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Interpersonal psychotherapy (IPT) and antidepressant medications are both first-line interventions for adult depression, but their relative efficacy in the long term and on outcome measures other than depressive symptomatology is unknown. Individual participant data (IPD) meta-analyses can provide more precise effect estimates than conventional meta-analyses. This IPD meta-analysis compared the efficacy of IPT and antidepressants on various outcomes at post-treatment and follow-up (PROSPERO: CRD42020219891). A systematic literature search conducted May 1st, 2023 identified randomized trials comparing IPT and antidepressants in acute-phase treatment of adults with depression. Anonymized IPD were requested and analyzed using mixed-effects models. The prespecified primary outcome was post-treatment depression symptom severity. Secondary outcomes were all post-treatment and follow-up measures assessed in at least two studies. IPD were obtained from 9 of 15 studies identified (N = 1536/1948, 78.9%). No significant comparative treatment effects were found on post-treatment measures of depression (d = 0.088, p = 0.103, N = 1530) and social functioning (d = 0.026, p = 0.624, N = 1213). In smaller samples, antidepressants performed slightly better than IPT on post-treatment measures of general psychopathology (d = 0.276, p = 0.023, N = 307) and dysfunctional attitudes (d = 0.249, p = 0.029, N = 231), but not on any other secondary outcomes, nor at follow-up. This IPD meta-analysis is the first to examine the acute and longer-term efficacy of IPT v. antidepressants on a broad range of outcomes. Depression treatment trials should routinely include multiple outcome measures and follow-up assessments.
Accelerating COVID-19 Treatment Interventions and Vaccines (ACTIV) was initiated by the US government to rapidly develop and test vaccines and therapeutics against COVID-19 in 2020. The ACTIV Therapeutics-Clinical Working Group selected ACTIV trial teams and clinical networks to expeditiously develop and launch master protocols based on therapeutic targets and patient populations. The suite of clinical trials was designed to collectively inform therapeutic care for COVID-19 outpatient, inpatient, and intensive care populations globally. In this report, we highlight challenges, strategies, and solutions around clinical protocol development and regulatory approval to document our experience and propose plans for future similar healthcare emergencies.
Solid-state nuclear magnetic resonance (NMR) spectroscopy, thermal analysis, and X-ray powder diffraction data on the tubular, hydrous aluminosilicate imogolite were found to be fully consistent with a previously proposed crystal structure consisting of a rolled-up, 6-coordinate Al-O(OH) sheet, bonded to isolated orthosilicate groups. The calculated 29Si chemical shift of this structure agreed with the observed shift within 3 ppm. Thermal dehydroxylation of the Al-O(OH) sheet produced predominantly NMR-transparent 5-coordinate Al, but a few 4- and 6-coordinate sites and some residual hydroxyl groups may also have formed, as shown by NMR spectroscopy. Changes in the 29Si NMR spectrum on dehydroxylation suggest a condensation of the orthosilicate groups, but steric considerations rule out bonding between adjacent silicons. To account for these observations, an alternative mechanism to orthosilicate condensation has been proposed, involving the fracture and unrolling of the tubes, followed by the condensation of fragments to form a layer structure. The layer structure has a calculated 29Si chemical shift of -95.6 ppm, in good agreement with the observed value of -93 ppm.
There are little reported data on the perspectives of fathers caring for children with chronic conditions. Although survival of children with advanced heart disease has improved, long-term morbidity remains high. This study describes the experience and prognostic awareness of fathers of hospitalised children with advanced heart disease.
Methods:
Cross-sectional survey study of parents caring for children hospitalised with advanced heart disease admitted for ≥ 7 days over a one-year period. One parent per patient completed surveys, resulting in 27 father surveys. Data were analysed using descriptive methods.
Results:
Nearly all (96%) of the fathers reported understanding their child’s prognosis “extremely well” or “well,” and 59% felt they were “very prepared” for their child’s medical problems. However, 58% of fathers wanted to know more about prognosis, and 22% thought their child’s team knew something about prognosis that they did not. Forty-one per cent of fathers did not think that their child would have lifelong limitations, and 32% anticipated normal life expectancies. All 13 fathers who had a clinical discussion of what would happen if their child got sicker found this conversation helpful. Nearly half (43%) of the fathers receiving new prognostic information or changes to treatment course found it “somewhat” or “a little” confusing.
Conclusions:
Fathers report excellent understanding of their child’s illness and a positive experience around expressing their hopes and fears. Despite this, there remain many opportunities to improve communication, prognostic awareness, and participation in informed decision-making of fathers of children hospitalised with advanced heart disease.
Female fertility is a complex trait with age-specific changes in spontaneous dizygotic (DZ) twinning and fertility. To elucidate factors regulating female fertility and infertility, we conducted a genome-wide association study (GWAS) on mothers of spontaneous DZ twins (MoDZT) versus controls (3273 cases, 24,009 controls). This is a follow-up study to the Australia/New Zealand (ANZ) component of that previously reported (Mbarek et al., 2016), with a sample size almost twice that of the entire discovery sample meta-analysed in the previous article (and five times the ANZ contribution to that), resulting from newly available additional genotyping and representing a significant increase in power. We compare analyses with and without male controls and show unequivocally that it is better to include male controls who have been screened for recent family history, than to use only female controls. Results from the SNP based GWAS identified four genomewide significant signals, including one novel region, ZFPM1 (Zinc Finger Protein, FOG Family Member 1), on chromosome 16. Previous signals near FSHB (Follicle Stimulating Hormone beta subunit) and SMAD3 (SMAD Family Member 3) were also replicated (Mbarek et al., 2016). We also ran the GWAS with a dominance model that identified a further locus ADRB2 on chr 5. These results have been contributed to the International Twinning Genetics Consortium for inclusion in the next GWAS meta-analysis (Mbarek et al., in press).
Patients diagnosed with coronavirus disease 2019 (COVID-19) aerosolize severe acute respiratory coronavirus virus 2 (SARS-CoV-2) via respiratory efforts, expose, and possibly infect healthcare personnel (HCP). To prevent transmission of SARS-CoV-2 HCP have been required to wear personal protective equipment (PPE) during patient care. Early in the COVID-19 pandemic, face shields were used as an approach to control HCP exposure to SARS-CoV-2, including eye protection.
Methods:
An MS2 bacteriophage was used as a surrogate for SARS-CoV-2 and was aerosolized using a coughing machine. A simulated HCP wearing a disposable plastic face shield was placed 0.41 m (16 inches) away from the coughing machine. The aerosolized virus was sampled using SKC biosamplers on the inside (near the mouth of the simulated HCP) and the outside of the face shield. The aerosolized virus collected by the SKC Biosampler was analyzed using a viability assay. Optical particle counters (OPCs) were placed next to the biosamplers to measure the particle concentration.
Results:
There was a statistically significant reduction (P < .0006) in viable virus concentration on the inside of the face shield compared to the outside of the face shield. The particle concentration was significantly lower on the inside of the face shield compared to the outside of the face shield for 12 of the 16 particle sizes measured (P < .05).
Conclusions:
Reductions in virus and particle concentrations were observed on the inside of the face shield; however, viable virus was measured on the inside of the face shield, in the breathing zone of the HCP. Therefore, other exposure control methods need to be used to prevent transmission from virus aerosol.
Early in the COVID-19 pandemic, the World Health Organization stressed the importance of daily clinical assessments of infected patients, yet current approaches frequently consider cross-sectional timepoints, cumulative summary measures, or time-to-event analyses. Statistical methods are available that make use of the rich information content of longitudinal assessments. We demonstrate the use of a multistate transition model to assess the dynamic nature of COVID-19-associated critical illness using daily evaluations of COVID-19 patients from 9 academic hospitals. We describe the accessibility and utility of methods that consider the clinical trajectory of critically ill COVID-19 patients.
Microscopic examination of blood smears remains the gold standard for laboratory inspection and diagnosis of malaria. Smear inspection is, however, time-consuming and dependent on trained microscopists with results varying in accuracy. We sought to develop an automated image analysis method to improve accuracy and standardization of smear inspection that retains capacity for expert confirmation and image archiving. Here, we present a machine learning method that achieves red blood cell (RBC) detection, differentiation between infected/uninfected cells, and parasite life stage categorization from unprocessed, heterogeneous smear images. Based on a pretrained Faster Region-Based Convolutional Neural Networks (R-CNN) model for RBC detection, our model performs accurately, with an average precision of 0.99 at an intersection-over-union threshold of 0.5. Application of a residual neural network-50 model to infected cells also performs accurately, with an area under the receiver operating characteristic curve of 0.98. Finally, combining our method with a regression model successfully recapitulates intraerythrocytic developmental cycle with accurate lifecycle stage categorization. Combined with a mobile-friendly web-based interface, called PlasmoCount, our method permits rapid navigation through and review of results for quality assurance. By standardizing assessment of Giemsa smears, our method markedly improves inspection reproducibility and presents a realistic route to both routine lab and future field-based automated malaria diagnosis.
Antidepressant medication and interpersonal psychotherapy (IPT) are both recommended interventions in depression treatment guidelines based on literature reviews and meta-analyses. However, ‘conventional’ meta-analyses comparing their efficacy are limited by their reliance on reported study-level information and a narrow focus on depression outcome measures assessed at treatment completion. Individual participant data (IPD) meta-analysis, considered the gold standard in evidence synthesis, can improve the quality of the analyses when compared with conventional meta-analysis.
Aims
We describe the protocol for a systematic review and IPD meta-analysis comparing the efficacy of antidepressants and IPT for adult acute-phase depression across a range of outcome measures, including depressive symptom severity as well as functioning and well-being, at both post-treatment and follow-up (PROSPERO: CRD42020219891).
Method
We will conduct a systematic literature search in PubMed, PsycINFO, Embase and the Cochrane Library to identify randomised clinical trials comparing antidepressants and IPT in the acute-phase treatment of adults with depression. We will invite the authors of these studies to share the participant-level data of their trials. One-stage IPD meta-analyses will be conducted using mixed-effects models to assess treatment effects at post-treatment and follow-up for all outcome measures that are assessed in at least two studies.
Conclusions
This will be the first IPD meta-analysis examining antidepressants versus IPT efficacy. This study has the potential to enhance our knowledge of depression treatment by comparing the short- and long-term effects of two widely used interventions across a range of outcome measures using state-of-the-art statistical techniques.
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 radiocarbon (14C) calibration curve so far contains annually resolved data only for a short period of time. With accelerator mass spectrometry (AMS) matching the precision of decay counting, it is now possible to efficiently produce large datasets of annual resolution for calibration purposes using small amounts of wood. The radiocarbon intercomparison on single-year tree-ring samples presented here is the first to investigate specifically possible offsets between AMS laboratories at high precision. The results show that AMS laboratories are capable of measuring samples of Holocene age with an accuracy and precision that is comparable or even goes beyond what is possible with decay counting, even though they require a thousand times less wood. It also shows that not all AMS laboratories always produce results that are consistent with their stated uncertainties. The long-term benefits of studies of this kind are more accurate radiocarbon measurements with, in the future, better quantified uncertainties.
Balloon aortic valvuloplasty and open surgical valvotomy are procedures to treat neonatal aortic stenosis, and there is controversy as to which method has superior outcomes.
Methods:
We reviewed the records of patients at our institution since 2000 who had a balloon aortic valvuloplasty or surgical valvotomy via an open commissurotomy prior to 2 months of age.
Results:
Forty patients had balloon aortic valvuloplasty and 15 patients had surgical valvotomy via an open commissurotomy. There was no difference in post-procedure mean gradient by transthoracic echocardiogram, which were 25.8 mmHg for balloon aortic valvuloplasty and 26.2 mmHg for surgical valvotomy, p = 0.87. Post-procedure, 15% of balloon aortic valvuloplasty patients had moderate aortic insufficiency and 2.5% of patients had severe aortic insufficiency, while no surgical valvotomy patients had moderate or severe aortic insufficiency. The average number of post-procedure hospital days was 14.2 for balloon aortic valvuloplasty and 19.8 for surgical valvotomy (p = 0.52). Freedom from re-intervention was 69% for balloon aortic valvuloplasty and 67% for surgical valvotomy at 1 year, and 43% for balloon aortic valvuloplasty and 67% for surgical valvotomy at 5 years (p = 0.60).
Conclusions:
Balloon aortic valvuloplasty and surgical valvotomy provide similar short-term reduction in valve gradient. Balloon aortic valvuloplasty has a slightly shorter but not statistically significant hospital stay. Freedom from re-intervention is similar at 1 year. At 5 years, it is slightly higher in surgical valvotomy, though not statistically different. Balloon aortic valvuloplasty had a higher incidence of significant aortic insufficiency. Long-term comparisons cannot be made given the lack of long-term follow-up with surgical valvotomy.
The Ross procedure involves using the native pulmonary valve for aortic valve replacement then replacing the pulmonary valve with an allograft or xenograft. We aimed to compare our age-matched experience with the bovine jugular vein conduit and the pulmonary homograft for pulmonary valve replacement during the Ross procedure in children.
Methods:
Between 1998 and 2016, 15 patients <18 years of age underwent a Ross procedure using the bovine jugular vein conduit (Ross-Bovine Jugular Vein Conduit) at our institution. These patients were age-matched with 15 patients who had the Ross operation with a standard pulmonary homograft for right ventricular outflow tract reconstruction (Ross-Pulmonary Homograft). Paper and electronic medical records were retrospectively reviewed.
Results:
The median age of the Ross-Bovine Jugular Vein Conduit and Ross-Pulmonary Homograft patients were 4.8 years (interquartile range 1.1–6.6) and 3.3 years (interquartile 1.2–7.6), respectively (p = 0.6). The median follow-up time for the Ross-Bovine Jugular Vein Conduit and Ross-Pulmonary Homograft groups were 1.7 years (interquartile range 0.5–4.9) and 6.8 years (interquartile range 1.9–13.4), respectively (p = 0.03). Overall, 5-year survival, freedom from redo aortic valve replacement, and freedom from pulmonary valve replacement were similar between groups.
Conclusion:
The bovine jugular vein conduit and pulmonary homograft have favourable mid-term durability when used for right ventricular outflow tract reconstruction for the Ross operation. The bovine jugular vein conduit may be a suitable replacement for appropriately sized patients undergoing a Ross aortic valve replacement, though longer follow-up is needed.
We have observed the G23 field of the Galaxy AndMass Assembly (GAMA) survey using the Australian Square Kilometre Array Pathfinder (ASKAP) in its commissioning phase to validate the performance of the telescope and to characterise the detected galaxy populations. This observation covers ~48 deg2 with synthesised beam of 32.7 arcsec by 17.8 arcsec at 936MHz, and ~39 deg2 with synthesised beam of 15.8 arcsec by 12.0 arcsec at 1320MHz. At both frequencies, the root-mean-square (r.m.s.) noise is ~0.1 mJy/beam. We combine these radio observations with the GAMA galaxy data, which includes spectroscopy of galaxies that are i-band selected with a magnitude limit of 19.2. Wide-field Infrared Survey Explorer (WISE) infrared (IR) photometry is used to determine which galaxies host an active galactic nucleus (AGN). In properties including source counts, mass distributions, and IR versus radio luminosity relation, the ASKAP-detected radio sources behave as expected. Radio galaxies have higher stellar mass and luminosity in IR, optical, and UV than other galaxies. We apply optical and IR AGN diagnostics and find that they disagree for ~30% of the galaxies in our sample. We suggest possible causes for the disagreement. Some cases can be explained by optical extinction of the AGN, but for more than half of the cases we do not find a clear explanation. Radio sources aremore likely (~6%) to have an AGN than radio quiet galaxies (~1%), but the majority of AGN are not detected in radio at this sensitivity.
The initial classic Fontan utilising a direct right atrial appendage to pulmonary artery anastomosis led to numerous complications. Adults with such complications may benefit from conversion to a total cavo-pulmonary connection, the current standard palliation for children with univentricular hearts.
Methods:
A single institution, retrospective chart review was conducted for all Fontan conversion procedures performed from July, 1999 through January, 2017. Variables analysed included age, sex, reason for Fontan conversion, age at Fontan conversion, and early mortality or heart transplant within 1 year after Fontan conversion.
Results:
A total of 41 Fontan conversion patients were identified. Average age at Fontan conversion was 24.5 ± 9.2 years. Dominant left ventricular physiology was present in 37/41 (90.2%) patients. Right-sided heart failure occurred in 39/41 (95.1%) patients and right atrial dilation was present in 33/41 (80.5%) patients. The most common causes for Fontan conversion included atrial arrhythmia in 37/41 (90.2%), NYHA class II HF or greater in 31/41 (75.6%), ventricular dysfunction in 23/41 (56.1%), and cirrhosis or fibrosis in 7/41 (17.1%) patients. Median post-surgical follow-up was 6.2 ± 4.9 years. Survival rates at 30 days, 1 year, and greater than 1-year post-Fontan conversion were 95.1, 92.7, and 87.8%, respectively. Two patients underwent heart transplant: the first within 1 year of Fontan conversion for heart failure and the second at 5.3 years for liver failure.
Conclusions:
Fontan conversion should be considered early when atrial arrhythmias become common rather than waiting for severe heart failure to ensue, and Fontan conversion can be accomplished with an acceptable risk profile.
Complete lattice parameters have been determined at a series of temperatures up to 950 °C using a furnace on a powder diffractometer for six synthetic supposed equilibrium albites, a nonequilibrium albite, two natural albites, and a heat-treated natural albite. The supposed equilibrium albites were prepared hydrothermally by MacKenzie (1957) for long periods of time and reached or nearly reached a state of no further change at their temperatures of synthesis between 500 and 1000 °C. A crystal of natural albite and three crystals of heat-treated natural albite were studied by high-temperature, single-crystal methods on a Buerger precession camera up to 1000 °C for comparison.
The lattice angles for each albite decrease smoothly with increasing temperature; the a-axis and the volume increase smoothly with increasing temperature. The rates of change increase with increasing temperature. The c and in some cases the b-axes appear to decrease initially in the range 25–300 °C and then subsequently increase. The thermal dilatation is highly anisotropic—the change in a is about twice that in b and about six times that in c over the whole range 25–850 °C. The effect of a temperature rise on the lattice parameters of the albites is very similar to the effect of the substitution of potassium on the room-temperature parameters.
Plots of α* against γ* for each albite at a sequence of temperatures up to 950 °C fall on nearly straight parallel lines, all albites becoming less oblique (triclinic) with increasing temperature. Of the equilibrium albites, only the one synthesized at 1000°C becomes monoclinic below the melting point. The ratio d010/d001 or c*/b* is a measure of order in the albites and does not vary with temperature. The similar behaviours of this ratio and of other lattice parameters as a function of the temperature of synthesis confirms the two-step ordering process in albite.
Impaired β-cell development and insulin secretion are characteristic of intrauterine growth-restricted (IUGR) fetuses. In normally grown late gestation fetal sheep pancreatic β-cell numbers and insulin secretion are increased by 7–10 days of pulsatile hyperglycemia (PHG). Our objective was to determine if IUGR fetal sheep β-cell numbers and insulin secretion could also be increased by PHG or if IUGR fetal β-cells do not have the capacity to respond to PHG. Following chronic placental insufficiency producing IUGR in twin gestation pregnancies (n=7), fetuses were administered a PHG infusion, consisting of 60 min, high rate, pulsed infusions of dextrose three times a day with an additional continuous, low-rate infusion of dextrose to prevent a decrease in glucose concentrations between the pulses or a control saline infusion. PHG fetuses were compared with their twin IUGR fetus, which received a saline infusion for 7 days. The pulsed glucose infusion increased fetal arterial glucose concentrations an average of 83% during the infusion. Following the 7-day infusion, a square-wave fetal hyperglycemic clamp was performed in both groups to measure insulin secretion. The rate of increase in fetal insulin concentrations during the first 20 min of a square-wave hyperglycemic clamp was 44% faster in the PHG fetuses compared with saline fetuses (P<0.05). There were no differences in islet size, the insulin+ area of the pancreas and of the islets, and β-cell mass between groups (P>0.23). Chronic PHG increases early phase insulin secretion in response to acute hyperglycemia, indicating that IUGR fetal β-cells are functionally responsive to chronic PHG.