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Patients with Fontan failure are high-risk candidates for heart transplantation and other advanced therapies. Understanding the outcomes following initial heart failure consultation can help define appropriate timing of referral for advanced heart failure care.
Methods:
This is a survey study of heart failure providers seeing any Fontan patient for initial heart failure care. Part 1 of the survey captured data on clinical characteristics at the time of heart failure consultation, and Part 2, completed 30 days later, captured outcomes (death, transplant evaluation outcome, and other interventions). Patients were classified as “too late” (death or declined for transplant due to being too sick) and/or “care escalation” (ventricular assist device implanted, inotrope initiated, and/or listed for transplant), within 30 days. “Late referral” was defined as those referred too late and/or had care escalation.
Results:
Between 7/2020 and 7/2022, 77 Fontan patients (52% inpatient) had an initial heart failure consultation. Ten per cent were referred too late (6 were too sick for heart transplantation with one subsequent death, and two others died without heart transplantation evaluation, within 30 days), and 36% had care escalation (21 listed ± 5 ventricular assist device implanted ± 6 inotrope initiated). Overall, 42% were late referrals. Heart failure consultation < 1 year after Fontan surgery was strongly associated with late referral (OR 6.2, 95% CI 1.8–21.5, p=0.004).
Conclusions:
Over 40% of Fontan patients seen for an initial heart failure consultation were late referrals, with 10% dying or being declined for transplant within a month of consultation. Earlier referral, particularly for those with heart failure soon after Fontan surgery, should be encouraged.
Identifying youths most at risk to COVID-19-related mental illness is essential for the development of effective targeted interventions.
Aims
To compare trajectories of mental health throughout the pandemic in youth with and without prior mental illness and identify those most at risk of COVID-19-related mental illness.
Method
Data were collected from individuals aged 18–26 years (N = 669) from two existing cohorts: IMAGEN, a population-based cohort; and ESTRA/STRATIFY, clinical cohorts of individuals with pre-existing diagnoses of mental disorders. Repeated COVID-19 surveys and standardised mental health assessments were used to compare trajectories of mental health symptoms from before the pandemic through to the second lockdown.
Results
Mental health trajectories differed significantly between cohorts. In the population cohort, depression and eating disorder symptoms increased by 33.9% (95% CI 31.78–36.57) and 15.6% (95% CI 15.39–15.68) during the pandemic, respectively. By contrast, these remained high over time in the clinical cohort. Conversely, trajectories of alcohol misuse were similar in both cohorts, decreasing continuously (a 15.2% decrease) during the pandemic. Pre-pandemic symptom severity predicted the observed mental health trajectories in the population cohort. Surprisingly, being relatively healthy predicted increases in depression and eating disorder symptoms and in body mass index. By contrast, those initially at higher risk for depression or eating disorders reported a lasting decrease.
Conclusions
Healthier young people may be at greater risk of developing depressive or eating disorder symptoms during the COVID-19 pandemic. Targeted mental health interventions considering prior diagnostic risk may be warranted to help young people cope with the challenges of psychosocial stress and reduce the associated healthcare burden.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
The impact of a collapsing gas bubble above rigid, notched walls is considered. Such surface crevices and imperfections often function as bubble nucleation sites, and thus have a direct relation to cavitation-induced erosion and damage structures. A generic configuration is investigated numerically using a second-order accurate compressible multi-component flow solver in a two-dimensional axisymmetric coordinate system. Results show that the crevice geometry has a significant effect on the collapse dynamics, jet formation, subsequent wave dynamics and interactions. The wall-pressure distribution associated with erosion potential is a direct consequence of development and intensity of these flow phenomena.
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.
If an industrial civilization had existed on Earth many millions of years prior to our own era, what traces would it have left and would they be detectable today? We summarize the likely geological fingerprint of the Anthropocene, and demonstrate that while clear, it will not differ greatly in many respects from other known events in the geological record. We then propose tests that could plausibly distinguish an industrial cause from an otherwise naturally occurring climate event.
We analyse unsteady cavity dynamics, cavitation patterns and instability mechanisms governing partial cavitation in the flow past a sharp convergent–divergent wedge. Reproducing a recent reference experiment by numerical simulation, the investigated flow regime is characterised by large-scale cloud cavitation. In agreement with the experiments, we find that cloud shedding is dominated by the periodic occurrence of condensation shocks, propagating through the two-phase medium. The physical model is based on the homogeneous mixture approach, the assumption of thermodynamic equilibrium, and a closed-form barotropic equation of state. Compressibility of water and water vapour is taken into account. We deliberately suppress effects of molecular viscosity, in order to demonstrate that inertial effects dominate the flow evolution. We qualify the flow predictions, and validate the numerical approach by comparison with experiments. In agreement with the experiments, the vapour volume fraction within the partial cavity reaches values ${>}80\,\%$ for its spanwise average. Very good agreement is further obtained for the shedding Strouhal number, the cavity growth and collapse velocities, and for typical coherent flow structures. In accordance with the experiments, the simulations reproduce a condensation shock forming at the trailing part of the partial cavity. It is demonstrated that it satisfies locally Rankine–Hugoniot jump relations. Estimation of the shock propagation Mach number shows that the flow is supersonic. With a magnitude of only a few kPa, the pressure rise across the shock is much lower than for typical cavity collapse events. It is thus far too weak to cause cavitation erosion directly. However, by affecting the dynamics of the cavity, the flow aggressiveness can be significantly altered. Our results indicate that, in addition to classically observed re-entrant jets, condensation shocks feed an intrinsic instability mechanism of partial cavitation.
A small avalanche path near the Bridger Bowl ski area in southwestern Montana has been instrumented to measure density, velocity and dynamic friction in a flowing avalanche. These measurements, made by an array of sensors mounted in the avalanche path, have been carried out for several dry-snow avalanches. Measurements of density were made using a capacitance probe that measures the dielectric constant of any material that passes in front of it. Through a calibration procedure, the dielectric constant of a given type of snow can be related to the density of that snow. Optical sensors were used to measure light reflected from the avalanche as it passed by the sensors. Signals from adjacent optical sensors were cross-correlated to determine velocity. Density and velocity measurements were made at several heights in the avalanche, with particular attention directed near the running surface. Results indicate that avalanche deformation is concentrated near the running surface where the snow density is found to be largest. Upward from the surface, the velocity gradient falls off greatly while the density also declines.
Finally, the dynamic-friction coefficient at the base of the avalanche was found by measuring shear and normal forces on a roughened 23 cm × 28 cm aluminum plate mounted parallel and flush with the avalanche running surface. The ratio of the shear force to normal force on the plate provides a measure of the dynamic-friction coefficient at the base of the avalanche.
This paper presents the first major data release and survey description for the ANU WiFeS SuperNovA Programme. ANU WiFeS SuperNovA Programme is an ongoing supernova spectroscopy campaign utilising the Wide Field Spectrograph on the Australian National University 2.3-m telescope. The first and primary data release of this programme (AWSNAP-DR1) releases 357 spectra of 175 unique objects collected over 82 equivalent full nights of observing from 2012 July to 2015 August. These spectra have been made publicly available via the WISEREP supernova spectroscopy repository.
We analyse the ANU WiFeS SuperNovA Programme sample of Type Ia supernova spectra, including measurements of narrow sodium absorption features afforded by the high spectral resolution of the Wide Field Spectrograph instrument. In some cases, we were able to use the integral-field nature of the Wide Field Spectrograph instrument to measure the rotation velocity of the SN host galaxy near the SN location in order to obtain precision sodium absorption velocities. We also present an extensive time series of SN 2012dn, including a near-nebular spectrum which both confirms its ‘super-Chandrasekhar’ status and enables measurement of the sub-solar host metallicity at the SN site.
We report on our search for L dwarf flares using NASA's Kepler mission. Spectroscopically confirmedflares were detected with the original Kepler mission from an L1 dwarf stars. We discuss the physicalcharacteristics of these white light flares and compare them to M dwarf flares. For “habitable zone” planets, the apparent flare brightnesses would be comparable to the most powerful M dwarf flares. Weare monitoring more L dwarfs with the Kepler K2 mission. We discussthe prospect for more detections during the remainder of the K2 mission.
To examine the use of vitamin D supplements during infancy among the participants in an international infant feeding trial.
Design
Longitudinal study.
Setting
Information about vitamin D supplementation was collected through a validated FFQ at the age of 2 weeks and monthly between the ages of 1 month and 6 months.
Subjects
Infants (n 2159) with a biological family member affected by type 1 diabetes and with increased human leucocyte antigen-conferred susceptibility to type 1 diabetes from twelve European countries, the USA, Canada and Australia.
Results
Daily use of vitamin D supplements was common during the first 6 months of life in Northern and Central Europe (>80 % of the infants), with somewhat lower rates observed in Southern Europe (>60 %). In Canada, vitamin D supplementation was more common among exclusively breast-fed than other infants (e.g. 71 % v. 44 % at 6 months of age). Less than 2 % of infants in the USA and Australia received any vitamin D supplementation. Higher gestational age, older maternal age and longer maternal education were study-wide associated with greater use of vitamin D supplements.
Conclusions
Most of the infants received vitamin D supplements during the first 6 months of life in the European countries, whereas in Canada only half and in the USA and Australia very few were given supplementation.
In the run-up to Indonesia' 2009 legislative and presidential elections, very few international observers believed that the polls would pose a serious challenge to the country' continuing process of democratisation. Successful national elections had been held in 1999 and 2004, and Indonesia had conducted around 500 direct local ballots without significant problems since 2005. The expectation, therefore, was that the third postauthoritarian elections would be a routine affair.
But while the 2009 ballots did have a successful political outcome, they were in fact surprising chaotic. The conduct of the elections fell short of important basic standards of democratic electoral performance and they were organised in an ad hoc manner. The accessibility and quality of the electoral process varied widely across the country. A delayed and poorly crafted legal framework, a lack of resources and a dysfunctional voter registry all contributed to the difficulties experienced in 2009, demonstrating that Indonesia' election management processes had performed far less well than what could reasonably have been expected based on past performance. If it had not been for the convincing margin of victory achieved by President Susilo Bambang Yudhoyono and his Democratic Party (Partai Demokrat, PD) in both the legislative and presidential elections, the poor management of the elections could easily have become a catalyst for more serious political disagreements. As it was, the Constitutional Court played an extraordinary role in averting a last-minute boycott of the presidential election by the opposition candidates. Its transparent adjudication of results-related disputes after both the April and July elections was the main reason that a potentially damaging period of political paralysis was averted.
This chapter discusses the quality of management of the 2009 polls in four steps. The first section provides some background on the importance of elections for democratic consolidation, discusses Indonesia' electoral experience since 1998 and describes the main problems besetting the 2009 ballots. The second section looks at one of the chief reasons for the decline in the quality of election administration in 2009: the weakened capacity of the General Elections Commission (Komisi Pemilihan Umum, KPU) following considerable changes to Indonesia' electoral laws. The third part begins by assessing the areas of electoral organisation in which Indonesia performed satisfactorily in 2009: political parties were able to exercise freedom of expression; media reporting was balanced; the elections were conducted peacefully; and procedures for post-election dispute resolution were effective.
Earlier studies on the problems of the Adriatic Sea and the knowledge of its hydromedusae are restricted to the northern part. Will (1844) mentioned six species of hydromedusae found in the Bay of Trieste. Several studies ensued from the northern part of this sea, until Neppi (1912, 1915, 1922), Pell (1911, 1938), Kramp (1924), Babnik (1948) and Benović (1971 a) included other areas. Some specimens from the middle and southern Adriatic are mentioned in the planktonic works of Gamulin (1948, 1976), Hure (1955, 1961), Buljan, Hure & Pucher-Petković (1973) and Vučetić (1957, 1961, 1966).
A male child with multiple congenital anomalies and developmental delay is described. Cytogenetic evaluation showed that the patient was partially monosomic for the short arm of chromosome 18 and partially trisomic for the short arm of chromosome 16: a combination of chromosomal syndromes not previously described.
One of the basic and most difficult problems of our century seems to be that of the so-called ‘ developing’ nations. Although the generally accepted distinction between growth and development is sometimes questioned, one thing is certain, that in most Asian, African, and South American countries there is a need for development. International organisations and the more ‘advanced’ countries are aware of this, and make continuous efforts towards speeding up the process of development.
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