Inflation of 430-parsec bipolar radio bubbles in the Galactic Centre by an energetic event.

The Galactic Centre contains a supermassive black hole with a mass of four million Suns1 within an environment that differs markedly from that of the Galactic disk. Although the black hole is essentially quiescent in the broader context of active galactic nuclei, X-ray observations have provided evidence for energetic outbursts from its surroundings2. Also, although the levels of star formation in the Galactic Centre have been approximately constant over the past few hundred million years, there is evidence of increased short-duration bursts3, strongly influenced by the interaction of the black hole with the enhanced gas density present within the ring-like central molecular zone4 at Galactic longitude |l| < 0.7 degrees and latitude |b| < 0.2 degrees. The inner 200-parsec region is characterized by large amounts of warm molecular gas5, a high cosmic-ray ionization rate6, unusual gas chemistry, enhanced synchrotron emission7,8, and a multitude of radio-emitting magnetized filaments9, the origin of which has not been established. Here we report radio imaging that reveals a bipolar bubble structure, with an overall span of 1 degree by 3 degrees (140 parsecs × 430 parsecs), extending above and below the Galactic plane and apparently associated with the Galactic Centre. The structure is edge-brightened and bounded, with symmetry implying creation by an energetic event in the Galactic Centre. We estimate the age of the bubbles to be a few million years, with a total energy of 7 × 1052 ergs. We postulate that the progenitor event was a major contributor to the increased cosmic-ray density in the Galactic Centre, and is in turn the principal source of the relativistic particles required to power the synchrotron emission of the radio filaments within and in the vicinity of the bubble cavities.

Infliximab serum concentrations and disease activity in perianal fistulizing Crohn's disease: a cross-sectional study.

INTRODUCTION: Several studies associate the presence of higher serum concentrations of infliximab (IFX) with fistula healing in perianal Crohn's disease (CD). This study aimed to evaluate serum IFX concentrations in patients with perianal fistulizing CD (PFCD) in the presence or absence of general, clinical, and radiological activities. METHODS: This was a cross-sectional study in patients with PFCD during maintenance treatment with IFX from two centers. Serum IFX concentrations were measured before their next infusion and anal fistulas were evaluated by clinical examination and magnetic resonance imaging (MRI), whenever possible, performed 90 days before or after serum collection. According to clinical scores, radiological activity, and disease markers, patients were classified as in remission or active disease. Mean serum IFX concentrations were compared between the groups. RESULTS: Thirty-eight patients with PFCD were included. Demographic characteristics were similar in patients with remission or active disease. The overall mean serum IFX concentration of the entire sample (n = 38) was 5.21 ± 4.75 µg/mL (median 3.63; IQR 1.44-8.82). Serum IFX levels were 6.25 ± 5.34 µg/mL (median 3.62; IQR 1.95-11.03) in the 23 (60.5%) patients in remission and 3.63 ± 3.24 µg/mL (median 3.63; IQR 1.32-6.43; p = 0.226) in the 15 (39 .5%) who presented active disease. When evaluating general, clinical, and radiological activity of PFCD, and deep remission in isolation, no statistical difference between the groups was observed (p = 0.226, p = 0.418, p = 0.126, and p = 0.232, respectively). The 13 (34.2%) patients with an optimized dose of IFX had significantly higher serum concentrations than the remaining 25 (65.8%) with a standard dose: 8.33 ± 4.41 µg/mL (median 8.36; IQR 3.82-11.20) vs. 3.59 ± 4.13 µg/mL (median 1.97; IQR 1.18-3.85) -p = 0.002. Patients in remission and with an optimized IFX dose had significantly higher serum IFX concentrations than those with a standard dose (p = 0.006), whereas no significant difference was observed among those with active disease (p = 0.083). CONCLUSION: There were no differences in IFX serum concentrations in patients with clinical or radiological active PFCD as compared with those in remission. Patients with an optimized IFX dose had significantly higher serum concentrations than those with a standard dose. Patients in remission and with an optimized IFX dose had significantly higher serum concentrations than those with a standard dose.

Ileal pouch-anal anastomosis with fluorescence angiography: a case-matched study.

AIM: An anastomotic leak in ileoanal pouch surgery may lead to pouch failure. Constructing a tension-free ileal pouch-anal anastomosis (IPAA) reduces this risk but can be technically challenging, balancing pouch vascularization with ileal mesenteric length and site of vessel ligation. Fluorescence angiography (FA) may help the clinician make a more balanced judgement. METHODS: Thirty-two patients undergoing minimally invasive completion proctectomy with FA-guided IPAA at two academic centres were matched and compared on a 1:1 basis to a historical group undergoing the same procedure without the use of this technique. RESULTS: Ligation of the ileocolic vessels was safely performed in 15/32 (47%) of FA patients compared with 5/32 (16%) of historical controls. One patient underwent intra-operative IPAA reconstruction after FA detected ischaemia. No anastomotic leak occurred with FA but there was only one in the historical controls (P = 0.31). The postoperative complication rate was similar between the two groups (P = 0.60). CONCLUSION: FA is applicable to IPAA surgery and may help to reduce perfusion-related anastomotic leaks. A prospective randomized trial is warranted.

Reduction in surgical stoma rates in Crohn's disease: a population-based time trend analysis.

AIM: Trends in surgical rates for Crohn's disease (CD) in the biological era are controversial. We aim to assess modern trends in the formation rates of surgical stomas. METHOD: Population-based surveillance in the Calgary Health Zone (CHZ), Canada, was conducted between 1 April 2002 and 31 March 2011, using the Discharge Abstract Database to identify adult patients with CD admitted to hospital and treated with surgical stoma formation (n = 545). Annual stoma incidence was calculated by dividing the number of incident stomas by the prevalence of CD in the CHZ. Time trend analysis of the stoma-formation rate was performed, expressed as annual percentage change (APC) with 95% CI. Stoma-formation rates were stratified according to procedure (emergency vs elective) and duration of stoma [temporary (reversed within 2 years of formation) vs permanent]. RESULTS: The overall rate of stoma formation between 2002 and 2011 showed a downwards trend, of a mean of 5.2% (95% CI: -8.5 to -1.8) per year, from a rate of 2.30 stomas/100 person-years (PY) in 2002 to 1.51 stomas/100 PY in 2011. The rate of emergency stoma formation decreased significantly from 2002 to 2011 (mean APC = -9.4%; 95% CI: -15.6 to -2.8), while the rate of elective ostomies essentially showed no change (mean APC = -0.9%; 95% CI: -5.3 to 3.8). The rate of temporary stoma formation decreased significantly, by 4.6% (95% CI: -7.3 to -1.8) per year, while permanent stoma formation was stable (APC = 1.0%; 95% CI: -4.0 to +6.3). CONCLUSION: A reduction in the overall rate of stoma formation in CD has been driven by fewer emergency stomas, although rates of permanent stoma have remained stable.

Multiple processes drive genetic structure of humpback whale (Megaptera novaeangliae) populations across spatial scales.

Elucidating patterns of population structure for species with complex life histories, and disentangling the processes driving such patterns, remains a significant analytical challenge. Humpback whale (Megaptera novaeangliae) populations display complex genetic structures that have not been fully resolved at all spatial scales. We generated a data set of nuclear markers for 3575 samples spanning the seven breeding stocks and substocks found in the South Atlantic and western and northern Indian Oceans. For the total sample, and males and females separately, we assessed genetic diversity, tested for genetic differentiation between putative populations and isolation by distance, estimated the number of genetic clusters without a priori population information and estimated rates of gene flow using maximum-likelihood and Bayesian approaches. At the ocean basin scale, structure is governed by geographical distance (IBD P < 0.05) and female fidelity to breeding areas, in line with current understanding of the drivers of broadscale population structure. Consistent with previous studies, the Arabian Sea breeding stock was highly genetically differentiated (FST 0.034-0.161; P < 0.01 for all comparisons). However, the breeding stock boundary between west South Africa and east Africa was more porous than expected based on genetic differentiation, cluster and geneflow analyses. Instances of male fidelity to breeding areas and relatively high rates of dispersal for females were also observed between the three substocks in the western Indian Ocean. The relationships between demographic units and current management boundaries may have ramifications for assessments of the status and continued protections of populations still in recovery from commercial whaling.

Factors affecting the incidence of early endoscopic recurrence after ileocolonic resection for Crohn's disease: a multicentre observational study.

AIM: Early endoscopic recurrence is frequently observed in patients following resection for Crohn's disease (CD). However, factors affecting the incidence of an early postoperative endoscopic recurrence (EPER) have not been fully determined. The aim of this study was to evaluate risk factors for EPER after ileocolonic resection for CD. METHOD: This was a retrospective, international multicentre study, in which 127 patients with a first ileocolonoscopy conducted between 6 and 12 months after ileocolonic resection for CD were included. Endoscopic recurrence was defined as a Rutgeerts score of ≥ i2. The following variables were investigated as potential risk factors for EPER: gender, age at surgery, location and behaviour of CD, smoking, concomitant perianal lesions, preoperative use of steroids, immunomodulators and biologics, previous resection, blood transfusion, surgical procedure (open vs laparoscopic approach), length of resected bowel, type of anastomosis (side-to-side vs end-to-end), postoperative complications, granuloma and postoperative biological therapy. Variables related to the patient, disease and surgical procedure were investigated as potential risk factors for EPER, with univariate and multivariate (logistic regression) analyses. RESULTS: 43/127 (34%) patients had EPER at the time of the first postoperative ileocolonoscopy. In univariate analysis, only preoperative steroid use was significantly associated with a higher rate of EPER [21/45 patients (47%) on steroids and 22/82 patients (27%) without steroids (P = 0.04)]. In multivariate analysis, only preoperative steroid use was a significant independent risk factor for EPER (odds ratio 3.28, 95% confidence interval: 1.30-8.28; P = 0.01). CONCLUSIONS: This study found that only preoperative steroid use was a significant risk factor for EPER after ileocolonic resection for CD. Prospective studies are necessary to evaluate precisely the impact of perioperative medications on EPER rates.

Diagnosis and treatment of inflammatory bowel disease: First Latin American Consensus of the Pan American Crohn's and Colitis Organisation. / Diagnóstico y tratamiento de la enfermedad inflamatoria intestinal: Primer Consenso Latinoamericano de la Pan American Crohn's and Colitis Organisation.

The incidence and prevalence of inflammatory bowel disease (IBD) has increased in recent years in several Latin American countries. There is a need to raise awareness in gastroenterologists and the population in general, so that early diagnosis and treatment of ulcerative colitis (UC) and Crohn's Disease (CD) can be carried out. It is important for all physicians to have homogeneous criteria regarding the diagnosis and treatment of IBD in Latin America. The Pan American Crohn's and Colitis Organisation (PANCCO) is an organization that aims to include all the countries of the Americas, but it specifically concentrates on Latin America. The present Consensus was divided into two parts for publication: 1) Diagnosis and treatment and 2) Special situations. This is the first Latin American Consensus whose purpose is to promote a perspective adapted to our Latin American countries for the diagnosis, treatment, and monitoring of patients with UC and CD.

Special situations in inflammatory bowel disease: First Latin American consensus of the Pan American Crohn's and Colitis Organisation (PANCCO) (Second part). / Situaciones especiales en la enfermedad inflamatoria intestinal: primer consenso latinoamericano de la Pan American Crohn's and Colitis Organisation (PANCCO) (Segunda parte).

This is the first Latin American Consensus of the Pan American Crohn's and Colitis Organisation (PANCCO) regarding special situations in patients with inflammatory bowel disease (IBD). The aim of this consensus is to raise awareness in the medical community in all Latin American countries with respect to pregnancy, vaccinations, infections, neoplasms, including colorectal cancer, and pediatric issues in patients with IBD.

Update of the PANCCO clinical practice guidelines for the treatment of ulcerative colitis in the adult population.

Ulcerative colitis (US) is a chronic disease of unknown etiology. It is incurable and its clinical course is intermittent, characterized by periods of remission and relapse. The prevalence and incidence of the disease has been increasing worldwide. The update presented herein includes the participation of healthcare professionals, decision-makers, and a representative of the patients, all of whom declared their conflicts of interest. Answerable clinical questions were formulated, and the outcomes were graded. The information search was conducted on the Medline/PubMed, Embase, Epistemonikos, and LILACS databases, and covered grey literature sources, as well. The search was updated on November 30, 2020, with no restrictions regarding date or language. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) classification system was implemented to establish the strength of the recommendation and quality of evidence. A formal consensus was developed, based on the RAND/UCLA methodology and the document was peer reviewed. The short version of the Clinical Practice Guidelines for the Treatment of Ulcerative Colitis in the Adult Population is presented herein, together with the supporting evidence and respective recommendations. In mild-to-moderate UC, budesonide MMX is an option when treatment with 5-ASA fails, and before using systemic steroids. In moderate-to-severe UC, infliximab, adalimumab, vedolizumab, ustekinumab, and tofacitinib can be used as first-line therapy. If there is anti-TNF therapy failure, ustekinumab and tofacitinib provide the best results. In patients with antibiotic-refractory pouchitis, anti-TNFs are the treatment of choice.

The spectrum of orofacial clefts and treatment logistics at Universitas Academic Hospital, Bloemfontein, South Africa.

BACKGROUND: Cleft lips and/or palates should be identified early and be operated on at specific ages according to international recommendations. In African countries, however, cleft lip and palate surgeries are often delayed. METHODS: A retrospective, descriptive study was done to determine the distribution, specific time delays, demographics and loss to follow-up of patients with cleft lip and/or palates treated at Universitas Academic Hospital over a 10-year period. Data was obtained from outpatient files from the Plastic and Reconstructive Surgery Department at Universitas Academic Hospital. Two hundred and three of 318 records (63.8%) had the defined variables documented. RESULTS: The median time from first presentation to specialist consultation was 1.9 months. The median ages for first presentation was 2.2 months and for specialist consultation 5.2 months. Patients mainly had isolated cleft palates (42.4%), followed by both cleft lip and palate (31%) and isolated cleft lips (24.6%). A quarter of patients (25.6%) were lost to follow-up. More than a third (36.5%) of patients were referred from the local Motheo district and 12.8% were referred from Lesotho. CONCLUSION: In our setting, patients with cleft lip and/or palate are generally diagnosed and referred late. These patients also have delayed access to specialist consultation. Often patients are only evaluated by specialists at ages whereby they should have already undergone their first surgeries. Too many patients are lost to follow-up.

(N-Benzoyl-N'-phenyl-thio-urea-κS)chlorido(η-1,5-cyclo-octa-diene)rhodium(I).

The title compound, [RhCl(C(8)H(12))(C(14)H(12)N(2)OS)], is a rhodium(I) derivative with a functionalized thio-urea ligand. Despite the presence of several heteroatoms, the thio-urea ligand coordinates only in a monodentate fashion via the S atom. The geometry of the coordination sphere is approximately square planar about the Rh(I) atom, with two bonds to the π-electrons of the 1,5-cyclo-octa-diene ligand, one bond to the Cl(-) ligand and one bond to the S atom of the thio-urea ligand. The mol-ecular structure is stabilized by intra-molecular N-H⋯O and N-H⋯Cl hydrogen bonding. Inter-molecular N-H⋯O hydrogen-bonding inter-actions lead to the formation of layers extending parallel to (011).

Darvadstrocel for the treatment of patients with perianal fistulas in Crohn's disease.

Despite significant advances in medical and surgical therapy for perianal fistulas in Crohn's disease (CD), treatment results are still modest, and a specific need for more effective therapies is a reality. Darvadstrocel is composed of expanded human allogeneic mesenchymal adult stem cells extracted from adipose tissue and constitutes the first stem cell therapy for perianal fistulizing CD to receive approval from the European Medicines Agency (EMA). This therapy is injected in both internal and external openings, as well as inside the fistula tracks, to induce fistula healing. In this monograph, the authors review the preclinical pharmacology of darvadstrocel, as well as pharmacokinetics and metabolism, and cover the main indications and detailed information on the efficacy and safety profile of the agent. Possible interactions with other agents used to treat CD are also explored. Darvadstrocel is a safe and effective therapy for perianal complex fistulas in CD, and represents the beginning of a new era of mesenchymal stem cell therapy in this difficult phenotype of the disease.

Dive behaviour and foraging effort of female Cape fur seals Arctocephalus pusillus pusillus.

While marine top predators can play a critical role in ecosystem structure and dynamics through their effects on prey populations, how the predators function in this role is often not well understood. In the Benguela region of southern Africa, the Cape fur seal (Arctocephalus pusillus pusillus) population constitutes the largest marine top predator biomass, but little is known of its foraging ecology other than its diet and some preliminary dive records. Dive information was obtained from 32 adult females instrumented with dive recorders at the Kleinsee colony (29°34.17' S, 16°59.80' E) in South Africa during 2006-2008. Most dives were in the depth range of epipelagic prey species (less than 50 m deep) and at night, reflecting the reliance of Cape fur seals on small, vertically migrating, schooling prey. However, most females also performed benthic dives, and benthic diving was prevalent in some individuals. Benthic diving was significantly associated with the frequency with which females exceeded their aerobic dive limit. The greater putative costs of benthic diving highlight the potential detrimental effects to Cape fur seals of well-documented changes in the availability of epipelagic prey species in the Benguela.

Successful provision of inter-hospital extracorporeal cardiopulmonary resuscitation for acute post-partum pulmonary embolism.

Mortality during pregnancy in a well-resourced setting is rare, but acute pulmonary embolism is one of the leading causes. We present the successful use of extracorporeal cardiopulmonary resuscitation (eCPR) in a 22-year old woman who experienced cardiopulmonary collapse following urgent caesarean section in the setting of a sub-massive pulmonary embolus. Resources and personnel to perform eCPR were not available at the maternity hospital and were recruited from an adjacent pediatric hospital. Initial care used low blood flow extracorporeal membrane oxygenation (ECMO) with pediatric ECMO circuitry, which was optimized when the team from a nearby adult cardiac hospital arrived. Following ECMO support, the patient experienced massive hemorrhage which was managed with uterotonic agents, targeted transfusion, bilateral uterine artery embolisation and abdominal re-exploration. The patient was transferred to an adult unit where she remained on ECMO for five days. She was discharged home with normal cognitive function. This case highlights the role ECMO plays in providing extracorporeal respiratory or mechanical circulatory support in a high risk obstetric patient.

Randomised comparison of three types of continuous anterior abdominal wall block after midline laparotomy for gynaecological oncology surgery.

Effective analgesia after midline laparotomy surgery is essential for enhanced recovery programs. We compared three types of continuous abdominal wall block for analgesia after midline laparotomy for gynaecological oncology surgery. We conducted a single-centre, double-blind randomised controlled trial. Ninety-four patients were randomised into three groups to receive two days of programmed intermittent boluses of ropivacaine (18 ml 0.5% ropivacaine every four hours) via either a transversus abdominis plane (TAP) catheter, posterior rectus sheath (PRS) catheter, or a subcutaneous (SC) catheter. All groups received patient-controlled analgesia with morphine, and regular paracetamol and non-steroidal anti-inflammatory medication. Measured outcomes included analgesic and antiemetic usage and visual analog scores for pain, nausea, vomiting, and satisfaction. Eighty-eight patients were analysed (29 SC, 29 PRS and 30 TAP). No differences in the primary outcome were found (median milligrams morphine usage on day two SC 28, PRS 25, TAP 21, P=0.371). There were differences in secondary outcomes. Compared with the SC group, the TAP group required less morphine in recovery (0 mg versus 6 mg, P=0.01) and reported less severe pain on day one (visual analog scores 36.3 mm versus SC 55 mm, P=0.04). The TAP group used fewer doses of tropisetron on day one compared with the PRS group (8 versus 21, P=0.016). Programmed intermittent boluses of ropivacaine delivered via PRS, TAP and SC catheters can be provided safely to patients undergoing midline laparotomy surgery. Initially TAP catheters appear superior, reducing early opioid and antiemetic requirements and severe pain, but these advantages are lost by day two.

Heteroditopic P,N ligands in gold(I) complexes: synthesis, structure and cytotoxicity.

New heteroditopic, bi- and multidentate imino- and aminophosphine ligands were synthesised and complexed to [AuCl(THT)] (THT=tetrahydrothiophene). X-ray crystallography confirmed Schiff base formation in three products, the successful reduction of the imino-group to the sp(3)-hybridised amine in several instances, and confirmed the formation of mono-gold(I) imino- and aminophosphine complexes for four Au-complexes. Cytotoxicity studies in cancerous and non-cancerous cell lines showed a marked increase in cytotoxicity upon ligand complexation to gold(I). These findings were supported by results from the 60-cell line fingerprint screen of the Developmental Therapeutics Programme of the National Institutes of Health for two promising compounds. The cytotoxicity of some of these ligands and gold(I)complexes is due to the induction of apoptosis. The ligands and gold(I)complexes demonstrated selective toxicity towards specific cell lines, with Jurkat T cells being more sensitive to the cytotoxic effects of these compounds, while the non-cancerous human cell line KMST6 proved more resistant when compared to the cancerous cell lines. Results from the NIH DTP 60 cell-line fingerprint screen support the observed enhancement of cytotoxicity upon gold(I) complexation. One gold(I)complex induced high levels of apoptosis at concentrations of 50 µM in all the cell lines screened in this study, while some of the other compounds selectively induced apoptosis in the cell lines. These results point towards the potential for selective toxicity to cancerous cells through the induction of apoptosis.

Islet cell research brings hope for a diabetes cure: meeting report from the 6(th) annual islet society meeting in Stellenbosch, South Africa.

The International Diabetes Federation predicts that, over the next twenty years, the largest increase in the prevalence of diabetes will be in the Africa region. Recognizing an unmet need for more focus on Africa and engagement with African scholars, the Islet Society held its 6th annual meeting July 20-21, 2014 in Stellenbosch, South Africa. Here, we present a report that covers the presentations and discussion points from that meeting. Work was presented on a variety of topics and included presentations by a significant proportion of Africa diabetes researchers. Overall, it was an excellent conference, with many new international collaborations initiated. We hope that other groups will also respond to the need for more conferences in Africa and focused on Africa.