Picoflare jets power the solar wind emerging from a coronal hole on the Sun.

Coronal holes are areas on the Sun with open magnetic field lines. They are a source region of the solar wind, but how the wind emerges from coronal holes is not known. We observed a coronal hole using the Extreme Ultraviolet Imager on the Solar Orbiter spacecraft. We identified jets on scales of a few hundred kilometers, which last 20 to 100 seconds and reach speeds of ~100 kilometers per second. The jets are powered by magnetic reconnection and have kinetic energy in the picoflare range. They are intermittent but widespread within the observed coronal hole. We suggest that such picoflare jets could produce enough high-temperature plasma to sustain the solar wind and that the wind emerges from coronal holes as a highly intermittent outflow at small scales.

Ultra-high-resolution observations of persistent null-point reconnection in the solar corona.

Magnetic reconnection is a key mechanism involved in solar eruptions and is also a prime possibility to heat the low corona to millions of degrees. Here, we present ultra-high-resolution extreme ultraviolet observations of persistent null-point reconnection in the corona at a scale of about 390 km over one hour observations of the Extreme-Ultraviolet Imager on board Solar Orbiter spacecraft. The observations show formation of a null-point configuration above a minor positive polarity embedded within a region of dominant negative polarity near a sunspot. The gentle phase of the persistent null-point reconnection is evidenced by sustained point-like high-temperature plasma (about 10 MK) near the null-point and constant outflow blobs not only along the outer spine but also along the fan surface. The blobs appear at a higher frequency than previously observed with an average velocity of about 80 km s-1 and life-times of about 40 s. The null-point reconnection also occurs explosively but only for 4 minutes, its coupling with a mini-filament eruption generates a spiral jet. These results suggest that magnetic reconnection, at previously unresolved scales, proceeds continually in a gentle and/or explosive way to persistently transfer mass and energy to the overlying corona.

ß-Delayed One and Two Neutron Emission Probabilities Southeast of

The ß-delayed one- and two-neutron emission probabilities (P_{1n} and P_{2n}) of 20 neutron-rich nuclei with N≥82 have been measured at the RIBF facility of the RIKEN Nishina Center. P_{1n} of ^{130,131}Ag, ^{133,134}Cd, ^{135,136}In, and ^{138,139}Sn were determined for the first time, and stringent upper limits were placed on P_{2n} for nearly all cases. ß-delayed two-neutron emission (ß2n) was unambiguously identified in ^{133}Cd and ^{135,136}In, and their P_{2n} were measured. Weak ß2n was also detected from ^{137,138}Sn. Our results highlight the effect of the N=82 and Z=50 shell closures on ß-delayed neutron emission probability and provide stringent benchmarks for newly developed macroscopic-microscopic and self-consistent global models with the inclusion of a statistical treatment of neutron and γ emission. The impact of our measurements on r-process nucleosynthesis was studied in a neutron star merger scenario. Our P_{1n} and P_{2n} have a direct impact on the odd-even staggering of the final abundance, improving the agreement between calculated and observed Solar System abundances. The odd isotope fraction of Ba in r-process-enhanced (r-II) stars is also better reproduced using our new data.

Aggressive paediatric camptodactyly: The evolution of a proposed treatment algorithm.

INTRODUCTION: It is a long-established teaching to avoid operating on camptodactyly unless there is a failure of non-operative treatment, such as serial splinting and hand therapy, and there is an established proximal interphalangeal joint (PIPJ) contracture of 60°; a recent systematic review reflects this continuing approach, with some papers advocating intervention with a lesser degree of contracture. AIM: To evaluate whether early flexor digitorum superficialis (FDS) release, followed by gentle passive manipulation (GPM), will correct severe 'congenital' camptodactyly, if undertaken at an earlier age than usual, thus avoiding the more aggressive surgical approach required in the established adolescent cases. METHOD: The surgical technique and treatment algorithm are described. A multi-centre case series is presented; data analysis included patient demographics, syndromic association, side/digit affected, ages at onset, progression, referral and at surgery, operation details, pre- and post-operative contracture and range of motion. RESULTS: There were 12 patients (3 males, 9 females) who underwent 15 operations for 24 involved digits. Patients had surgery by 3 months (median) post-referral, and there was a significant improvement in median (range) PIPJ contracture (90°(30°-90°) vs. 0°(0°-45°); p<0.001) and range of motion (0°(0°-60°) vs. 90°(50°-95°); p<0.001), at a median post-operative follow-up of 2.5 years. According to the Siegert grade, 87.5% of digits had excellent/good post-operative outcomes and 12.5% had fair outcomes. CONCLUSION: This paper specifically addresses the problem of aggressive and progressive camptodactyly in the young child. By this, we mean patients who have failed non-operative treatment and have PIPJ contractures ≥60°, and those whose contractures have increased by 30° within 1 year. All cases responded to early FDS release and GPM, hence correcting the PIPJ contracture. However, cases with multiple digital involvement, whether syndromic or not, and failed previous surgery or the older child, required additional procedures to restore a dynamic dorsal apparatus and active extension.

Uptake and acceptability of medical male circumcision among young males in two culturally distinct settings in South Africa: A longitudinal, community-based study (the MACHO study).

BACKGROUND: Young South Africans experience high rates of HIV infection. While nationally scaled medical male circumcision (MMC) can help to curb HIV infection rates in countries such as South Africa (SA), MMC uptake has not been consistent or universal, suggesting variable acceptability among men. Both MMC and traditional male circumcision (TMC) are practised in SA. For male circumcision to be most effective for HIV prevention, it should be performed prior to sexual debut with complete removal of the foreskin. OBJECTIVES: The MACHO (Male Adolescent Choices for HIV Prevention Options) study investigated uptake of and preference for MMC v. TMC in two culturally distinct settings in SA. METHODS: This observational, longitudinal, cohort study investigated circumcision preferences and uptake in 100 males (aged 14 - 17 years) and their legal guardians in Cape Town (Western Cape Province) and Soweto (Gauteng Province). Data were collected via surveys administered every 4 months over a 24-month period. RESULTS: A total of 100 uncircumcised adolescent boys (Cape Town n=50, Soweto n=50; mean (interquartile range) age 15 (14 - 16) years) and their guardians were enrolled. At baseline, 42 boys from Soweto (84%) and none from Cape Town expressed a preference for MMC over TMC. Sowetan participants were more likely to elect circumcision (MMC n=11 (22%), TMC n=1 (2%)) than those from Cape Town (TMC n=1 (2%), MMC n=0) over 13.6 months of follow-up (hazard ratio 18.9; 95% confidence interval 2.37 - 150.71; p=0.006). CONCLUSIONS: MMC was the preferred option for young men in Soweto compared with those in Cape Town, and this translated into practice. Despite knowledge of the benefits of early MMC, many participants delayed uptake, potentially reducing the MMC benefits before sexual debut. Programmes promoting circumcision should consider the influence of local practices. To realise full HIV prevention benefits, efforts should be made to ensure that circumcision is promoted, and that all circumcision is safe, performed prior to sexual debut, and contextually responsive.

Reducing 30-day post gastrostomy insertion mortality with a feeding issues multidisciplinary team meeting.

INTRODUCTION: Decision-making regarding percutaneous endoscopic gastrostomy (PEG) insertion can be complex both medically and ethically. Thirty-day mortality following (PEG) insertion is an important quality indicator for endoscopy accreditation and for service evaluation. It also forms part of the measures assessed within the 'Getting It Right First Time' programme (GIRFT). We aimed to assess the impact of a newly adopted Feeding Issues MDT (FIMDT) and the clinical application of the Royal Free Gastrostomy Score (RFGS). METHOD: We adopted a retrospective observational methodology to assess the impact of a feeding issues MDT within our trust. The included study period ran from January 2016 to December 2019 (4 years). This formed part of a quality improvement (QI) project initiated upon receipt of the GIRFT report for our NHS trust. Statistical analysis and QI methodology was used to interpret and present the data. RESULTS: Two hundred and sixty eight PEG insertions occurred during the study period. 188 PEGs were inserted prior to the start of FIMDT and 45 following its inception. On average there were 66 PEGs performed per year. There was no significant difference in age for those undergoing PEG insertion pre (68 years) and post (69 years) FIMDT adoption. Prior to FIMDT those that died within 30 days post PEG were significantly older than those who did not (p < 0.001), whilst following FIMDT adoption there was no such difference. Prior to FIMDT the 30-day post PEG mortality was 10.64%, whilst following adoption of the FIMDT the mortality rate fell to 6.6% (p = 0.04). The mean number of procedures performed between a 30-day mortality occurring rose from 7.5 to 13.6. Furthermore, the mean number of days between a 30-day post insertion mortality occurring also rose from a mean of 53.0-111.8, pre and post FIMDT adoption. The Royal Free Gastrostomy Score (RFGS) for those discussed at FIMDT and declined for PEG insertion was significantly higher than those accepted for PEG insertion (p = 0.01). Over the entire study period those who died within 30 days following PEG insertion had a significantly greater RFGS (p < 0.0001). CONCLUSION: In our trust the adoption of a FIMDT has significantly reduced the 30-day mortality for PEG insertion. We have also demonstrated the clinical utility to assess mortality risk of the RFGS when making decisions around patient suitability for PEG insertion.

Postoperative cognitive dysfunction and mortality following lung transplantation.

Preliminary evidence suggests that postoperative cognitive dysfunction (POCD) is common after lung transplantation. The impact of POCD on clinical outcomes has yet to be studied. The association between POCD and longer-term survival was therefore examined in a pilot study of posttransplantation survivors. Forty-nine participants from a prior randomized clinical trial underwent a neurocognitive assessment battery pretransplantation and 6 months posttransplantation, including assessments of the domains of Executive Function (Trail Making Test, Stroop, Digit Span), Processing Speed (Ruff 2 and 7 Test, Digit Symbol Substitution Test), and Verbal Memory (Verbal Paired Associates, Logical Memory, Animal Naming, and Controlled Oral Word Association Test). During a 13-year follow-up, 33 (67%) participants died. Greater neurocognition was associated with longer survival (hazard ratio [HR] = 0.49 [0.25-0.96], P = .039), and this association was strongest on tests assessing Processing Speed (HR = 0.58 [0.36-0.95], P = .03) and Executive Function (HR = 0.52 [0.28-0.97], P = .040). In addition, unadjusted analyses suggested an association between greater Memory performance and lower risk of CLAD (HR = 0.54 [0.29-1.00], P = .050). Declines in Executive Function tended to be predictive of worse survival. These preliminary findings suggest that postoperative neurocognition is predictive of subsequent mortality among lung transplant recipients. Further research is needed to confirm these findings in a larger sample and to examine mechanisms responsible for this relationship.

Pediatric functional neurologic symptoms.

Functional neurologic disorders (FND) of children have many similarities to those of adults, and there is a potential to learn much from the study of FND in children. In this chapter we discuss multiple aspects of pediatric FND. These include their frequency, historic features, the diagnosis, and controversies over the nature of FND and the "correct" name that should be used. We also discuss methods of informing the child and family of the diagnosis, treatment, and prognosis. FND of children typically affect girls in the 10-14-years age range. The presentation is often polysymptomatic, with pain and lethargy accompanying loss of motor function. A common situation is a perfectionistic child who has taken on too much in her academic, sporting, cultural, and social life. Some children respond readily to treatment, but others have a prolonged illness.

Dynamically controlled deposition of colloidal nanoparticle suspension in evaporating drops using laser radiation.

Dynamic control of the distribution of polystyrene suspended nanoparticles in evaporating droplets is investigated using a 2.9 µm high power laser. Under laser radiation a droplet is locally heated and fluid flows are induced that overcome the capillary flow, and thus a reversal of the coffee-stain effect is observed. Suspension particles are accumulated in a localised area, one order of magnitude smaller than the original droplet size. By scanning the laser beam over the droplet, particles can be deposited in an arbitrary pattern. This finding raises the possibility for direct laser writing of suspended particles through a liquid layer. Furthermore, a highly uniform coating is possible by manipulating the laser beam diameter and exposure time. The effect is expected to be universally applicable to aqueous solutions independent of solutes (either particles or molecules) and deposited substrates.

Dietary Factors and Cognitive Decline.

Cognitive decline is an increasingly important public health problem, with more than 100 million adults worldwide projected to develop dementia by 2050. Accordingly, there has been an increased interest in preventive strategies that diminish this risk. It has been recognized that lifestyle factors including dietary patterns, may be important in the prevention of cognitive decline and dementia in later life. Several dietary components have been examined, including antioxidants, fatty acids, and B vitamins. In addition, whole dietary eating plans, including the Mediterranean diet (MeDi), and the Dietary Approaches to Stop Hypertension (DASH) diet, with and without weight loss, have become areas of increasing interest. Although prospective epidemiological studies have observed that antioxidants, fatty acids, and B vitamins are associated with better cognitive functioning, randomized clinical trials have generally failed to confirm the value of any specific dietary component in improving neurocognition. Several randomized trials have examined the impact of changing 'whole' diets on cognitive outcomes. The MeDi and DASH diets offer promising preliminary results, but data are limited and more research in this area is needed.

C60 fullerene localization and membrane interactions in RAW 264.7 immortalized mouse macrophages.

There continues to be a significant increase in the number and complexity of hydrophobic nanomaterials that are engineered for a variety of commercial purposes making human exposure a significant health concern. This study uses a combination of biophysical, biochemical and computational methods to probe potential mechanisms for uptake of C60 nanoparticles into various compartments of living immune cells. Cultures of RAW 264.7 immortalized murine macrophage were used as a canonical model of immune-competent cells that are likely to provide the first line of defense following inhalation. Modes of entry studied were endocytosis/pinocytosis and passive permeation of cellular membranes. The evidence suggests marginal uptake of C60 clusters is achieved through endocytosis/pinocytosis, and that passive diffusion into membranes provides a significant source of biologically-available nanomaterial. Computational modeling of both a single molecule and a small cluster of fullerenes predicts that low concentrations of fullerenes enter the membrane individually and produce limited perturbation; however, at higher concentrations the clusters in the membrane causes deformation of the membrane. These findings are bolstered by nuclear magnetic resonance (NMR) of model membranes that reveal deformation of the cell membrane upon exposure to high concentrations of fullerenes. The atomistic and NMR models fail to explain escape of the particle out of biological membranes, but are limited to idealized systems that do not completely recapitulate the complexity of cell membranes. The surprising contribution of passive modes of cellular entry provides new avenues for toxicological research that go beyond the pharmacological inhibition of bulk transport systems such as pinocytosis.

The interaction between artemether-lumefantrine and lopinavir/ritonavir-based antiretroviral therapy in HIV-1 infected patients.

BACKGROUND: Artemether-lumefantrine is currently the most widely recommended treatment of uncomplicated malaria. Lopinavir-based antiretroviral therapy is the commonly recommended second-line HIV treatment. Artemether and lumefantrine are metabolised by cytochrome P450 isoenzyme CYP3A4, which lopinavir/ritonavir inhibits, potentially causing clinically important drug-drug interactions. METHODS: An adaptive, parallel-design safety and pharmacokinetic study was conducted in HIV-infected (malaria-negative) patients: antiretroviral-naïve and those stable on lopinavir/ritonavir-based antiretrovirals. Both groups received the recommended six-dose artemether-lumefantrine treatment. The primary outcome was day-7 lumefantrine concentrations, as these correlate with antimalarial efficacy. Adverse events were solicited throughout the study, recording the onset, duration, severity, and relationship to artemether-lumefantrine. RESULTS: We enrolled 34 patients. Median day-7 lumefantrine concentrations were almost 10-fold higher in the lopinavir than the antiretroviral-naïve group [3170 versus 336 ng/mL; p = 0.0001], with AUC(0-inf) and Cmax increased five-fold [2478 versus 445 µg.h/mL; p = 0.0001], and three-fold [28.2 versus 8.8 µg/mL; p < 0.0001], respectively. Lumefantrine Cmax, and AUC(0-inf) increased significantly with mg/kg dose in the lopinavir, but not the antiretroviral-naïve group. While artemether exposure was similar between groups, Cmax and AUC(0-8h) of its active metabolite dihydroartemisinin were initially two-fold higher in the lopinavir group [p = 0.004 and p = 0.0013, respectively]. However, this difference was no longer apparent after the last artemether-lumefantrine dose. Within 21 days of starting artemether-lumefantrine there were similar numbers of treatment emergent adverse events (42 vs. 35) and adverse reactions (12 vs. 15, p = 0.21) in the lopinavir and antiretroviral-naïve groups, respectively. There were no serious adverse events and no difference in electrocardiographic QTcF- and PR-intervals, at the predicted lumefantrine Tmax. CONCLUSION: Despite substantially higher lumefantrine exposure, intensive monitoring in our relatively small study raised no safety concerns in HIV-infected patients stable on lopinavir-based antiretroviral therapy given the recommended artemether-lumefantrine dosage. Increased day-7 lumefantrine concentrations have been shown previously to reduce the risk of malaria treatment failure, but further evidence in adult patients co-infected with malaria and HIV is needed to assess the artemether-lumefantrine risk : benefit profile in this vulnerable population fully. Our antiretroviral-naïve patients confirmed previous findings that lumefantrine absorption is almost saturated at currently recommended doses, but this dose-limited absorption was overcome in the lopinavir group. TRIAL REGISTRATION: Clinical Trial Registration number NCT00869700. Registered on clinicaltrials.gov 25 March 2009.

Psychosocial Predictors of Mortality Following Lung Transplantation.

Lung transplantation has become an increasingly common treatment for patients with end-stage lung disease. Few studies have examined psychosocial risk factors for mortality in transplant recipients, despite evidence suggesting that elevated levels of negative affect are associated with greater mortality following major cardiac surgery. We therefore examined the relationship between negative affect early after lung transplantation and long-term survival in a sample of 132 lung transplant recipients (28 cystic fibrosis, 64 chronic obstructive pulmonary disease, 26 idiopathic pulmonary fibrosis, 14 other) followed for up to 13.5 years (median 7.4 years) following transplantation. Patients underwent both medical and psychosocial assessments 6 months following transplantation, which included the Beck Depression Inventory-II (BDI-II), Spielberger Anxiety Inventory, and General Health Questionnaire (GHQ). Over the course of follow-up, 80 (61%) participants died. Controlling for demographic factors, native lung disease, disease severity, family income, education level, social support, and frequency of posttransplant rejection, elevated symptoms of depression (BDI-II: HR = 1.31, p = 0.011) and distress (GHQ: HR = 1.28, p = 0.003) were associated with increased mortality. Higher levels of depression and general distress, but not anxiety, measured 6 months following lung transplantation are associated with increased mortality, independent of background characteristics and medical predictors.

Probing the epigenetic regulation of HIF-1α transcription in developing tissue.

HIF-1 is the master regulator of cellular hypoxia response; the oxygen sensitive HIF-1α subunit transactivates its own expression in hypoxia via a hypoxia response element (HRE) in the promoter of the HIF-1α gene. This transactivation loop significantly contributes to the build up of HIF-1α at the onset of hypoxia, with the binding of HIF-1 to the HIF-1α promoter being dependent on the epigenetic status of a CpG dinucleotide in the upstream HRE. Given the central role played by HIF-1 in tissue development, we sought to probe the epigenetic status of the HIF-1α HRE and that of its downstream target EPO in embryonic tissue. Our data shows that the CpG dinucleotide in HIF-1α HRE is unmethylated in several embryonic tissue samples, suggesting that transactivation of HIF-1α plays a significant role in HIF-1 mediated hypoxia response during development.

A novel framework for discharge uncertainty quantification applied to 500 UK gauging stations.

A generalized framework for discharge uncertainty estimation is presentedAllows estimation of place-specific discharge uncertainties for many catchmentsLocal conditions dominate in determining discharge uncertainty magnitudes.

Delirium affects length of hospital stay after lung transplantation.

BACKGROUND: Delirium is relatively common after lung transplantation, although its prevalence and prognostic significance have not been systematically studied. The purpose of the present study was to examine pretransplant predictors of delirium and the short-term impact of delirium on clinical outcomes among lung transplant recipients. METHODS: Participants underwent pretransplant cognitive testing using the Repeatable Battery for the Assessment of Neuropsychological Status and the Trail Making Test. After transplant, delirium was assessed using the Confusion Assessment Method until discharge. RESULTS: Sixty-three patients were transplanted between March and November 2013, of which 23 (37%) developed delirium. Among transplanted patients, 48 patients completed pretransplant cognitive testing. Better pretransplant cognitive function was associated with lower risk of delirium (odds ratio, 0.69 [95% confidence interval 0.48, 0.99], P = .043); and demographic and clinical features including native disease (P = .236), the Charlson comorbidity index (P = .581), and the lung allocation score (P = .871) were unrelated to risk of delirium, although there was a trend for women to experience delirium less frequently (P = .071). The presence (P = .006) and duration (P = .027) of delirium were both associated with longer hospital stays. CONCLUSION: Delirium occurs in more than one-third of patients after lung transplantation. Delirium was associated with poorer pretransplant cognitive functioning and longer hospital stays, after accounting for other medical and demographic factors.

Synthesis, characterization, and antiplasmodial activity of polymer-incorporated aminoquinolines.

In this research, aminoquinoline compounds were synthesized, characterized, and incorporated into water-soluble polymers to form conjugates. The conjugates were characterized by X-ray diffraction, thermal gravimetric analysis, scanning electron microscope, Fourier transform infrared spectroscopy, and nuclear magnetic resonance spectroscopy to confirm the successful incorporation of the aminoquinoline compound on to the polymer. The synthesized conjugates were screened for in vitro antiplasmodial activity in triplet test against chloroquine-sensitive strain of Plasmodium falciparum and chloroquine drug was used as a reference drug in all the experiments. A full dose-response was performed to determine the concentration inhibiting 50% of parasite growth (IC50 value). Polymeric conjugates containing 3-diethylamino-1-propylamine solubilizing units were found to be most active against the chloroquine-sensitive strain of P. falciparum.