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Fat metabolism is an important and complex biochemical reaction in vivo and is regulated by many factors. Recently, the findings on high expression of fibroblast growth factor-16 (FGF16) in brown adipose tissue have led to an interest in exploring its role in lipogenesis and lipid metabolism. The study cloned the goat’s FGF16 gene 624 bp long, including the complete open reading frame that encodes 207 amino acids. We found that FGF16 expression is highest in goat kidneys and hearts, followed by subcutaneous fat and triceps. Moreover, the expression of FGF16 reached its peak on the 2nd day of adipocyte differentiation (P < 0.01) and then decreased significantly. We used overexpression and interference to study the function of FGF16 gene in goat intramuscular preadipocytes. Silencing of FGF16 decreased adipocytes lipid droplet aggregation and triglyceride synthesis. This is in contrast to the situation where FGF16 is overexpressed. Furthermore, knockdown of FGF16 also caused down-regulated expression of genes associated with adipocyte differentiation including CCAAT enhancer-binding protein beta (P < 0.01), fatty acid-binding protein-2 (P < 0.01) and sterol regulatory element binding protein-1 (P < 0.05), but the preadipocyte factor-1 was up-regulated. At the same time, the genes adipose triglyceride lipase (P < 0.01) and hormone-sensitive lipase (P < 0.05) associated with triglyceride breakdown were highly expressed. Next, we locked the fibroblast growth factor receptor-4 (FGFR4) through the protein interaction network and interfering with FGF16 to significantly reduce FGFR4 expression. It was found that the expression profile of FGFR4 in adipocyte differentiation was highly similar to that of FGF16. Overexpression and interference methods confirmed that FGFR4 and FGF16 have the same promoting function in adipocyte differentiation. Finally, using co-transfection technology, pc-FGF16 and siRNA-FGFR4, siRNA2-FGF16 and siRNA-FGFR4 were combined to treat adipocytes separately. It was found that in the case of overexpression of FGF16, cell lipid secretion and triglyceride synthesis showed a trend of first increase and then decrease with increasing interference concentration. In the case of interference with FGF16, lipid secretion and triglyceride synthesis showed a downward trend with the increase of interference concentration. These findings illustrated that FGF16 mediates adipocyte differentiation via receptor FGFR4 expression and contributed to further study of the functional role of FGF16 in goat fat formation.
In this paper, the generation of relativistic electron mirrors (REM) and the reflection of an ultra-short laser off the mirrors are discussed, applying two-dimension particle-in-cell simulations. REMs with ultra-high acceleration and expanding velocity can be produced from a solid nanofoil illuminated normally by an ultra-intense femtosecond laser pulse with a sharp rising edge. Chirped attosecond pulse can be produced through the reflection of a counter-propagating probe laser off the accelerating REM. In the electron moving frame, the plasma frequency of the REM keeps decreasing due to its rapid expansion. The laser frequency, on the contrary, keeps increasing due to the acceleration of REM and the relativistic Doppler shift from the lab frame to the electron moving frame. Within an ultra-short time interval, the two frequencies will be equal in the electron moving frame, which leads to the resonance between laser and REM. The reflected radiation near this interval and corresponding spectra will be amplified due to the resonance. Through adjusting the arriving time of the probe laser, a certain part of the reflected field could be selectively amplified or depressed, leading to the selective adjustment of the corresponding spectra.
Ovarian follicle selection is a natural biological process in the pre-ovulatory hierarchy in birds that drives growing follicles to be selected within the ovulatory cycle. Follicle selection in birds is strictly regulated, involving signaling pathways mediated by dietary nutrients, gonadotrophic hormones and paracrine factors. This study aimed to test the hypothesis that dietary Ca may participate in regulating follicle selection in laying ducks through activating the signaling pathway of cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/extracellular signal-regulated kinase (ERK), possibly mediated by gonadotrophic hormones. Female ducks at 22 weeks of age were initially fed one of two Ca-deficient diets (containing 1.8% or 0.38% Ca) or a Ca-adequate control diet (containing 3.6% Ca) for 67 days (depletion period), then all birds were fed the Ca-adequate diet for an additional 67 days (repletion period). Compared with the Ca-adequate control, ducks fed 0.38% Ca during the depletion period had significantly decreased (P < 0.05) numbers of hierarchical follicles and total ovarian weight, which were accompanied by reduced egg production. Plasma concentration of FSH was decreased by the diet containing 1.8% Ca but not by that containing 0.38%. The ovarian content of cAMP was increased with the two Ca-deficient diets, and phosphorylation of PKA and ERK1/2 was increased with 0.38% dietary Ca. Transcripts of ovarian estradiol receptor 2 and luteinizing hormone receptor (LHR) were reduced in the ducks fed the two Ca-deficient diets (P < 0.05), while those of the ovarian follicle stimulating hormone receptor (FSHR) were decreased in the ducks fed 0.38% Ca. The transcript abundance of ovary gap junction proteins, A1 and A4, was reduced with the Ca-deficient diets (P < 0.05). The down-regulation of gene expression of gap junction proteins and hormone receptors, the increased cAMP content and the suppressed hierarchical follicle numbers were reversed by repletion of dietary Ca. These results indicate that dietary Ca deficiency negatively affects follicle selection of laying ducks, independent of FSH, but probably by activating cAMP/PKA/ERK1/2 signaling pathway.
Introduction: Emergency department (ED) flow is a strong predictor of patient safety, quality of care and provider satisfaction. Throughput interventions have been shown to improve flow metrics, yet few studies have considered MD leadership roles and evaluated provider experience. Our objective was to evaluate the emergency physician lead (EPL) role, a novel MD staffing initiative. Methods: This mixed-method observational time series analysis evaluated ED metrics at two tertiary EDs including ED length of stay (LOS), EMS Park LOS and physician initial assessment (PIA) time as well as 72-hour readmit and left without being seen (LWBS) rates. Data was collected from the ED information system database for control (Dec 6, 2017-Feb 28, 2018 SITE1 and Mar 1–May 31, 2018 SITE2), pre (Sept 3-Nov 30, 2018 SITE 1 and Dec 3, 2018-Feb 28, 2019 SITE2) and post (Dec 3, 2018 –Feb 28, 2019 SITE1, Mar 1- May 31, 2019 SITE2) periods for adult patients presenting to each site. Site data was analyzed independently using descriptive and inferential statistics to calculate differences in means, and means were compared using t-tests. A survey elicited provider feedback from ED physicians, nurses, and EMS professionals on the effect of the EPL on throughput, timeliness of admissions and discharges, provider workload, and the EPL as a resource to other professionals. Results: The number of ED visits at SITE1 were 13136 (Ctrl), 13236 (Pre) and 13137 (Post), and at SITE2 were 14371(Ctrl), 13866 (Pre) and 14962 (Post). Mean ED LOS was decreased by 17 min in post vs control and 20 min vs pre at SITE1 (p < 0.01). SITE2 saw an increase in ED LOS by 7 min vs control and 8 min vs pre (p < 0.01). EMS LOS at SITE1 was decreased by 21 min vs control and 22 min vs pre (p < 0.01), but was increased at SITE2 by 2 min vs control (p = 0.09) and 14 min vs pre (p < 0.01). PIA time at SITE1 was decreased by 15 min vs control (p < 0.01) and 13 min vs pre and increased by 5 min vs control and 12 min vs pre at SITE2 (p < 0.01). 72 hour readmit and LWBS rates were unchanged at both sites. Qualitative feedback from ED providers highlighted the early provision of treatments and investigations by the EPL, and many felt the EPL was an important resource. Conclusion: The inclusion of both quantitative and qualitative data in this study provided a robust analysis of the impact of the EPL role and demonstrated modest but important improvements. A site-dependent, carefully considered implementation of the EPL role may improve ED metrics and provider experiences.
Introduction: Calgary's introduction of rentable electronic scooters (e-scooters) in July of 2019 was met with wild popularity, representing the third most popular launch after Tel-Aviv and Paris. The present study aims to characterize the injury burden seen in all Calgary Emergency Departments (EDs) and Urgent Care Centres (UCCs) attributable to e-scooters since their 2019 introduction. Methods: We retrospectively reviewed all electronic medical records of patients presenting to Calgary EDs or UCCs with the term “scooter” in the triage note, where exclusion criteria are considered for non e-scooter injuries (e.g: non-motorized scooters). Trends in scooter injuries will be compared between April - October 2018 (control arm preceding e-scooter introduction) and April - October 2019. Injury incidence, types, patient demographics, and relative risk compared to bicycle-related injuries will be determined. Descriptive statistics will be calculated. Moreover, 33 ED visits were brought in by EMS and provide information about injury types and locations of injuries involving EMS transport. Results: Preliminary data reveals 540 scooter-related visits (3.10% admitted/transferred) between July 8th and September 30th 2019 (mean age of 28, 56.30% male). Conversely, the number of bicycle-related visits and motor vehicle related injuries were 1482 and 586 (9.90% and 9.70% admitted/transferred) respectively over the same time period suggesting a greater burden but likely a lower per-ride incidence of injury requiring ED or UCC care. Moreover, between July 8th to October 1st 2019, 33 e-scooter presentations involved EMS (21.21% admitted to hospital), where 12.12% involved upper extremity injury, 21.21% were lower extremity injuries, and 6.06% were head injuries (mean age of 34, 48.48% male). Conversely, estimated EMS transfers to EDs or UCCs for bicycle injuries and motor vehicle injuries were 197 and 463 respectively over the same time period. ICU admissions or fatality were not recorded. Conclusion: Representing the most comprehensive study of e-scooter injury patterns in Canada to date, we here demonstrate a significant injury burden attributable to e-scooters following their introduction in Calgary in 2019. Bicycle-related and motor vehicle injuries were both more prevalent in this time period, and required more EMS visits. Further characterization of injury types, injuries and comparison with injury patterns prior to e-scooter introduction is yet to be determined.
We investigate the phased evolution and variation of the South Asian monsoon and resulting weathering intensity and physical erosion in the Himalaya–Karakoram Mountains since late Pliocene time (c. 3.4 Ma) using a comprehensive approach. Neodymium and strontium isotopic compositions and single-grain zircon U–Pb age spectra reveal the sources of the deposits in the east Arabian Sea, and show a combination of sources from the Himalaya and the Karakoram–Kohistan–Ladakh Mountains, with sediments from the Indian Peninsula such as the Deccan Traps or Craton. We interpret shifts in the sediment sources to have been forced by sea-level changes that correlate with South Asian monsoon rainfall variation since late Pliocene time. We collected 908 samples from the International Ocean Discovery Program Hole U1456A, which was drilled in the east Arabian Sea. Time series of hematite content and grain size of the sediments were examined downcore. We found South Asian monsoon precipitation and weathering intensity experienced three phases from late Pliocene time. Lower monsoon precipitation, with a lower variability and strong weathering intensity, occurred during 3.4–2.4 Ma; an increased and more variable South Asian monsoon rainfall, along with strengthened but fluctuating weathering intensity, occurred at 1.8–1.1 Ma; and a reduced rainfall with lower South Asian monsoon precipitation variability and moderate weathering intensity marked the period 1.1–0.1 Ma. Maximum entropy spectral analysis and wavelet transform show that there were orbital-dominated cycles of periods c. 100 and c. 41 ka in these proxy-based time series. We propose that the monsoon, sea level, global temperature and insolation together forced the weathering and erosion in SW Asia.
Neuroticism is associated with the onset and maintenance of a number of mental health conditions, as well as a number of deleterious outcomes (e.g. physical health problems, higher divorce rates, lost productivity, and increased treatment seeking); thus, the consideration of whether this trait can be addressed in treatment is warranted. To date, outcome research has yielded mixed results regarding neuroticism's responsiveness to treatment, perhaps due to the fact that study interventions are typically designed to target disorder symptoms rather than neuroticism itself. The purpose of the current study was to explore whether a course of treatment with the unified protocol (UP), a transdiagnostic intervention that was explicitly developed to target neuroticism, results in greater reductions in neuroticism compared to gold-standard, symptom focused cognitive behavioral therapy (CBT) protocols and a waitlist (WL) control condition.
Patients with principal anxiety disorders (N = 223) were included in this study. They completed a validated self-report measure of neuroticism, as well as clinician-rated measures of psychological symptoms.
At week 16, participants in the UP condition exhibited significantly lower levels of neuroticism than participants in the symptom-focused CBT (t(218) = −2.17, p = 0.03, d = −0.32) and WL conditions(t(207) = −2.33, p = 0.02, d = −0.43), and these group differences remained after controlling for simultaneous fluctuations in depression and anxiety symptoms.
Treatment effects on neuroticism may be most robust when this trait is explicitly targeted.
Accretionary orogens contain key evidence for the conversion of oceanic to continental crust. The late tectonic history and closure time of the Palaeo-Asian Ocean are recorded in the Mazongshan subduction–accretion complex in the southern Beishan margin of the Central Asian Orogenic Belt. We present new data on the structure, petrology, geochemistry and zircon U–Pb isotope ages of the Mazongshan subduction–accretion complex, which is a tectonic mélange with a block-in-matrix structure. The blocks are of serpentinized peridotite, basalt, gabbro, basaltic andesite, chert and seamount sediments within a matrix that is mainly composed of fore-arc-trench turbidites. U–Pb zircon ages of two gabbros are 454.6 ± 2.5 Ma and 434.1 ± 3.6 Ma, an andesite has a U–Pb zircon age of 451.3 ± 3.5 Ma and a tuffaceous slate has the youngest U–Pb zircon age of 353.6 ± 5.1 Ma. These new isotopic ages, combined with published data on ophiolitic mélanges from central Beishan, indicate that the subduction–accretion of Beishan in the southernmost Central Asian Orogenic Belt lasted until Late Ordovician – Early Carboniferous time. Structure and age data demonstrate that the younging direction of accretion was southwards and that the subduction zone dipped continuously to the north. Accordingly, these results record the conversion of oceanic to continental crust in the southern Beishan accretionary collage.
The objective of this study was to evaluate the efficacy and safety of ziprasidone adjunctive to a mood stabilizer for the maintenance treatment of bipolar mania.
Male and female subjects with bipolar I disorder with MRS 3 14 were enrolled. Subjects achieving ≥ 8 consecutive weeks of stability with open-label ziprasidone (80-160 mg/d) and lithium or divalproex were randomized into the 6-month double-blind maintenance period, to ziprasidone + mood stabilizer or placebo + mood stabilizer. The primary and key secondary end points were the time to intervention for a mood episode, and time to discontinuation for any reason, respectively. Inferential analysis was performed using a Kaplan-Meier product-limit estimator (Log-rank test).
127 and 112 subjects were randomized to and treated in the ziprasidone and placebo groups, respectively. The time to intervention for a mood episode was significantly different, favoring ziprasidone (p = 0.0104). 19.7% and 32.4% of ziprasidone and placebo subjects, respectively, required intervention for a mood episode. Time to discontinuation for any reason was significantly different (p = 0.0047), favoring ziprasidone. Among treatment-emergent adverse events occurring in the double-blind period, the only event occurring more frequently in the ziprasidone group than in the placebo group (≥ 5%) was tremor (6.3% vs 3.6%, respectively).
These results demonstrate that ziprasidone is an effective, safe, and well-tolerated adjunctive treatment with a mood stabilizer for long-term maintenance treatment of bipolar mania.
Immigration stress appears to augment the risk for suicide behaviors for Latinos. Yet, specific risk factors that contribute to suicidal ideation (SI) among diverse Latino immigrant populations are not well established.
Data were collected in Boston, Madrid and Barcelona using a screening battery assessing mental health, substance abuse risk, trauma exposure, demographics, and sociocultural factors. Prevalence rates of lifetime and 30-day SI were compared across sites. Logistic regression modeling was used to identify sociodemographic, clinical, and sociocultural-contextual factors associated with 30-day SI.
Five hundred and sixty-seven Latino patients from primary care, behavioral health and HIV clinics and community agencies participated. Rates of lifetime SI ranged from 29–35%; rates for 30-day SI were 21–23%. Rates of SI were not statistically different between sites. Factors associated with SI included exposure to discrimination, lower ethnic identity, elevated family conflict, and low sense of belonging (P < 0.01). In the adjusted model, higher scores on depression, posttraumatic stress disorder, and trauma exposure were significantly associated with 30-day SI (OR = 1.14, 1.04, and 7.76, respectively). Greater number of years living in the host country was significantly associated with increased odds of having SI (OR = 2.22) while having citizenship status was associated with lower odds (OR = 0.45).
Latinos suffering depression, trauma exposure, and immigration stressors are more likely to experience SI. Despite differences in country of origin, education, and other demographic factors between countries, rates of SI did not differ. Recommendations for prevention and clinical practice for addressing suicidal ideation risk among Latino immigrants are discussed.
Although alienation toward parents is important for children (for current mental health status or later interpersonal relationships in adulthood), it is undervalued and even lacks a standardized tool of assessment. Moreover, the large number of left-behind children in China is a cause of public concern. However, their experienced alienation toward their parents remains unclear, which may be important for early detection or intervention for behavioral problems in this population. Hence, the current study aimed to develop an alienation inventory for children and then use it to investigate the experienced alienation toward parents in Chinese left-behind children.
Two studies were carried out. Study 1 was designed to develop a standard inventory of alienation toward parents (IAP). In study 2, 8361 children and adolescents (6704 of them were left-behind status) of the Chongqing area, aged between 8 and 19 years old, were recruited for investigation. All participants were surveyed with a standard sociodemographic questionnaire, children's cognitive style questionnaire, children's depression inventory, adolescent self-rating life events checklist, and newly built IAP in study 1.
In study 1, we developed a two-component (communication and emotional distance) and 18-item (9 items for maternal or paternal form, respectively) IAP questionnaire. In study 2, exploratory factor analysis indicated an expected two-factor structure of IAP, which was confirmed by confirmatory factor analysis. The Cronbach's alpha coefficients showed a good reliability (0.887 and 0.821 for maternal and paternal form, respectively). Children with absent mother experienced the highest alienation toward parents. Boys as well as children aged 8–10 years old experienced higher alienation toward parents. Poor communication with parents (sparse or no connection), level of left-behind condition (parents divorced, been far away from parents), and psychosocial vulnerability (stressful life events, negative cognitive style) were risk factors of alienation toward parents.
The current study develops a two-factor (communication and emotional distance) IAP, which offers a reliable tool to assess experienced alienation of affection toward parents in children aged between 8 and 19 years old. Our result is the first investigation of experienced alienation and potential influential factors in Chinese left-behind children. The findings that children with absent mother experience higher alienation toward parents, as well as three recognized risk factors for alienation of affection toward parents (poor communication with absent parents, worse left-behind condition, and psychosocial vulnerability), give valuable guidance for parents who intend to leave or who are already leaving as well as for government policymaking.
US Latinos have higher rates of substance use disorders (SUDs) than Latinas, but Latinas face substantial barriers to treatment and tend to enter care with higher SUD severity. Immigrant Latinas may face greater barriers to care than native-born despite lower overall SUD prevalence. This study aimed to identify how SUD treatment needs of Latinos are addressed depending on patient gender and immigrant status within an urban healthcare system serving a diverse population.
Data from electronic health records of adult Latino/a primary care patients (n = 29,887 person-years) were used to identify rates of SUD treatment in primary and specialty care. Treatment characteristics and receipt of adequate care were compared by gender and immigrant status.
Tobacco was the most frequently treated substance followed by alcohol and other drugs. Forty-six percent of SUD patients had a comorbid psychiatric condition. Treatment rates ranged from 2.52% (female non-immigrants) to 8.38% (male immigrants). Women had lower treatment rates than men, but male and female immigrants had significantly higher treatment rates than their non-immigrant counterparts. Receipt of minimally adequate outpatient care varied significantly by gender and immigrant status (female non-immigrants 12.5%, immigrants 28.57%; male non-immigrants 13.46%, immigrants 17.09%) in unadjusted and adjusted analyses.
Results indicate overall low prevalence of SUD treatment in the healthcare system. Low rates of minimally adequate care evidence the challenge of delivering integrated behavioral healthcare for Latinos with SUD. Results also demonstrate gender and immigrant status disparities in an unexpected direction, with immigrant women receiving the highest rates of adequate care.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Cognitive dysfunction is recognized as a core feature of schizophrenia and is considered an important predictor of functional outcomes. Despite this, current treatment strategies largely fail to ameliorate these cognitive impairments. In order to develop more efficient treatment strategies, a better understanding of the pathogenesis of cognitive dysfunction is needed. Accumulating evidence indicates that genetic risk of schizophrenia contributes to cognitive dysfunction. However, the precise genetic variants jointly influencing schizophrenia and cognitive function remain to be determined.
Here, we aimed to identify gene loci shared between schizophrenia and general cognitive function, a phenotype that captures the shared variation in performance across several cognitive domains.
Using a Bayesian statistical framework, we compared genome-wide association study (GWAS) data on schizophrenia from the Psychiatric Genomics Consortium cohort (n = 79,757) with GWAS data on general cognitive function from the CHARGE Consortium (n = 53,949). By conditioning the false discovery rate (FDR) on shared associations, this statistical approach increases power to detect gene loci.
We observed substantial polygenetic overlap between schizophrenia and general cognitive function, which replicated across independent schizophrenia sub-studies. Using the conditional FDR approach we increased discovery of gene loci and identified 13 loci shared between schizophrenia and general cognitive function. The majority of these loci (11/13) shows opposite directions of allelic effects in the phenotypes, in line with previous genetic studies and the observed cognitive dysfunction in schizophrenia.
Our study extends the current understanding of the genetic etiology influencing schizophrenia and general cognitive function by identifying shared gene loci between the phenotypes.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
We present the analysis of global sympagic primary production (PP) from 300 years of pre-industrial and historical simulations of the E3SMv1.1-BGC model. The model includes a novel, eight-element sea ice biogeochemical component, MPAS-Seaice zbgc, which is resolved in three spatial dimensions and uses a vertical transport scheme based on internal brine dynamics. Modeled ice algal chlorophyll-a concentrations and column-integrated values are broadly consistent with observations, though chl-a profile fractions indicate that upper ice communities of the Southern Ocean are underestimated. Simulations of polar integrated sea ice PP support the lower bound in published estimates for both polar regions with mean Arctic values of 7.5 and 15.5 TgC/a in the Southern Ocean. However, comparisons of the polar climate state with observations, using a maximal bound for ice algal growth rates, suggest that the Arctic lower bound is a significant underestimation driven by biases in ocean surface nitrate, and that correction of these biases supports as much as 60.7 TgC/a of net Arctic PP. Simulated Southern Ocean sympagic PP is predominantly light-limited, and regional patterns, particularly in the coastal high production band, are found to be negatively correlated with snow thickness.
Meat and milk from ruminants provide an important source of protein and other nutrients for human consumption. Although ruminants have a unique advantage of being able to consume forages and graze lands not suitable for arable cropping, 2% to 12% of the gross energy consumed is converted to enteric CH4 during ruminal digestion, which contributes approximately 6% of global anthropogenic greenhouse gas emissions. Thus, ruminant producers need to find cost-effective ways to reduce emissions while meeting consumer demand for food. This paper provides a critical review of the substantial amount of ruminant CH4-related research published in past decades, highlighting hydrogen flow in the rumen, the microbiome associated with methanogenesis, current and future prospects for CH4 mitigation and insights into future challenges for science, governments, farmers and associated industries. Methane emission intensity, measured as emissions per unit of meat and milk, has continuously declined over the past decades due to improvements in production efficiency and animal performance, and this trend is expected to continue. However, continued decline in emission intensity will likely be insufficient to offset the rising emissions from increasing demand for animal protein. Thus, decreases in both emission intensity (g CH4/animal product) and absolute emissions (g CH4/day) are needed if the ruminant industries continue to grow. Providing producers with cost-effective options for decreasing CH4 emissions is therefore imperative, yet few cost-effective approaches are currently available. Future abatement may be achieved through animal genetics, vaccine development, early life programming, diet formulation, use of alternative hydrogen sinks, chemical inhibitors and fermentation modifiers. Individually, these strategies are expected to have moderate effects (<20% decrease), with the exception of the experimental inhibitor 3-nitrooxypropanol for which decreases in CH4 have consistently been greater (20% to 40% decrease). Therefore, it will be necessary to combine strategies to attain the sizable reduction in CH4 needed, but further research is required to determine whether combining anti-methanogenic strategies will have consistent additive effects. It is also not clear whether a decrease in CH4 production leads to consistent improved animal performance, information that will be necessary for adoption by producers. Major constraints for decreasing global enteric CH4 emissions from ruminants are continued expansion of the industry, the cost of mitigation, the difficulty of applying mitigation strategies to grazing ruminants, the inconsistent effects on animal performance and the paucity of information on animal health, reproduction, product quality, cost-benefit, safety and consumer acceptance.
The Square Kilometre Array (SKA) is a planned large radio interferometer designed to operate over a wide range of frequencies, and with an order of magnitude greater sensitivity and survey speed than any current radio telescope. The SKA will address many important topics in astronomy, ranging from planet formation to distant galaxies. However, in this work, we consider the perspective of the SKA as a facility for studying physics. We review four areas in which the SKA is expected to make major contributions to our understanding of fundamental physics: cosmic dawn and reionisation; gravity and gravitational radiation; cosmology and dark energy; and dark matter and astroparticle physics. These discussions demonstrate that the SKA will be a spectacular physics machine, which will provide many new breakthroughs and novel insights on matter, energy, and spacetime.
Nutritional therapy is a cornerstone of burns management. The optimal macronutrient intake for wound healing after burn injury has not been identified, although high-energy, high-protein diets are favoured. The present study aimed to identify the optimal macronutrient intake for burn wound healing. The geometric framework (GF) was used to analyse wound healing after a 10 % total body surface area contact burn in mice ad libitum fed one of the eleven high-energy diets, varying in macronutrient composition with protein (P5−60 %), carbohydrate (C20−75 %) and fat (F20−75 %). In the GF study, the optimal ratio for wound healing was identified as a moderate-protein, high-carbohydrate diet with a protein:carbohydrate:fat (P:C:F) ratio of 1:4:2. High carbohydrate intake was associated with lower mortality, improved body weight and a beneficial pattern of body fat reserves. Protein intake was essential to prevent weight loss and mortality, but a protein intake target of about 7 kJ/d (about 15 % of energy intake) was identified, above which no further benefit was gained. High protein intake was associated with delayed wound healing and increased liver and spleen weight. As the GF study demonstrated that an initial very high protein intake prevented mortality, a very high-protein, moderate-carbohydrate diet (P40:C42:F18) was specifically designed. The dynamic diet study was also designed to combine and validate the benefits of an initial very high protein intake for mortality, and subsequent moderate protein, high carbohydrate intake for optimal wound healing. The dynamic feeding experiment showed switching from an initial very high-protein diet to the optimal moderate-protein, high-carbohydrate diet accelerated wound healing whilst preventing mortality and liver enlargement.