Hospitalizations from Birth to 28 Years in a Population Cohort of Individuals Born with Five Rare Craniofacial Anomalies in Western Australia.

OBJECTIVE: To describe trends, age-specific patterns, and factors influencing hospitalizations for 5 rare craniofacial anomalies (CFAs). METHODS: Data on livebirths (1983-2010; n = 721 019) including rare CFA (craniofacial microsomia, mandibulofacial dysostosis, Pierre Robin sequence, Van der Woude syndrome, and frontonasal dysplasia), episodes of death, and demographic and perinatal factors were identified from the Western Australian Register of Developmental Anomalies, Death Registrations and Midwives Notification System. Information on incident craniofacial and noncraniofacial related admissions, length of hospital stay, and intensive care and emergency-related admissions were identified using principal diagnosis and procedural codes were extracted from the Hospital Morbidity Data Collection and linked to other data sources. Associations of hospitalizations by age groups as well as demographic and perinatal factors were expressed as incidence rate ratio (IRR). RESULTS: The incident hospitalizations were 3 times as high for rare CFA (IRR 3.22-3.72) throughout childhood into adolescence than those without. Children with rare CFA had 3-4 times as many potentially preventable hospitalizations until 18 years of age than those without. Specifically, respiratory infections (IRR 2.13-2.35), ear infections (IRR 7.92-26.28), and oral health-related conditions contributed for most noncraniofacial admissions until the adolescence period. A greater incidence of noncraniofacial related hospitalizations was observed among Indigenous children, births with intrauterine growth restrictions, and families with high socioeconomic disadvantage. CONCLUSIONS: Throughout childhood, individuals with rare CFA had greater hospital service use, specifically for potentially preventable conditions, than those without. These population-level findings can inform new preventive strategies and early disease management targeted toward reducing preventable hospitalizations.

Patterns, trends, and factors influencing hospitalizations for craniosynostosis in Western Australia. A population-based study.

Understanding hospital service use among children with a diagnosis of craniosynostosis (CS) is important to improve services and outcomes. This study aimed to describe population-level trends, patterns, and factors influencing hospitalizations for craniosynostosis in Western Australia. Data on live births (1990-2010; n = 554,624) including craniosynostosis, episodes of death, demographic, and perinatal factors were identified from the midwives, birth defects, hospitalizations, and death datasets. Information on craniosynostosis and non-craniosynostosis-related admissions, cumulative length of hospital stay (cLoS), intensive care unit, and emergency department-related admissions were extracted from the hospitalization dataset and linked to other data sources. These associations were examined using negative binomial regression presented as annual percent change and associations of hospitalizations by age groups, demographic, and perinatal factors were expressed as incidence rate ratio (IRR). We found an increasing trend in incident hospitalizations but a marginal decline in cLoS for craniosynostosis over the observed study period. Perinatal conditions, feeding difficulties, nervous system anomalies, respiratory, and other infections contributed to majority of infant non-CS-related admissions.Respiratory infections accounted for about twice the number of admissions for individuals with CS (IRRs 1.94-2.34) across all observed age groups. Higher incidence of non-CS hospitalizations was observed among females, with associated anomalies, to families with highest socioeconomic disadvantage and living in remote areas of the state.   Conclusion: Marginal reduction in the cLoS for CS-related admissions observed over the 21-year period are potentially indicative of improved peri-operative care. However, higher incidence of respiratory infection-related admissions for syndromic synostosis is concerning and requires investigation.

Epidemiology of Hospital Admissions for Craniosynostosis in Australia: A Population-Based Study.

To describe trends, age, and sex-specific patterns of population hospital admissions with a diagnosis of craniosynostosis (CS) in Australia.Population data for hospital separations (in-patient) from public and private hospitals (July 1996-June 2018) were obtained from the publicly available Australian Institute of Health and Welfare (AIHW) National Hospital Morbidity Database.The outcome variables were hospital separation rates (HSR) (number of hospital separations divided by the estimated resident population [ERP] per year) and average length of stay (aLOS) (patient days divided by the number of hospital separations) with a diagnosis of CS. Trends in HSR and aLOS adjusted for age, sex, and type of CS were investigated by negative binomial regression presented as annual percent change (APC).In 8057 admissions identified, we observed no significant change in the annual trend for HSR for the 22-year period. However, a marginal annual decrease of 1.6% (95% CI: -0.7, -2.4) in the aLOS was identified for the same time period. HSR were higher for males, infants, and single suture synostosis. aLOS was 3.8 days (95% CI: 3.8, 3.9) per visit, longer for syndromic conditions.There was a minor reduction in the average length of hospital stay for CS over the 22-year period potentially indicative of improved care. Population-level information on hospitalisations for rare craniofacial conditions can inform research, clinical, and surgical practice.

Haplotype variants of the stripe rust resistance gene Yr28 in Aegilops tauschii.

KEY MESSAGE: Stripe rust resistance gene YrAet672 from Aegilops tauschii accession CPI110672 encodes a nucleotide-binding and leucine-rich repeat domain containing protein similar to YrAS2388 and both these members were haplotypes of Yr28. New sources of host resistance are required to counter the continued emergence of new pathotypes of the wheat stripe rust pathogen Puccinia striiformis Westend. f. sp. tritici Erikss. (Pst). Here, we show that CPI110672, an Aegilops tauschii accession from Turkmenistan, carries a single Pst resistance gene, YrAet672, that is effective against multiple Pst pathotypes, including the four predominant Pst lineages present in Australia. The YRAet672 locus was fine mapped to the short arm of chromosome 4D, and a nucleotide-binding and leucine-rich repeat gene was identified at the locus. A transgene encoding the YrAet672 genomic sequence, but lacking a copy of a duplicated sequence present in the 3' UTR, was transformed into wheat cultivar Fielder and Avocet S. This transgene conferred a weak resistance response, suggesting that the duplicated 3' UTR region was essential for function. Subsequent analyses demonstrated that YrAet672 is the same as two other Pst resistance genes described in Ae. tauschii, namely YrAS2388 and Yr28. They were identified as haplotypes encoding identical protein sequences but are polymorphic in non-translated regions of the gene. Suppression of resistance conferred by YrAet672 and Yr28 in synthetic hexaploid wheat lines (AABBDD) involving Langdon (AABB) as the tetraploid parent was associated with a reduction in transcript accumulation.

Description of Total Population Hospital Admissions for Treacher Collins Syndrome in Australia.

OBJECTIVE: To describe patterns and demographic characteristics of total-population hospital admissions with a diagnosis of Treacher Collins syndrome (TCS) in Australia. DATA SOURCE: Population summary data for inpatient hospitals admissions (public and private) with a principal diagnosis of TCS (ICD10-AM-Q87.04) were obtained from the Australian Institute of Health and Welfare National Hospital Morbidity Database for a 11-year period (2002-2013). MAIN OUTCOME MEASURES: The primary outcome was hospital separation rate (HSR), calculated by dividing the number of hospital separations by estimated resident population per year. Trends in HSR s adjusted for age and sex were investigated by negative binomial regression presented as annual percent change and the association of rates with age and sex was expressed as incidence rate ratio. RESULTS: In 244 admissions identified, we observed an increase of 4.55% (95% confidence interval [CI] -1.78, 11.29) in HSR's over the 11-year period. Rates were higher during infancy (1.87 [95% CI 1.42, 2.42]), declining markedly with increasing age. The average length of hospital stay was 6.09 days (95% CI 5.78, 6.40) per episode, but longer for females and infants. CONCLUSIONS: Findings indicate an increase in hospitalization rates, especially among infants and females which potentially relates to early airway intervention procedures possibly influenced by sex specific-disease severity and phenotypic variability of TCS. Awareness of the TCS phenotype and improved access to genetic testing may support more personalized and efficient care. Total-population administrative data offers a potential to better understand the health burden of rare craniofacial diseases.

A recombined Sr26 and Sr61 disease resistance gene stack in wheat encodes unrelated NLR genes.

The re-emergence of stem rust on wheat in Europe and Africa is reinforcing the ongoing need for durable resistance gene deployment. Here, we isolate from wheat, Sr26 and Sr61, with both genes independently introduced as alien chromosome introgressions from tall wheat grass (Thinopyrum ponticum). Mutational genomics and targeted exome capture identify Sr26 and Sr61 as separate single genes that encode unrelated (34.8%) nucleotide binding site leucine rich repeat proteins. Sr26 and Sr61 are each validated by transgenic complementation using endogenous and/or heterologous promoter sequences. Sr61 orthologs are absent from current Thinopyrum elongatum and wheat pan genome sequences, contrasting with Sr26 where homologues are present. Using gene-specific markers, we validate the presence of both genes on a single recombinant alien segment developed in wheat. The co-location of these genes on a small non-recombinogenic segment simplifies their deployment as a gene stack and potentially enhances their resistance durability.

Current Management of Extraperitoneal Bladder Injuries: Results from the Multi-Institutional Genito-Urinary Trauma Study (MiGUTS).

PURPOSE: We studied the current management trends for extraperitoneal bladder injuries and evaluated the use of operative repair versus catheter drainage, and the associated complications with each approach. MATERIALS AND METHODS: We prospectively collected data on bladder trauma from 20 level 1 trauma centers across the United States from 2013 to 2018. We excluded patients with intraperitoneal bladder injury and those who died within 24 hours of hospital arrival. We separated patients with extraperitoneal bladder injuries into 2 groups (catheter drainage vs operative repair) based on their initial management within the first 4 days and compared the rates of bladder injury related complications among them. Regression analyses were used to identify potential predictors of complications. RESULTS: From 323 bladder injuries we included 157 patients with extraperitoneal bladder injuries. Concomitant injuries occurred in 139 (88%) patients with pelvic fracture seen in 79%. Sixty-seven patients (43%) initially underwent operative repair for their extraperitoneal bladder injuries. The 3 most common reasons for operative repair were severity of injury or bladder neck injury (40%), injury found during laparotomy (39%) and concern for pelvic hardware contamination (28%). Significant complications were identified in 23% and 19% of the catheter drainage and operative repair groups, respectively (p=0.55). The only statistically significant predictor for complications was bladder neck or urethral injury (RR 2.69, 95% 1.21-5.97, p=0.01). CONCLUSIONS: In this large multi-institutional cohort, 43% of patients underwent surgical repair for initial management of extraperitoneal bladder injuries. We found no significant difference in complications between the initial management strategies of catheter drainage and operative repair. The most significant predictor for complications was concomitant urethral or bladder neck injury.

The American Association for the Surgery of Trauma renal injury grading scale: Implications of the 2018 revisions for injury reclassification and predicting bleeding interventions.

BACKGROUND: In 2018, the American Association for the Surgery of Trauma (AAST) published revisions to the renal injury grading system to reflect the increased reliance on computed tomography scans and non-operative management of high-grade renal trauma (HGRT). We aimed to evaluate how these revisions will change the grading of HGRT and if it outperforms the original 1989 grading in predicting bleeding control interventions. METHODS: Data on HGRT were collected from 14 Level-1 trauma centers from 2014 to 2017. Patients with initial computed tomography scans were included. Two radiologists reviewed the scans to regrade the injuries according to the 1989 and 2018 AAST grading systems. Descriptive statistics were used to assess grade reclassifications. Mixed-effect multivariable logistic regression was used to measure the predictive ability of each grading system. The areas under the curves were compared. RESULTS: Of the 322 injuries included, 27.0% were upgraded, 3.4% were downgraded, and 69.5% remained unchanged. Of the injuries graded as III or lower using the 1989 AAST, 33.5% were upgraded to grade IV using the 2018 AAST. Of the grade V injuries, 58.8% were downgraded using the 2018 AAST. There was no statistically significant difference in the overall areas under the curves between the 2018 and 1989 AAST grading system for predicting bleeding interventions (0.72 vs. 0.68, p = 0.34). CONCLUSION: About one third of the injuries previously classified as grade III will be upgraded to grade IV using the 2018 AAST, which adds to the heterogeneity of grade IV injuries. Although the 2018 AAST grading provides more anatomic details on injury patterns and includes important radiologic findings, it did not outperform the 1989 AAST grading in predicting bleeding interventions. LEVEL OF EVIDENCE: Prognostic and Epidemiological Study, level III.

The associations between initial radiographic findings and interventions for renal hemorrhage after high-grade renal trauma: Results from the Multi-Institutional Genitourinary Trauma Study.

BACKGROUND: Indications for intervention after high-grade renal trauma (HGRT) remain poorly defined. Certain radiographic findings can be used to guide the management of HGRT. We aimed to assess the associations between initial radiographic findings and interventions for hemorrhage after HGRT and to determine hematoma and laceration sizes predicting interventions. METHODS: The Genitourinary Trauma Study is a multicenter study including HGRT patients from 14 Level I trauma centers from 2014 to 2017. Admission computed tomography scans were categorized based on multiple variables, including vascular contrast extravasation (VCE), hematoma rim distance (HRD), and size of the deepest laceration. Renal bleeding interventions included angioembolization, surgical packing, renorrhaphy, partial nephrectomy, and nephrectomy. Mixed-effect Poisson regression was used to assess the associations. Receiver operating characteristic analysis was used to define optimal cutoffs for HRD and laceration size. RESULTS: In the 326 patients, injury mechanism was blunt in 81%. Forty-seven (14%) patients underwent 51 bleeding interventions, including 19 renal angioembolizations, 16 nephrectomies, and 16 other procedures. In univariable analysis, presence of VCE was associated with a 5.9-fold increase in risk of interventions, and each centimeter increase in HRD was associated with 30% increase in risk of bleeding interventions. An HRD of 3.5 cm or greater and renal laceration depth of 2.5 cm or greater were most predictive of interventions. In multivariable models, VCE and HRD were significantly associated with bleeding interventions. CONCLUSION: Our findings support the importance of certain radiographic findings in prediction of bleeding interventions after HGRT. These factors can be used as adjuncts to renal injury grading to guide clinical decision making. LEVEL OF EVIDENCE: Prognostic and Epidemiological Study, Level III and Therapeutic/Care Management, Level IV.

A nomogram predicting the need for bleeding interventions after high-grade renal trauma: Results from the American Association for the Surgery of Trauma Multi-institutional Genito-Urinary Trauma Study (MiGUTS).

BACKGROUND: The management of high-grade renal trauma (HGRT) and the indications for intervention are not well defined. The American Association for the Surgery of Trauma (AAST) renal grading does not incorporate some important clinical and radiologic variables associated with increased risk of interventions. We aimed to use data from a multi-institutional contemporary cohort to develop a nomogram predicting risk of interventions for bleeding after HGRT. METHODS: From 2014 to 2017, data on adult HGRT (AAST grades III-V) were collected from 14 level 1 trauma centers. Patients with both clinical and radiologic data were included. Data were gathered on demographics, injury characteristics, management, and outcomes. Clinical and radiologic parameters, obtained after trauma evaluation, were used to predict renal bleeding interventions. We developed a prediction model by applying backward model selection to a logistic regression model and built a nomogram using the selected model. RESULTS: A total of 326 patients met the inclusion criteria. Mechanism of injury was blunt in 81%. Median age and injury severity score were 28 years and 22, respectively. Injuries were reported as AAST grades III (60%), IV (33%), and V (7%). Overall, 47 (14%) underwent interventions for bleeding control including 19 renal angioembolizations, 16 nephrectomies, and 12 other procedures. Of the variables included in the nomogram, a hematoma size of 12 cm contributed the most points, followed by penetrating trauma mechanism, vascular contrast extravasation, pararenal hematoma extension, concomitant injuries, and shock. The area under the receiver operating characteristic curve was 0.83 (95% confidence interval, 0.81-0.85). CONCLUSION: We developed a nomogram that integrates multiple clinical and radiologic factors readily available upon assessment of patients with HGRT and can provide predicted probability for bleeding interventions. This nomogram may help in guiding appropriate management of HGRT and decreasing unnecessary interventions. LEVEL OF EVIDENCE: Prognostic and epidemiological study, level III.

Optimal timing of delayed excretory phase computed tomography scan for diagnosis of urinary extravasation after high-grade renal trauma.

BACKGROUND: Excretory phase computed tomography (CT) scan is used for diagnosis of renal collecting system injuries and accurate grading of high-grade renal trauma. However, optimal timing of the excretory phase is not well established. We hypothesized that there is an association between excretory phase timing and diagnosis of urinary extravasation and aimed to identify the optimal excretory phase timing for diagnosis of urinary extravasation. METHODS: The Genito-Urinary Trauma Study collected data on high-grade renal trauma (grades III-V) from 14 Level I trauma centers between 2014 and 2017. The time between portal venous and excretory phases at initial CT scans was recorded. Poisson regression was used to measure the association between excretory phase timing and diagnosis of urinary extravasation. Predictive receiver operating characteristic analysis was used to identify a cutoff point optimizing detection of urinary extravasation. RESULTS: Overall, 326 patients were included; 245 (75%) had excretory phase CT scans for review either initially (n = 212) or only at their follow-up (n = 33). At initial CT with excretory phase, 46 (22%) of 212 patients were diagnosed with urinary extravasation. Median time between portal venous and excretory phases was 4 minutes (interquartile range, 4-7 minutes). Time of initial excretory phase was significantly greater in those diagnosed with urinary extravasation. Increased time to excretory phase was positively associated with finding urinary extravasation at the initial CT scan after controlling for multiple factors (risk ratio per minute, 1.15; 95% confidence interval, 1.09-1.22; p < 0.001). The optimal delay for detection of urinary extravasation was 9 minutes. CONCLUSION: Timing of the excretory phase is a significant factor in accurate diagnosis of renal collecting system injury. A 9-minute delay between the early and excretory phases optimized detection of urinary extravasation. LEVEL OF EVIDENCE: Diagnostic tests/criteria study, level III.

Gender-affirming hormones and surgery in transgender children and adolescents.

The Endocrine Society Clinical Practice Guidelines on the treatment of gender incongruent people recommend the use of gender-affirming cross-sex hormone (CSH) interventions in transgender children and adolescents who request this treatment, who have undergone psychiatric assessment, and have maintained a persistent transgender identity. The intervention can help to affirm gender identity by inducing masculine or feminine physical characteristics that are congruent with an individual's gender expression, while aiming to improve mental health and quality-of-life outcomes. Some transgender individuals might also wish to access gender-affirming surgeries during adolescence; however, research to inform best clinical practice for surgeons and other medical professionals is scarce. This Review explores the available published evidence on gender-affirming CSH and surgical interventions in transgender children and adolescents, amalgamating findings on mental health outcomes, cognitive and physical effects, side-effects, and safety variables. The small amount of available data suggest that when clearly indicated in accordance with international guidelines, gender-affirming CSHs and chest wall masculinisation in transgender males are associated with improvements in mental health and quality of life. Evidence regarding surgical vaginoplasty in transgender females younger than age 18 years remains extremely scarce and conclusions cannot yet be drawn regarding its risks and benefits in this age group. Further research on an international scale is urgently warranted to clarify long-term outcomes on psychological functioning and safety.

A strategy for identifying markers linked with stem rust resistance in wheat harbouring an alien chromosome introgression from a non-sequenced genome.

KEY MESSAGE: A set of molecular markers was developed for Sr26 from comparative genomic analysis. The comparative genomic approach also enabled the identification of a previously uncharacterised wheat chromosome that carried Sr26. Stem rust of wheat, a biotic stress caused by a fungal pathogen, continues to pose significant threats to wheat production. Considerable effort has been directed at surveillance and breeding approaches to minimize the impact of the widely virulent race of the stem rust pathogen (Puccinia graminis f. sp. tritici, Pgt) commonly known as Ug99 (TTKSK) and other races in its lineage. The stem rust resistance gene Sr26, derived from Thinopyrum ponticum, is an excellent example of the successful utilization of a gene from a wild relative of a crop plant and remains one of the few durable sources of resistance currently effective against all known field isolates of Pgt. We explored comparative genomic analysis of the nucleotide binding leucine rich repeat (NLR) genes of the diploid D genome and bread wheat genomes to target the Sr26 region from the non-sequenced Th. ponticum genome. A chromosomal interval harboring NLR genes in the distal end of homoeologous group 6 chromosomes was used to demarcate the Sr26 locus. A set of closely linked PCR-based molecular markers was developed for Sr26. Furthermore, the comparative analysis approach enabled the unambiguous identification of a previously uncharacterised wheat chromosome that carried Sr26 in an introgressed Th. ponticum segment and was validated by fluorescent and genomic in situ hybridisation (FISH/GISH) experiments. The genetic information generated from the target interval based on this study will benefit future related studies on group 6 chromosomes of wheat, including 6Dt from Aegilops tauschii, and chromosome 6Ae#1 from Th. ponticum.

Exploring Racial Differences Surrounding Prostate Cancer Screening: Beliefs and Attitudes in Community Dwelling Men Attending an Urban Men's Health Event.

The purpose of the study was to explore attitudes/beliefs in men attending an urban health fair to explore barriers to prostate cancer (PCa) screening. Five hundred and forty-four men attending the PCa booth at the fair in 2014 or 2015 completed questionnaires about PCa. Data were examined using Pearson's χ2, Fisher's Exact, and Wilcoxon rank tests after grouping men by African American (AA) and non-African American ethnicity. Three hundred and twenty-six (60%) men were AA and two hundred and eighteen (40%) were non-AA (89% white). Median age (54 vs. 56 years) and prior PCa screening were similar between AA and non-AA; income ( p = .044) and education ( p = .0002) differed. AA men were less likely to have researched prostate-specific antigen (PSA) on the internet ( p = .003), but more used TV ( p = .003) and media ( p = .0014) as information sources. Family members had a stronger influence over screening decisions for AA men ( p = .005). After reading PSA information, AA men were more likely to still be confused ( p = .008). A higher proportion of AA men were less worried about dying from PCa ( p = .0006), but would want treatment immediately instead of watchful waiting ( p < .0001). Interestingly, a higher proportion of AA men indicated that they would prefer not to know if they had PCa ( p = .001). Ultimately, more AA men had a PSA done (98.4% vs. 95.1%; p = .031). When considering screening eligible men, a higher proportion of AA men had an abnormal PSA (13.1% vs. 5.3%; p = .037). AA men's beliefs surrounding PCa differ from non-AA men, and should be considered when developing culturally appropriate education, screening, and treatment strategies for this group.

Contemporary management of high-grade renal trauma: Results from the American Association for the Surgery of Trauma Genitourinary Trauma study.

BACKGROUND: The rarity of renal trauma limits its study and the strength of evidence-based guidelines. Although management of renal injuries has shifted toward a nonoperative approach, nephrectomy remains the most common intervention for high-grade renal trauma (HGRT). We aimed to describe the contemporary management of HGRT in the United States and also evaluate clinical factors associated with nephrectomy after HGRT. METHODS: From 2014 to 2017, data on HGRT (American Association for the Surgery of Trauma grades III-V) were collected from 14 participating Level-1 trauma centers. Data were gathered on demographics, injury characteristics, management, and short-term outcomes. Management was classified into three groups-expectant, conservative/minimally invasive, and open operative. Descriptive statistics were used to report management of renal trauma. Univariate and multivariate logistic mixed effect models with clustering by facility were used to look at associations between proposed risk factors and nephrectomy. RESULTS: A total of 431 adult HGRT were recorded; 79% were male, and mechanism of injury was blunt in 71%. Injuries were graded as III, IV, and V in 236 (55%), 142 (33%), and 53 (12%), respectively. Laparotomy was performed in 169 (39%) patients. Overall, 300 (70%) patients were managed expectantly and 47 (11%) underwent conservative/minimally invasive management. Eighty-four (19%) underwent renal-related open operative management with 55 (67%) of them undergoing nephrectomy. Nephrectomy rates were 15% and 62% for grades IV and V, respectively. Penetrating injuries had significantly higher American Association for the Surgery of Trauma grades and higher rates of nephrectomy. In multivariable analysis, only renal injury grade and penetrating mechanism of injury were significantly associated with undergoing nephrectomy. CONCLUSION: Expectant and conservative management is currently utilized in 80% of HGRT; however, the rate of nephrectomy remains high. Clinical factors, such as surrogates of hemodynamic instability and metabolic acidosis, are associated with nephrectomy for HGRT; however, higher renal injury grade and penetrating trauma remain the strongest associations. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III; Therapeutic study, level IV.

Establishment of Photosynthesis through Chloroplast Development Is Controlled by Two Distinct Regulatory Phases.

Chloroplasts develop from undifferentiated proplastids present in meristematic tissue. Thus, chloroplast biogenesis is closely connected to leaf development, which restricts our ability to study the process of chloroplast biogenesis per se. As a consequence, we know relatively little about the regulatory mechanisms behind the establishment of the photosynthetic reactions and how the activities of the two genomes involved are coordinated during chloroplast development. We developed a single cell-based experimental system from Arabidopsis (Arabidopsis thaliana) with high temporal resolution allowing for investigations of the transition from proplastids to functional chloroplasts. Using this unique cell line, we could show that the establishment of photosynthesis is dependent on a regulatory mechanism involving two distinct phases. The first phase is triggered by rapid light-induced changes in gene expression and the metabolome. The second phase is dependent on the activation of the chloroplast and generates massive changes in the nuclear gene expression required for the transition to photosynthetically functional chloroplasts. The second phase also is associated with a spatial transition of the chloroplasts from clusters around the nucleus to the final position at the cell cortex. Thus, the establishment of photosynthesis is a two-phase process with a clear checkpoint associated with the second regulatory phase allowing coordination of the activities of the nuclear and plastid genomes.

APOE ε4 moderates abnormal CSF-abeta-42 levels, while neurocognitive impairment is associated with abnormal CSF tau levels in HIV+ individuals - a cross-sectional observational study.

BACKGROUND: Cerebrospinal fluid (CSF) biomarkers Aß1-42, t-tau and p-tau have a characteristic pattern in Alzheimer's Disease (AD). Their roles in HIV-associated neurocognitive disorder (HAND) remains unclear. METHODS: Adults with chronic treated HIV disease were recruited (n = 43, aged 56.7 ± 7.9; 32% aged 60+; median HIV duration 20 years, >95% plasma and CSF HIV RNA <50 cp/mL, on cART for a median 24 months). All underwent standard neuropsychological testing (61% had HAND), APOE genotyping (30.9% carried APOE ε4 and 7.1% were ε4 homozygotes) and a lumbar puncture. Concentrations of Aß1-42, t-tau and p-tau were assessed in the CSF using commercial ELISAs. Current neurocognitive status was defined using the continuous Global Deficit Score, which grades impairment in clinically relevant categories. History of HAND was recorded. Univariate correlations informed multivariate models, which were corrected for nadir CD4-T cell counts and HIV duration. RESULTS: Carriage of APOE ε4 predicted markedly lower levels of CSF Aß1-42 in univariate (r = -.50; p = .001) and multivariate analyses (R(2) = .25; p < .0003). Greater levels of neurocognitive impairment were associated with higher CSF levels of p-tau in univariate analyses (r = .32; p = .03) and multivariate analyses (R(2) = .10; p = .03). AD risk prediction cut-offs incorporating all three CSF biomarkers suggested that 12.5% of participants had a high risk for AD. Having a CSF-AD like profile was more frequent in those with current (p = .05) and past HIV-associated dementia (p = .03). CONCLUSIONS: Similarly to larger studies, APOE ε4 genotype was not directly associated with HAND, but moderated CSF levels of Aß1-42 in a minority of participants. In the majority of participants, increased CSF p-tau levels were associated with current neurocognitive impairment. Combined CSF biomarker risk for AD in the current HIV+ sample is more than 10 times greater than in the Australian population of the same age. Larger prospective studies are warranted.

Acute coronary syndrome in Australia: Where are we now and where are we going?

BACKGROUND: Acute coronary syndrome (ACS) is a significant contributor to both morbidity and mortality in Australia. Generally speaking, sufferers of ACS who live in rural areas and are treated at rural hospitals have poorer outcomes than those living in metropolitan areas. AIMS: To characterise the differences in the management and outcomes of rural and metropolitan populations in the context of ACS, as well as identify factors responsible for these differences and suggest how they may be addressed. METHOD: A review of the current literature surrounding ACS in Australia was undertaken. Through the MEDLINE/PubMed database a thorough search using the terms "acute coronary syndrome" and "Australia" identified 460 papers for review, excluding abstracts and adding "rural", "metropolitan", "reperfusion", and "outcomes" to this search narrowed the results to 149 papers for review. Data was also extracted from the Australian Institute of Health and Welfare and other Australian government publications. The review draws on insights from both local and international resources and seeks to provide an understanding of the contemporary landscape of ACS in both rural and metropolitan Australia. The review is broken down into three key sections: An outline of the 2011 National Heart Foundation of Australia/Cardiac Society of Australia and New Zealand (NHF/CSANZ) guidelines and adjuvant tools used in the assessment and treatment of ACS, and to what extent these guidelines have been implemented clinically.An exploration of the current landscape of ACS in Australia and identification of the disparities facing rural populations compared to those in metropolitan areas.Discussion of the factors that are resulting in poorer outcomes for ACS sufferers and suggestions of novel approaches towards addressing these factors. CONCLUSION: Disparities exist between the management and outcomes of rural and metropolitan populations experiencing ACS. While the causes of these discrepancies are multifactorial; the onus is on the healthcare system to effectively reduce associated morbidity and mortality. Improvements in the management of ACS may be achieved through a continued reduction in call-to-needles time via the use of remote and mobile thrombolysis services as well as improvements in in-hospital risk assessment in order to flag and investigate those at risk of ACS.

The evolving role of springs in craniofacial surgery: the first 100 clinical cases.

BACKGROUND: The use of springs in craniofacial surgery originated at Sahlgrenska University Hospital in 1997 as a way of remodeling the cranial vault postoperatively. METHODS: The hospital records of the first 100 operations involving spring placement were analyzed retrospectively. Demographic, perioperative, and postoperative data were recorded. RESULTS: Two hundred forty-six springs were used in 96 patients. Results for sagittal, metopic, bicoronal, multiple synostoses, and midface surgery are presented. In total, five patients (5 percent) required further surgery because of undercorrection. There were no major complications. Spring dislodgement (5 percent) was the most common complication in early cases. Raised intracranial pressure resulted in a protocol change with the use of compressive springs. The data compare favorably with those of standard craniofacial procedures performed in the same unit. CONCLUSIONS: This therapeutic modality in craniofacial surgery has allowed minimization of the extent of surgery without compromising clinical outcomes. Springs have now become part of the authors' treatment protocol for craniosynostosis and midface surgery. The authors have shown the use of these techniques to be safe and, in selected situations, to offer significant advantages over other methods of treatment.