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Direct-to-consumer (DTC) genetic testing has raised questions about the accuracy of the test results, which may raise potential novel liability issues. This chapter examines potential liability exposures relating to DTC genetic testing in two main contexts. The first is potential liability for the DTC provider itself for erroneous results. Key issues in such cases will be the validity and effect of the representations and disclosures that the DTC company provides, which often informs the consumer that the results should not be relied on for medical care, disclaim any liability for any harms that may result from such reliance, and require any disputes to be resolved by mandatary arbitration. The second potential type of case is against health care providers who are presented with DTC results by their patients. Providers will often be put in a “damned if they do, damned if they don’t” predicament by such results, as both ignoring or relying on the DTC test results could create potential liabilities in certain situations. While providers can usually protect themselves by requiring validation of the DTC results by an independent laboratory, time and economic constraints may make this infeasible in some cases.
Quantitative plant biology is an interdisciplinary field that builds on a long history of biomathematics and biophysics. Today, thanks to high spatiotemporal resolution tools and computational modelling, it sets a new standard in plant science. Acquired data, whether molecular, geometric or mechanical, are quantified, statistically assessed and integrated at multiple scales and across fields. They feed testable predictions that, in turn, guide further experimental tests. Quantitative features such as variability, noise, robustness, delays or feedback loops are included to account for the inner dynamics of plants and their interactions with the environment. Here, we present the main features of this ongoing revolution, through new questions around signalling networks, tissue topology, shape plasticity, biomechanics, bioenergetics, ecology and engineering. In the end, quantitative plant biology allows us to question and better understand our interactions with plants. In turn, this field opens the door to transdisciplinary projects with the society, notably through citizen science.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
The Single Ventricle Reconstruction Trial randomised neonates with hypoplastic left heart syndrome to a shunt strategy but otherwise retained standard of care. We aimed to describe centre-level practice variation at Fontan completion.
Centre-level data are reported as median or median frequency across all centres and range of medians or frequencies across centres. Classification and regression tree analysis assessed the association of centre-level factors with length of stay and percentage of patients with prolonged pleural effusion (>7 days).
The median Fontan age (14 centres, 320 patients) was 3.1 years (range from 1.7 to 3.9), and the weight-for-age z-score was −0.56 (−1.35 + 0.44). Extra-cardiac Fontans were performed in 79% (4–100%) of patients at the 13 centres performing this procedure; lateral tunnels were performed in 32% (3–100%) at the 11 centres performing it. Deep hypothermic circulatory arrest (nine centres) ranged from 6 to 100%. Major complications occurred in 17% (7–33%). The length of stay was 9.5 days (9–12); 15% (6–33%) had prolonged pleural effusion. Centres with fewer patients (<6%) with prolonged pleural effusion and fewer (<41%) complications had a shorter length of stay (<10 days; sensitivity 1.0; specificity 0.71; area under the curve 0.96). Avoiding deep hypothermic circulatory arrest and higher weight-for-age z-score were associated with a lower percentage of patients with prolonged effusions (<9.5%; sensitivity 1.0; specificity = 0.86; area under the curve 0.98).
Fontan perioperative practices varied widely among study centres. Strategies to decrease the duration of pleural effusion and minimise complications may decrease the length of stay. Further research regarding deep hypothermic circulatory arrest is needed to understand its association with prolonged pleural effusion.
Objectives: This study aimed to evaluate the influence of lower limb loss (LL) on mental workload by assessing neurocognitive measures in individuals with unilateral transtibial (TT) versus those with transfemoral (TF) LL while dual-task walking under varying cognitive demand. Methods: Electroencephalography (EEG) was recorded as participants performed a task of varying cognitive demand while being seated or walking (i.e., varying physical demand). Results: The findings revealed both groups of participants (TT LL vs. TF LL) exhibited a similar EEG theta synchrony response as either the cognitive or the physical demand increased. Also, while individuals with TT LL maintained similar performance on the cognitive task during seated and walking conditions, those with TF LL exhibited performance decrements (slower response times) on the cognitive task during the walking in comparison to the seated conditions. Furthermore, those with TF LL neither exhibited regional differences in EEG low-alpha power while walking, nor EEG high-alpha desynchrony as a function of cognitive task difficulty while walking. This lack of alpha modulation coincided with no elevation of theta/alpha ratio power as a function of cognitive task difficulty in the TF LL group. Conclusions: This work suggests that both groups share some common but also different neurocognitive features during dual-task walking. Although all participants were able to recruit neural mechanisms critical for the maintenance of cognitive-motor performance under elevated cognitive or physical demands, the observed differences indicate that walking with a prosthesis, while concurrently performing a cognitive task, imposes additional cognitive demand in individuals with more proximal levels of amputation.
Externalizing disorders are known to be partly heritable, but the biological pathways linking genetic risk to the manifestation of these costly behaviors remain under investigation. This study sought to identify neural phenotypes associated with genomic vulnerability for externalizing disorders.
One-hundred fifty-five White, non-Hispanic veterans were genotyped using a genome-wide array and underwent resting-state functional magnetic resonance imaging. Genetic susceptibility was assessed using an independently developed polygenic score (PS) for externalizing, and functional neural networks were identified using graph theory based network analysis. Tasks of inhibitory control and psychiatric diagnosis (alcohol/substance use disorders) were used to measure externalizing phenotypes.
A polygenic externalizing disorder score (PS) predicted connectivity in a brain circuit (10 nodes, nine links) centered on left amygdala that included several cortical [bilateral inferior frontal gyrus (IFG) pars triangularis, left rostral anterior cingulate cortex (rACC)] and subcortical (bilateral amygdala, hippocampus, and striatum) regions. Directional analyses revealed that bilateral amygdala influenced left prefrontal cortex (IFG) in participants scoring higher on the externalizing PS, whereas the opposite direction of influence was observed for those scoring lower on the PS. Polygenic variation was also associated with higher Participation Coefficient for bilateral amygdala and left rACC, suggesting that genes related to externalizing modulated the extent to which these nodes functioned as communication hubs.
Findings suggest that externalizing polygenic risk is associated with disrupted connectivity in a neural network implicated in emotion regulation, impulse control, and reinforcement learning. Results provide evidence that this network represents a genetically associated neurobiological vulnerability for externalizing disorders.
Posttraumatic stress disorder (PTSD) and stress/trauma exposure are cross-sectionally associated with advanced DNA methylation age relative to chronological age. However, longitudinal inquiry and examination of associations between advanced DNA methylation age and a broader range of psychiatric disorders is lacking. The aim of this study was to examine if PTSD, depression, generalized anxiety, and alcohol-use disorders predicted acceleration of DNA methylation age over time (i.e. an increasing pace, or rate of advancement, of the epigenetic clock).
Genome-wide DNA methylation and a comprehensive set of psychiatric symptoms and diagnoses were assessed in 179 Iraq/Afghanistan war veterans who completed two assessments over the course of approximately 2 years. Two DNA methylation age indices (Horvath and Hannum), each a weighted index of an array of genome-wide DNA methylation probes, were quantified. The pace of the epigenetic clock was operationalized as change in DNA methylation age as a function of time between assessments.
Analyses revealed that alcohol-use disorders (p = 0.001) and PTSD avoidance and numbing symptoms (p = 0.02) at Time 1 were associated with an increasing pace of the epigenetic clock over time, per the Horvath (but not the Hannum) index of cellular aging.
This is the first study to suggest that posttraumatic psychopathology is longitudinally associated with a quickened pace of the epigenetic clock. Results raise the possibility that accelerated cellular aging is a common biological consequence of stress-related psychopathology, which carries implications for identifying mechanisms of stress-related cellular aging and developing interventions to slow its pace.
The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.
Acupuncture has become increasingly popular in veterinary medicine. Within the scientific literature there is debate regarding its efficacy. Due to the complex nature of acupuncture, a scoping review was undertaken to identify and categorize the evidence related to acupuncture in companion animals (dogs, cats, and horses). Our search identified 843 relevant citations. Narrative reviews represented the largest proportion of studies (43%). We identified 179 experimental studies and 175 case reports/case series that examined the efficacy of acupuncture. Dogs were the most common subjects in the experimental trials. The most common indication for use was musculoskeletal conditions, and the most commonly evaluated outcome categories among experimental trials were pain and cardiovascular parameters. The limited number of controlled trials and the breadth of indications for use, outcome categories, and types of acupuncture evaluated present challenges for future systematic reviews or meta-analyses. There is a need for high-quality randomized controlled trials addressing the most common clinical uses of acupuncture, and using consistent and clinically relevant outcomes, to inform conclusions regarding the efficacy of acupuncture in companion animals.
The SkyMapper Transient survey (SMT) is exploring variability in the southern sky by performing (a) a rolling search to discover and study supernovæ, and (b) a Target of Opportunity programme that uses the robotic SkyMapper Telescope at Siding Spring Observatory. The supernova survey is obtaining a non-targeted sample of Type Ia supernovæ (SNe Ia) at low redshifts, z < 0.1, and studying other interesting transients found with the search strategy. We have a Target of Opportunity programme with an automatic response mechanism to search for optical counterparts to gravitational-wave and fast radio-burst events; it benefits from SkyMapper’s large field of view of 5.7 sq. deg. and a rapid data reduction pipeline.
We present first results of the SMT survey. The SMT pipeline can process and obtain potential candidates within 12 hours of observation. It disentangles real transients from processing artefacts using a machine-learning algorithm. To date, SMT has discovered over 60 spectroscopically confirmed supernovæ, several peculiar objects, and over 40 SNe Ia including one (SNIa 2016hhd) which was found within the first few days of explosion. We have also participated in searches for optical counterparts of gravitational waves, fast radio bursts and other transients, and have published observations of the optical counterpart of the gravitational-wave event GW170817. We also participate in coordinated observations with the Deeper Wider Faster programme, and the Kepler K2 cosmology project.
Depression and obesity are highly prevalent, and major impacts on public health frequently co-occur. Recently, we reported that having depression moderates the effect of the FTO gene, suggesting its implication in the association between depression and obesity.
To confirm these findings by investigating the FTO polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis.
The sample consists of 6902 individuals with depression and 6799 controls from three replication cohorts and two original discovery cohorts. Linear regression models were performed to test for association between rs9939609 and body mass index (BMI), and for the interaction between rs9939609 and depression status for an effect on BMI. Fixed and random effects meta-analyses were performed using METASOFT.
In the replication cohorts, we observed a significant interaction between FTO, BMI and depression with fixed effects meta-analysis (β=0.12, P = 2.7 × 10−4) and with the Han/Eskin random effects method (P = 1.4 × 10−7) but not with traditional random effects (β = 0.1, P = 0.35). When combined with the discovery cohorts, random effects meta-analysis also supports the interaction (β = 0.12, P = 0.027) being highly significant based on the Han/Eskin model (P = 6.9 × 10−8). On average, carriers of the risk allele who have depression have a 2.2% higher BMI for each risk allele, over and above the main effect of FTO.
This meta-analysis provides additional support for a significant interaction between FTO, depression and BMI, indicating that depression increases the effect of FTO on BMI. The findings provide a useful starting point in understanding the biological mechanism involved in the association between obesity and depression.
Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity.
This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores).
Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (βstd = −0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged.
Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.
Recent trends favoring organic and sustainable turfgrass management practices have led to an increased desire for biologically based alternatives to traditional synthetic herbicides. Thaxtomin A, produced by the bacterium Streptomyces scabies, has been reported to have PRE efficacy on broadleaf weeds, but efficacy of thaxtomin A on annual grassy weeds and safety to newly seeded cool-season turfgrasses have not been reported. Field experiments were conducted to evaluate PRE efficacy of thaxtomin A on smooth crabgrass and annual bluegrass. Monthly applications of thaxtomin A from April to July controlled smooth crabgrass through July but did not provide season-long control equivalent to an industry standard PRE herbicide. An initial application of thaxtomin A at 380 g ai ha−1 followed by two applications at 190 or 380 g ha−1 at 4-wk intervals provided season-long annual bluegrass control similar to an industry standard PRE herbicide. At 380 g ha−1, thaxtomin A reduced tall fescue and perennial ryegrass cover when applied 1 wk before seeding, at seeding, or 1 wk after seeding but was safe at other application timings. Up to three applications of thaxtomin A at 380 g ha−1 at 4-wk intervals did not reduce perennial ryegrass cover. Applications to creeping bentgrass resulted in unacceptable turfgrass injury. These results suggest that thaxtomin A can suppress annual grassy weeds in tall fescue or perennial ryegrass turf when applied at least 2 wk before or after seeding. Furthermore, repeated applications of thaxtomin A can provide effective PRE control of annual bluegrass during overseeded perennial ryegrass establishment.
The Spaniards established several congregaciones or missions in central Petén, Guatemala, shortly after the 1697 conquest of the region to help control local indigenous populations. Recent investigations at the church and community of Mission San Bernabé revealed details about the entangled relations of Mayas and Spaniards. Foucault's four technologies of domination help explicate these power relations as they were played out in the small settlement and the church at its center. Material culture differed in many ways from that of the pre-conquest Itzas, but was clearly predominantly “Maya.” Spanish-style goods and burial patterns were found as were hybrid ceramic wares, the Spanish-style artifacts most common in an elite residence, reflecting that Maya elite acted as brokers with the Spaniards. The occupants also incorporated Spanish domesticates into their diets. Some changes likely resulted from various ethnic groups residing in the same settlement, but others were the product of indigenous adaptations to the situation of contact. Nevertheless, it is clear that the mission anchored a number of strategies of domination that subdued the occupants of San Bernabé.
The Amsterdam glacial basin was a major sedimentary sink from late Saalian until late Eemian (Picea zone, E6) times. The basin’s exemplary record makes it a potential reference area for the last interglacial stage. The cored Amsterdam-Terminal borehole was drilled in 1997 to provide a record throughout the Eemian interglacial. Integrated facies analysis has resulted in a detailed reconstruction of the sedimentary history.
After the Saalian ice mass had disappeared from the area, a large, deep lake had come into being, fed by the Rhine river. At the end of the glacial, the lake became smaller because it was cut off from the river-water supply, and eventually only a number of shallow pools remained in the Amsterdam basin. During the early Eemian (Betula zone, El), a seepage lake existed at the site. The lake deepened under the influence of a steadily rising sea level and finally evolved into a silled lagoon (late Quercus zone, E3). Initially, the lagoon water had fairly stable stratification, but as the sea level continued to rise the sill lost its significance, the lagoon becoming well mixed by the middle of the Corylus/Taxus zone (E4b). The phase of free exchange with the open sea ended in the early Carpinus zone (E5), when barriers developed in the sill area causing the lagoon to become stratified again. During the Late Eemian (late E5), a more dynamic system developed. The sandy barriers that had obstructed exchange with the open sea were no longer effective, and a tidally-influenced coastal lagoon formed.
The Eemian sedimentary history shown in the Amsterdam-Terminal borehole is intimately connected with the sea-level history. Because the site includes both a high-resolution pollen signal and a record of sea-level change, it has potential for correlation on various scales. Palaeomagnetic results show that the sediments predate the Blake Event, which confirms that this reversal excursion is relatively young. The U/Th age of the uppermost part of the Eemian sequence is 118.2±6.3 ka.
Objectives: To refine mild cognitive impairment (MCI) diagnostic criteria, we examined progression to dementia using two approaches to identifying MCI. Methods: A total of 1203 Framingham Heart Study participants were classified at baseline as cognitively normal or MCI (overall and four MCI subtypes) via conventional Petersen/Winblad criteria (single cognitive test impaired per domain, >1.5 SD below expectations) or Jak/Bondi criteria (two tests impaired per domain, >1 SD below norms). Cox proportional hazards models were constructed to examine the association between each MCI definition and incident dementia. Results: The Petersen/Winblad criteria classified 34% of participants as having MCI while the Jak/Bondi criteria classified 24% as MCI. Over a mean follow-up of 9.7 years, 58 participants (5%) developed incident dementia. Both MCI criteria were associated with incident dementia [Petersen/Winblad: hazards ratio (HR) = 2.64; p-value=.0002; Jak/Bondi: HR=3.30; p-value <.0001]. When both MCI definitions were included in the same model, only the Jak/Bondi definition remained statistically significantly associated with incident dementia (HR=2.47; p-value=.008). Multi-domain amnestic and single domain non-amnestic MCI subtypes were significantly associated with incident dementia for both diagnostic approaches (all p-values <.01). Conclusions: The Jak/Bondi MCI criteria had a similar association with dementia as the conventional Petersen/Winblad MCI criteria, despite classifying ~30% fewer participants as having MCI. Further exploration of alternative methods to conventional MCI diagnostic criteria is warranted. (JINS, 2016, 22, 937–943)