on the basis of self-defined ethnicity. A multicenter, prospective, open-label, randomized study with 2 parallel, independent trial arms (mono- and dual therapy), AIM-HY INFORM plans to enroll a total of 1,320 patients from across the United Kingdom. Those receiving monotherapy (n = 660) will enter a 3-treatment (amlodipine 10 mg od; lisinopril 20 mg od; chlorthalidone 25 mg od), 3-period crossover, lasting 24 weeks, whereas those receiving dual therapy (n = 660) will enter a 4-treatment (amlodipine 5 mg od and lisinopril 20 mg od; amlodipine 5 mg od and chlorthalidone 25 mg od; lisinopril 20 mg od and chlorthalidone 25 mg od; amiloride 10 mg od and chlorthalidone 25 mg od), 4-period crossover, lasting 32 weeks. Equal numbers of 3 ethnic groups (white, black/black British, and Asian/Asian British) will ultimately be recruited to each of the trial arms (ie, 220 participants per ethnic group per arm). Seated, automated, unattended, office, systolic blood pressure measured 8 weeks after each treatment period begins will serve as the primary outcome measure. ConclusionAIM-HY INFORM is a prospective, open-label, randomized trial which aims to evaluate first- and second-line antihypertensive therapies for multiethnic populations.