Elevated left ventricular end diastolic pressure is a risk factor for ventricular arrhythmias in patients with tetralogy of Fallot. The objective of this retrospective study was to identify echocardiographic measures associated with left ventricular end diastolic pressure >12 mmHg in this population. Repaired tetralogy of Fallot patients age ≥13 years, who underwent a left heart catheterisation within 7 days of having an echocardiogram were evaluated. Univariate comparison was made in echocardiographic and clinical variables between patients with left ventricular end diastolic pressure >12 versus ≤12 mmHg. Ninety-four patients (54% male) with a median age of 24.6 years were included. Thirty-four (36%) had left ventricular end diastolic pressure >12 mmHg. Patients with left ventricular end diastolic pressure >12mmHg were older (median 32.9 versus 24.0 years, p = 0.02), more likely to have a history of an aortopulmonary shunt (62% versus 38%, p = 0.03), and have a diagnosis of hypertension (24% versus 7%, p = 0.03) compared to those with left ventricular end diastolic pressure ≤12 mmHg. There were no significant differences in mitral valve E/A ratio, annular e’ velocity, or E/e’ ratio between patients with left ventricular end diastolic pressure >12 versus ≤12 mmHg. Patients with left ventricular end diastolic pressure >12mmHg had larger left atrial area (mean 17.7 versus 14.0 cm2, p = 0.03) and larger left atrium anterior–posterior diameter (mean 36.0 versus 30.6 mm, p = 0.004). In conclusion, typical echocardiographic measures of left ventricular diastolic dysfunction may not be reliable in tetralogy of Fallot patients. Prospective studies with the use of novel echocardiographic measures are needed.

Here, different tissue surfaces of tomato root were characterized employing atomic force microscopy on day 7 and day 21 of growth through Young's modulus and plasticity index. These parameters provide quantitative information regarding the mechanical behavior of the tomato root under fresh conditions in different locations of the cross-section of root [cell surface of the epidermis, parenchyma (Pa), and vascular bundles (Vb)]. The results show that the mechanical parameters depend on the indented region, tissue type, and growth time. Thereby, the stiffness increases in the cell surface of epidermal tissue with increasing growth time (from 9.19 ± 0.68 to 13.90 ± 1.68 MPa) and the cell surface of Pa tissue displays the opposite behavior (from 1.74 ± 0.49 to 0.48 ± 0.55); the stiffness of cell surfaces of Vb tissue changes from 10.60 ± 0.58 to 6.37 ± 0.53 MPa, all cases showed a statistical difference (p < 0.05). Viscoelastic behavior dominates the mechanical forces in the tomato root. The current study is a contribution to a better understanding of the cell mechanics behavior of different tomato root tissues during growth.

Shiga toxin-producing Escherichia coli (STEC) infection can cause serious illness including haemolytic uraemic syndrome. The role of socio-economic status (SES) in differential clinical presentation and exposure to potential risk factors amongst STEC cases has not previously been reported in England. We conducted an observational study using a dataset of all STEC cases identified in England, 2010–2015. Odds ratios for clinical characteristics of cases and foodborne, waterborne and environmental risk factors were estimated using logistic regression, stratified by SES, adjusting for baseline demographic factors. Incidence was higher in the highest SES group compared to the lowest (RR 1.54, 95% CI 1.19–2.00). Odds of Accident and Emergency attendance (OR 1.35, 95% CI 1.10–1.75) and hospitalisation (OR 1.71, 95% CI 1.36–2.15) because of illness were higher in the most disadvantaged compared to the least, suggesting potential lower ascertainment of milder cases or delayed care-seeking behaviour in disadvantaged groups. Advantaged individuals were significantly more likely to report salad/fruit/vegetable/herb consumption (OR 1.59, 95% CI 1.16–2.17), non-UK or UK travel (OR 1.76, 95% CI 1.40–2.27; OR 1.85, 95% CI 1.35–2.56) and environmental exposures (walking in a paddock, OR 1.82, 95% CI 1.22–2.70; soil contact, OR 1.52, 95% CI 2.13–1.09) suggesting other unmeasured risks, such as person-to-person transmission, could be more important in the most disadvantaged group.

Background: Hereditary transthyretin-mediated (hATTR) amyloidosis a hereditary, multi-systemic and life-threatening disease resulting in neuropathy and cardiomyopathy. In the APOLLO study, patisiran, an investigational RNAi therapeutic targeting hepatic TTR production resulted in significant improvement in neuropathy and QoL compared to placebo and was generally well tolerated. Methods: APOLLO, a Phase 3 study of patisiran vs. placebo (NCT01960348) prespecified a cardiac subpopulation (n=126 of 225 total) that included patients with baseline left ventricular (LV) wall thickness ≥ 13mm and no medical history of aortic valve disease or hypertension. Cardiac measures included structure and function by electrocardiography, changes in NT-proBNP and 10-MWT gait speed. Results: At 18 months, patisiran treatment resulted in a mean reduction in LV wall thickness of 1 mm (p=0.017) compared to baseline, which was associated with significant improvements relative to placebo in LV end diastolic volume (+8.31 mL, p=0.036), global longitudinal strain (-1.37%, p=0.015) and NT-proBNP (55% reduction, p=7.7 x 10-8) (Figure 1). Gait speed was also improved relative to placebo (+0.35 m/sec, p=7.4 x 10-9). Rate of death or hospitalization was lower with patisiran. mNIS+7 results in the cardiac subpopulation will also be presented. Conclusions: These data suggest patisiran has the potential to halt or reverse cardiac manifestations of hATTR amyloidosis.

Background: Hereditary transthyretin-mediated (hATTR) amyloidosis is a multi-systemic, heterogenous, life-threatening disease. Patisiran resulted in significant improvement in neuropathy and QoL at 18-months compared to placebo, and was generally well-tolerated in the Phase 3 APOLLO study. Methods: Multi-center, OLE study to evaluate the efficacy and safety of long-term patisiran dosing for ≤ 5 years in hATTR amyloidosis patients with polyneuropathy who have completed the APOLLO study (NCT02510261). Endpoints include safety, tolerability and long-term efficacy of patisiran. Measures of clinical benefit are the same endpoints used in APOLLO including changes in mNIS+7 composite neuropathy impairment score and QoL (Norfolk QoL-DN) Results: As of December 2017, 184 of 186 (99%) patients who completed APOLLO and 25 patients from the Ph 2 OLE study enrolled in the Global OLE study. Baseline data for 211(APOLLO/placebo, n=49; APOLLO/patisiran, n=137 and patisiran Ph 2 OLE, n=25) patients included: median age 61 years (26-84); 74% males; 46% V30M. Interim safety data and 12-month efficacy results will be presented. Conclusions: The global OLE study includes a diverse population of hATTR amyloidosis patients. Interim data will include the long-term safety and maintenance of effect in patients continuing on patisiran, as well as the impact of treatment with patisiran on patients previously treated with placebo.

Fast ice flow is associated with the deformation of subglacial sediment. Seismic shear velocities, Vs, increase with the rigidity of material and hence can be used to distinguish soft sediment from hard bedrock substrates. Depth profiles of Vs can be obtained from inversions of Rayleigh wave dispersion curves, from passive or active-sources, but these can be highly ambiguous and lack depth sensitivity. Our novel Bayesian transdimensional algorithm, MuLTI, circumvents these issues by adding independent depth constraints to the inversion, also allowing comprehensive uncertainty analysis. We apply MuLTI to the inversion of a Rayleigh wave dataset, acquired using active-source (Multichannel Analysis of Surface Waves) techniques, to characterise sediment distribution beneath the frontal margin of Midtdalsbreen, an outlet of Norway's Hardangerjøkulen ice cap. Ice thickness (0–20 m) is constrained using co-located GPR data. Outputs from MuLTI suggest that partly-frozen sediment (Vs 500–1000 m s−1), overlying bedrock (Vs 2000–2500 m s−1), is present in patches with a thickness of ~4 m, although this approaches the resolvable limit of our Rayleigh wave frequencies (14–100 Hz). Uncertainties immediately beneath the glacier bed are <280 m s−1, implying that MuLTI cannot only distinguish bedrock and sediment substrates but does so with an accuracy sufficient for resolving variations in sediment properties.

Childhood maltreatment is associated with increased risk for most forms of psychopathology. We examine emotion dysregulation as a transdiagnostic mechanism linking maltreatment with general psychopathology. A sample of 262 children and adolescents participated; 162 (61.8%) experienced abuse or exposure to domestic violence. We assessed four emotion regulation processes (cognitive reappraisal, attention bias to threat, expressive suppression, and rumination) and emotional reactivity. Psychopathology symptoms were assessed concurrently and at a 2-year longitudinal follow-up. A general psychopathology factor (p factor), representing co-occurrence of psychopathology symptoms across multiple internalizing and externalizing domains, was estimated using confirmatory factor analysis. Maltreatment was associated with heightened emotional reactivity and greater use of expressive suppression and rumination. The association of maltreatment with attention bias varied across development, with maltreated children exhibiting a bias toward threat and adolescents a bias away from threat. Greater emotional reactivity and engagement in rumination mediated the longitudinal association between maltreatment and increased general psychopathology over time. Emotion dysregulation following childhood maltreatment occurs at multiple stages of the emotion generation process, in some cases varies across development, and serves as a transdiagnostic mechanism linking child maltreatment with general psychopathology.

The late Holocene histories of Walker Lake and the Carson Sink were reconstructed by synthesizing existing data in both basins along with new age constraints from key sites, supplemented with paleohydrologic modeling. The repeated diversions of the Walker River to the Carson Sink and then back to Walker Lake caused Walker Lake–level fluctuations spanning ± 50 m. Low lake levels at about 1000, 750, and 300 cal yr BP are time correlative to the ages of fluvial deposits along the Walker River paleochannel, when flow was directed toward the Carson Sink. The timing and duration of large lakes in the Carson Sink were further refined using moisture-sensitive tree-ring chronologies. The largest lakes required a fourfold to fivefold increase in discharge spanning decades. Addition of Walker River flow to the Carson Sink by itself is inadequate to account for the required discharge. Instead, increases in the runoff coefficient and larger areas of the drainage basin contributing surface runoff may explain the enhanced discharge required to create these large lakes.

The proton beam from the 4 MV Van de Graaff at the University of Florida has been used in conjunction with a 5 mm thick lithium drifted silicon, Si (Li), x-ray detector to do elemental analysis of biomedical samples by proton-induced x-ray emission (PIXE). Several hundred samples, mostly autopsy organs ashed at high, temperature, have been analyzed by this method. The main object of the research is the correlation between human diseases and trace element levels. The target mass has been determined by monitoring the elastically scattered protons from the sample. This technique considerably reduces the target preparation time by eliminating careful weighings or doping of each individual sample.

The 3.8 MeV proton beam from the University of Florida Van de Graaff accelerator has been used to perform trace element analysis of approximately 1200 samples (mostly from autopsies) of human tissues by proton-induced X-ray emission analysis (PIXE). Fifteen different organs and a variety of diseases have been studied. Preliminary data are presented indicating the variations of various elements in human kidney as a function of age. Analysis of samples from infants also indicate essential and non-essential elements in human kidney. On the average twelve trace elements (with atomic number equal to or larger than nineteen) are observed in each organ. Quantitative measurements have been made on several elements including K, Ca, Mn, Fe, Cu, Zn, Pb, Br, Rb, Sr, Cd, and Ba.

Many important scientific and technical problems are best addressed using multiple, microscopy-based analytical techniques that combine the strengths of complementary methods. Here, we provide two examples from biomedical challenges: unravelling the attachment zone between dental implants and bone, and uncovering the mechanism of Alzheimer's disease. They combine synchrotron-based scanning transmission X-ray microscopy (STXM) with transmission electron microscopy ((S)TEM), electron tomography (ET), EELS tomography, and/or atom probe tomography (APT). STXM provides X-ray absorption based chemical sensitivity at mesoscale resolution (10–30 nm), which complements higher spatial resolution electron microscopy and APT.

Poor compliance of prescription medication is an ongoing public health crisis. Nearly half of patients do not take their medication as prescribed, harming their own health while also increasing public health care costs. Despite these detrimental consequences, prior research has struggled to establish cost-effective and scalable interventions to improve adherence rates. We suggest that one reason for the limited success of prior interventions is that they make the personal health costs of non-adherence insufficiently prominent, while a higher saliency of these costs may motivate patients to adhere more. In the current research, we test whether an intervention that makes the personal health costs of non-compliance more salient for patients will increase their medication adherence. To do so, we conducted a randomized controlled trial with 16,191 patients across 278 UK pharmacies over a 9-month time period and manipulated the perceived consequences of medication non-adherence. We find that patients who received a treatment highlighting the personal health costs of non-compliance were significantly more likely to adhere to their medication than three comparison groups (odds ratio = 1.84, 95% confidence interval = 1.37–2.47). Shifting patients’ focus to the personal health costs of non-compliance may thus offer a potentially cost-effective and scalable approach to improving medication adherence.

A new lake-level curve for Pyramid and Winnemucca lakes, Nevada, is presented that indicates that after the ~15,500 cal yr BP Lake Lahontan high stand (1338 m), lake level fell to an elevation below 1200 m, before rising to 1230 m at the 12,000 cal yr BP Younger Dryas high stand. Lake level then fell to 1155 m by ~10,500 cal yr BP followed by a rise to 1200 m around 8000 cal yr BP. During the mid-Holocene, levels were relatively low (~1155 m) before rising to moderate levels (1190–1195 m) during the Neopluvial period (~4800–3400 cal yr BP). Lake level again plunged to about 1155 m during the late Holocene dry period (~2800–1900 cal yr BP) before rising to about 1190 m by ~1200 cal yr BP. Levels have since fluctuated within the elevation range of about 1170–1182 m except for the last 100 yr of managed river discharge when they dropped to as low as 1153 m. Late Holocene lake-level changes correspond to volume changes between 25 and 55 km3 and surface area changes between 450 and 900 km2. These lake state changes probably encompass the hydrologic variability possible under current climate boundary conditions.

We sought to define the prevalence of echocardiographic abnormalities in long-term survivors of paediatric hematopoietic stem cell transplantation and determine the utility of screening in asymptomatic patients. We analysed echocardiograms performed on survivors who underwent hematopoietic stem cell transplantation from 1982 to 2006. A total of 389 patients were alive in 2017, with 114 having an echocardiogram obtained ⩾5 years post-infusion. A total of 95 patients had echocardiogram performed for routine surveillance. The mean time post-hematopoietic stem cell transplantation was 13 years. Of 95 patients, 77 (82.1%) had ejection fraction measured, and 10/77 (13.0%) had ejection fraction z-scores ⩽−2.0, which is abnormally low. Those patients with abnormal ejection fraction were significantly more likely to have been exposed to anthracyclines or total body irradiation. Among individuals who received neither anthracyclines nor total body irradiation, only 1/31 (3.2%) was found to have an abnormal ejection fraction of 51.4%, z-score −2.73. In the cohort of 77 patients, the negative predictive value of having a normal ejection fraction given no exposure to total body irradiation or anthracyclines was 96.7% at 95% confidence interval (83.3–99.8%). Systolic dysfunction is relatively common in long-term survivors of paediatric hematopoietic stem cell transplantation who have received anthracyclines or total body irradiation. Survivors who are asymptomatic and did not receive radiation or anthracyclines likely do not require surveillance echocardiograms, unless otherwise indicated.