Overcoming silos in health care systems through meso-level organisations - a case study of health reforms in New South Wales, Australia.

Fragmented care delivery is a barrier to improving health system performance worldwide. Investment in meso-level organisations is a potential strategy to improve health system integration, however, its effectiveness remains unclear. In this paper, we provide an overview of key international and Australian integrated care policies. We then describe Collaborative Commissioning - a novel health reform policy to integrate primary and hospital care sectors in New South Wales (NSW), Australia and provide a case study of a model focussed on older person's care. The policy is theorised to achieve greater integration through improved governance (local stakeholders identifying as part of one health system), service delivery (communities perceive new services as preferable to status quo) and incentives (efficiency gains are reinvested locally with progressively higher value care achieved). If effectively implemented at scale, Collaborative Commissioning has potential to improve health system performance in Australia and will be of relevance to similar reform initiatives in other countries.

The genome of Roselle's flesh fly Sarcophaga ( Helicophagella) rosellei (Böttcher, 1912).

We present a genome assembly from an individual male Sarcophaga rosellei (Roselle's flesh fly; Arthropoda; Insecta; Diptera; Sarcophagidae). The genome sequence is 541 megabases in span. Most of the assembly is scaffolded into six chromosomal pseudomolecules, with the X sex chromosome assembled. The mitochondrial genome has also been assembled and is 19.5 kilobases in length. Gene annotation of this assembly on Ensembl has identified 15,437 protein coding genes.

The genome sequence of the lesser worm flesh fly, Sarcophaga ( Sarcophaga) subvicina (Baranov, 1937).

We present a genome assembly from an individual male Sarcophaga subvicina (the lesser worm flesh fly; Arthropoda; Insecta; Diptera; Sarcophagidae). The genome sequence is 71 megabases in span. Most of the assembly (95.91%) is scaffolded into six chromosomal pseudomolecules, with the X sex chromosome assembled. The mitochondrial genome has also been assembled and is 16.7 kilobases in length. Gene annotation of this assembly on Ensembl identified 16,793 protein coding genes.

The genome sequence of the Riband Wave, Idaea aversata (Linnaeus, 1758).

We present a genome assembly from an individual male Idaea aversata (the Riband Wave; Arthropoda; Insecta; Lepidoptera; Geometridae). The genome sequence is 437 megabases in span. The whole assembly is scaffolded into 30 chromosomal pseudomolecules, including the assembled Z sex chromosome. The mitochondrial genome has also been assembled and is 17.5 kilobases in length. Gene annotation of this assembly on Ensembl identified 10,165 protein coding genes.

The genome sequence of Philonthus cognatus (Stephens, 1832) (Coleoptera, Staphylinidae), a rove beetle.

We present a genome assembly from an individual male Philonthus cognatus (a rove beetle; Arthropoda; Insecta; Coleoptera; Staphylinidae). The genome sequence is 1,030.6 megabases in span. Most of the assembly is scaffolded into 12 chromosomal pseudomolecules, including the X and Y sex chromosomes. The mitochondrial genome has also been assembled and is 20.7 kilobases in length. Gene annotation of this assembly on Ensembl identified 29,629 protein coding genes.

The genome sequence of the bluish flesh fly, Sarcophaga ( Robineauella) caerulescens (Zetterstedt, 1838).

We present a genome assembly from an individual male Sarcophaga caerulescens (the bluish flesh fly; Arthropoda; Insecta; Diptera; Sarcophagidae). The genome sequence is 597 megabases in span. Most of the assembly is scaffolded into seven chromosomal pseudomolecules, including the assembled X and Y sex chromosomes. The mitochondrial genome has also been assembled and is 21.1 kilobases in length. Gene annotation of this assembly on Ensembl identified 16,559 protein coding genes.

A New Chromosome-Assigned Mongolian Gerbil Genome Allows Characterization of Complete Centromeres and a Fully Heterochromatic Chromosome.

Chromosome-scale genome assemblies based on ultralong-read sequencing technologies are able to illuminate previously intractable aspects of genome biology such as fine-scale centromere structure and large-scale variation in genome features such as heterochromatin, GC content, recombination rate, and gene content. We present here a new chromosome-scale genome of the Mongolian gerbil (Meriones unguiculatus), which includes the complete sequence of all centromeres. Gerbils are thus the one of the first vertebrates to have their centromeres completely sequenced. Gerbil centromeres are composed of four different repeats of length 6, 37, 127, or 1,747 bp, which occur in simple alternating arrays and span 1-6 Mb. Gerbil genomes have both an extensive set of GC-rich genes and chromosomes strikingly enriched for constitutive heterochromatin. We sought to determine if there was a link between these two phenomena and found that the two heterochromatic chromosomes of the Mongolian gerbil have distinct underpinnings: Chromosome 5 has a large block of intraarm heterochromatin as the result of a massive expansion of centromeric repeats, while chromosome 13 is comprised of extremely large (>150 kb) repeated sequences. In addition to characterizing centromeres, our results demonstrate the importance of including karyotypic features such as chromosome number and the locations of centromeres in the interpretation of genome sequence data and highlight novel patterns involved in the evolution of chromosomes.

The genome sequence of the Birch Marble, Apotomis betuletana (Haworth, 1811).

We present a genome assembly from an individual male Apotomis betuletana (the Birch Marble; Arthropoda; Insecta; Lepidoptera; Tortricidae). The genome sequence is 684 megabases in span. Most of the assembly is scaffolded into 28 chromosomal pseudomolecules with the Z sex chromosome assembled. The mitochondrial genome has also been assembled and is 15.8 kilobases in length. Gene annotation of this assembly on Ensembl identified 21,717 protein coding genes.

Incubation temperature alters stripe formation and head colouration in American alligator hatchlings and is unaffected by estradiol-induced sex reversal.

Considerations of the impact climate change has on reptiles are typically focused on habitat change or loss, range shifts and skewed sex ratios in species with temperature-dependent sex determination. Here, we show that incubation temperature alters stripe number and head colouration of hatchling American alligators (Alligator mississippiensis). Animals incubated at higher temperatures (33.5°C) had, on average, one more stripe than those at lower temperatures (29.5°C), and also had significantly lighter heads. These patterns were not affected by estradiol-induced sex reversal, suggesting independence from hatchling sex. Therefore, increases in nest temperatures as a result of climate change have the potential to alter pigmentation patterning, which may have implications for offspring fitness.

The genome sequence of the Common Pug, Eupithecia vulgata (Haworth, 1809).

We present a genome assembly from an individual male Eupithecia vulgata (the Common Pug; Arthropoda; Insecta; Lepidoptera; Geometridae). The genome sequence is 454.7 megabases in span. Most of the assembly is scaffolded into 31 chromosomal pseudomolecules, including the assembled Z sex chromosome. The mitochondrial genome has also been assembled and is 17.1 kilobases in length.

The genome sequence of the Six-striped Rustic, Xestia sexstrigata (Haworth, 1809).

We present a genome assembly from an individual female Xestia sexstrigata (the Six-striped Rustic; Arthropoda; Insecta; Lepidoptera; Noctuidae). The genome sequence is 638.3 megabases in span. Most of the assembly is scaffolded into 32 chromosomal pseudomolecules, including the W and Z sex chromosomes. The mitochondrial genome has also been assembled and is 15.36 kilobases in length. Gene annotation of this assembly on Ensembl identified 15,104 protein coding genes.

The genome sequence of the variegated flesh fly, Sarcophaga variegata (Scopoli, 1763).

We present a genome assembly from an individual male Sarcophaga variegata (the variegated flesh fly; Arthropoda; Insecta; Diptera; Sarcophagidae). The genome sequence is 718.5 megabases in span. Most of the assembly is scaffolded into 7 chromosomal pseudomolecules including the X and Y sex chromosomes. The mitochondrial genome has also been assembled and is 18.7 kilobases in length. Gene annotation of this assembly on Ensembl identified 16,660 protein coding genes.

Utilisation of government-subsidised chronic disease management plans and cardiovascular care in Australian general practices.

BACKGROUND: Government-subsidised general practice management plans (GPMPs) facilitate chronic disease management; however, impact on cardiovascular disease (CVD) is unknown. We aimed to determine utilisation and impact of GPMPs for people with or at elevated risk of CVD. METHODS: Secondary analysis of baseline data from the CONNECT randomised controlled trial linked to Medicare Benefits Schedule (MBS) and Pharmaceutical Benefits Scheme (PBS) claims. Multivariate regression examining the association of GPMP receipt and review with: (1) ≥ 1 MBS-subsidised allied health visit in the previous 24 months; (2) adherence to dual cardioprotective medication (≥ 80% of days covered with a dispensed PBS prescription); and (3) meeting recommended LDL-cholesterol and blood pressure (BP) targets concurrently. RESULTS: Overall, 905 trial participants from 24 primary health care services consented to data linkage. Participants with a GPMP (46.6%, 422/905) were older (69.4 vs 66.0 years), had lower education (32.3% vs 24.7% high school or lower), lower household income (27.5% vs 17.0% in lowest bracket), and more comorbidities, particularly diabetes (42.2% vs 17.6%) compared to those without a GPMP. After adjustment, a GPMP was strongly associated with allied health visits (odds ratio (OR) 14.80, 95% CI: 9.08-24.11) but not higher medication adherence rates (OR 0.82, 95% CI: 0.52-1.29) nor meeting combined LDL and BP targets (OR 1.31, 95% CI: 0.72-2.38). Minor differences in significant covariates were noted in models using GPMP review versus GPMP initiation. CONCLUSIONS: In people with or at elevated risk of CVD, GPMPs are under-utilised overall. They are targeting high-needs populations and facilitate allied health access, but are not associated with improved CVD risk management, which represents an opportunity for enhancing their value in supporting guideline-recommended care.

Regulation of posterior Hox genes by sex steroids explains vertebral variation in inbred mouse strains.

A series of elegant embryo transfer experiments in the 1950s demonstrated that the uterine environment could alter vertebral patterning in inbred mouse strains. In the intervening decades, attention has tended to focus on the technical achievements involved and neglected the underlying biological question: how can genetically homogenous individuals have a heterogenous number of vertebrae? Here I revisit these experiments and, with the benefit of knowledge of the molecular-level processes of vertebral patterning gained over the intervening decades, suggest a novel hypothesis for homeotic transformation of the last lumbar vertebra to the adjacent sacral type through regulation of Hox genes by sex steroids. Hox genes are involved in both axial patterning and development of male and female reproductive systems and have been shown to be sensitive to sex steroids in vitro and in vivo. Regulation of these genes by sex steroids and resulting alterations to vertebral patterning may hint at a deep evolutionary link between the ribless lumbar region of mammals and the switch from egg-laying to embryo implantation. An appreciation of the impact of sex steroids on Hox genes may explain some puzzling aspects of human disease, and highlights the spine as a neglected target for in utero exposure to endocrine disruptors.

The genome sequence of the hawthorn shieldbug, Acanthosoma haemorrhoidale (Linnaeus, 1758).

We present a genome assembly from an individual male Acanthosoma haemorrhoidale (hawthorn shieldbug; Arthropoda; Insecta; Hemiptera; Acanthosomatidae). The genome sequence is 866 megabases in span. The majority of the assembly (99.98%) is scaffolded into 7 chromosomal pseudomolecules with the X and Y sex chromosomes assembled. The complete mitochondrial genome was also assembled and is 18.9 kilobases in length.

An Internet-Based Intervention for Cardiovascular Disease Management Integrated With Primary Care Electronic Health Records: Mixed Methods Evaluation of Implementation Fidelity and User Engagement.

BACKGROUND: Growing evidence supports the benefits of eHealth interventions to increase patient engagement and improve outcomes for a range of conditions. However, ineffective program delivery and usage attrition limit exposure to these interventions and may reduce their effectiveness. OBJECTIVE: This study aims to evaluate the delivery fidelity of an eHealth intervention, describe use patterns, compare outcomes between low and high users, and identify mediating factors on intervention delivery and receipt. METHODS: This is a mixed methods study of an internet-based intervention being evaluated for effectiveness in a randomized controlled trial (RCT). The intervention comprised medication and cardiovascular disease (CVD) risk data uploaded from the primary care electronic health record (EHR); interactive, personalized CVD risk score estimation; goal setting and self-monitoring; an interactive social forum; and optional receipt of heart health messages. Fidelity was assessed over 12 months. Trial outcomes were compared between low and high users. Data sources included program delivery records, web log data, trial data, and thematic analysis of communication records. RESULTS: Most participants in the intervention group (451/486, 93%) had an initial training session conducted by telephone (413/447, 92.4% of participants trained), with a mean duration of 44 minutes (range 10-90 minutes). Staff conducted 98.45% (1776/1804) of the expected follow-ups, mostly by telephone or email. Of the 451 participants who commenced log-ins, 46.8% (211) were categorized as low users (defined as at least one log-in in 3 or fewer months of follow-up), 40.4% (182) were categorized as high users (at least one log-in in more than 3 months of follow-up), and 12.8% (58) were nonadopters (no log-ins after their training session). The mean log-in frequency was 3-4 per month in ongoing users. There was no significant difference between the groups in the primary trial outcome of adherence to guideline-recommended medications (P=.44). In unadjusted analyses, high users had significantly greater eHealth literacy scores (P=.003) and were more likely to meet recommended weekly targets for fruit (P=.03) and fish (P=.004) servings; however, the adjusted findings were not significant. Interactive screen use was highest for goal tracking and lowest for the chat forum. Screens with EHR-derived data held only an early interest for most users. Fidelity measures (reach, content, dose delivered, and dose received) were influenced by the facilitation strategies used by staff, invisible qualities of staff-participant communication, and participants' responsiveness to intervention attributes. CONCLUSIONS: A multifeature internet-based intervention was delivered with high fidelity to the RCT protocol and was regularly used by 40.4% (182/451) of users over 12 months. Higher log-in frequency as an indicator of greater intervention exposure was not associated with statistically significant improvements in eHealth literacy scores, lifestyle changes, or clinical outcomes. Attributes of the intervention and individualized support influenced initial and ongoing use.

A digital health intervention for cardiovascular disease management in primary care (CONNECT) randomized controlled trial.

Digital health applications (apps) have the potential to improve health behaviors and outcomes. We aimed to examine the effectiveness of a consumer web-based app linked to primary care electronic health records (EHRs). CONNECT was a multicenter randomized controlled trial involving patients with or at risk of cardiovascular disease (CVD) recruited from primary care (Clinical Trial registration ACTRN12613000715774). Intervention participants received an interactive app which was pre-populated and refreshed with EHR risk factor data, diagnoses and, medications. Interactive risk calculators, motivational messages and lifestyle goal tracking were also included. Control group received usual health care. Primary outcome was adherence to guideline-recommended medications (≥80% of days covered for blood pressure (BP) and statin medications). Secondary outcomes included attainment of risk factor targets and eHealth literacy. In total, 934 patients were recruited; mean age 67.6 (±8.1) years. At 12 months, the proportion with >80% days covered with recommended medicines was low overall and there was no difference between the groups (32.8% vs. 29.9%; relative risk [RR] 1.07 [95% CI, 0.88-1.20] p = 0.49). There was borderline improvement in the proportion meeting BP and LDL targets in intervention vs. control (17.1% vs. 12.1% RR 1.40 [95% CI, 0.97-2.03] p = 0.07). The intervention was associated with increased attainment of physical activity targets (87.0% intervention vs. 79.7% control, p = 0.02) and e-health literacy scores (72.6% intervention vs. 64.0% control, p = 0.02). In conclusion, a consumer app integrated with primary health care EHRs was not effective in increasing medication adherence. Borderline improvements in risk factors and modest behavior changes were observed.

Runaway GC Evolution in Gerbil Genomes.

Recombination increases the local GC-content in genomic regions through GC-biased gene conversion (gBGC). The recent discovery of a large genomic region with extreme GC-content in the fat sand rat Psammomys obesus provides a model to study the effects of gBGC on chromosome evolution. Here, we compare the GC-content and GC-to-AT substitution patterns across protein-coding genes of four gerbil species and two murine rodents (mouse and rat). We find that the known high-GC region is present in all the gerbils, and is characterized by high substitution rates for all mutational categories (AT-to-GC, GC-to-AT, and GC-conservative) both at synonymous and nonsynonymous sites. A higher AT-to-GC than GC-to-AT rate is consistent with the high GC-content. Additionally, we find more than 300 genes outside the known region with outlying values of AT-to-GC synonymous substitution rates in gerbils. Of these, over 30% are organized into at least 17 large clusters observable at the megabase-scale. The unusual GC-skewed substitution pattern suggests the evolution of genomic regions with very high recombination rates in the gerbil lineage, which can lead to a runaway increase in GC-content. Our results imply that rapid evolution of GC-content is possible in mammals, with gerbil species providing a powerful model to study the mechanisms of gBGC.

Greater Loss of Female Embryos During Human Pregnancy: A Novel Mechanism.

Given an equal sex ratio at conception, the excess of human males at birth can only be explained by greater loss of females during pregnancy. It is proposed that the bias against females during human development is the result of a greater degree of genetic and metabolic "differentness" between female embryos and maternal tissues than for similarly aged males, and that successful implantation and placentation represents a threshold dichotomy, where the acceptance threshold shifts depending on maternal condition, especially stress. Right and left ovaries are not equal, and neither are the eggs and follicular fluid that they produce, and it is further hypothesized that during times of stress, the implantation threshold is shifted sufficiently to favor survival of females, most likely those originating from the right ovary, and that this, rather than simply a greater loss of males, explains at least some of the variability in the human sex ratio at birth.