Confirmation and refutation of very luminous galaxies in the early Universe.

During the first 500 million years of cosmic history, the first stars and galaxies formed, seeding the Universe with heavy elements and eventually reionizing the intergalactic medium1-3. Observations with the James Webb Space Telescope (JWST) have uncovered a surprisingly high abundance of candidates for early star-forming galaxies, with distances (redshifts, z), estimated from multiband photometry, as large as z ≈ 16, far beyond pre-JWST limits4-9. Although such photometric redshifts are generally robust, they can suffer from degeneracies and occasionally catastrophic errors. Spectroscopic measurements are required to validate these sources and to reliably quantify physical properties that can constrain galaxy formation models and cosmology10. Here we present JWST spectroscopy that confirms redshifts for two very luminous galaxies with z > 11, and also demonstrates that another candidate with suggested z ≈ 16 instead has z = 4.9, with an unusual combination of nebular line emission and dust reddening that mimics the colours expected for much more distant objects. These results reinforce evidence for the early, rapid formation of remarkably luminous galaxies while also highlighting the necessity of spectroscopic verification. The large abundance of bright, early galaxies may indicate shortcomings in current galaxy formation models or deviations from physical properties (such as the stellar initial mass function) that are generally believed to hold at later times.

Joint ACPGBI and The Duke's Club statement on colonoscopy training.

Colorectal surgeons across the UK currently undertake a large proportion of routine diagnostic and therapeutic colonoscopy in most NHS Trusts [1]. Meanwhile, the new UK General Surgical curriculum now includes an indicative requirement of 200 diagnostic colonoscopies for surgical trainees who have declared a colorectal subspecialty interest (hereafter termed 'colorectal trainees'), indicating the JCST's (Joint Committee on Surgical Training) commitment to colonoscopy training. However, several studies have reported a marked deficiency in colonoscopy training opportunities and accreditation for surgical trainees compared with gastroenterology trainees [2-4].

Does Including Dexmedetomidine Improve Outcomes After Intravenous Sedation for Outpatient Dentoalveolar Surgery?

PURPOSE: Dexmedetomidine represents an intriguing adjunct to outpatient intravenous (IV) sedation owing to its decreased risk of respiratory depression. The purpose of the present study was to measure the incremental effect of incorporating dexmedetomidine (DXM) into an established IV sedation regimen compared with control IV sedation without the DXM infusion. MATERIALS AND METHODS: We designed a prospective, controlled trial in which American Society of Anesthesiologists Class 1 and 2 patients requiring both maxillary and mandibular dentoalveolar surgery would undergo 2 sedation appointments: 1 arch treated with surgery with control sedation (DXM-) using midazolam, fentanyl, and propofol as needed, and a second surgery on the opposite arch using the experimental sedation regimen (DXM+) of midazolam, fentanyl, and propofol, as needed, and a DXM infusion at 4 µg/kg/hr. The surgeon was the same for every appointment, and the patients were kept unaware regarding which sedation had included the experimental regimen. Whether the experimental sedation was used at the first or second surgery was randomized. The primary measured outcomes were efficiency in terms of anesthesia time for each sedation, the physiologic response in terms of vital signs, and the subjective patient experience. RESULTS: A total of 12 patients completed the trial. With DXM-, the patients had significantly shorter total (∼15 minutes) and adjusted anesthesia (∼10 minutes) times. With DXM+, the patients had significantly lower average systolic blood pressure (SBP), SBP low values, diastolic blood pressure (DBP) low values, average heart rate (HR), and HR low values. None of the other continuous patient outcomes differed significantly between the 2 groups. Of the 12 patients, 10 (83.3%) reported that they preferred the experimental sedation experience with DXM (95% confidence interval, 0.52 to 0.98). CONCLUSIONS: Using a DXM infusion with outpatient dentoalveolar surgery allowed for acceptable levels of sedation, greater patient satisfaction, and longer anesthesia and appointment times and often resulted in lower BP and heart rate.

Robo4 vaccines induce antibodies that retard tumor growth.

Tumor endothelial specific expression of Robo4 in adults identifies this plasma membrane protein as an anti-cancer target for immunotherapeutic approaches, such as vaccination. In this report, we describe how vaccination against Robo4 inhibits angiogenesis and tumor growth. To break tolerance to the auto-antigen Robo4, mice were immunised with the extracellular domain of mouse Robo4, fused to the Fc domain of human immunoglobulin within an adjuvant. Vaccinated mice show a strong antibody response to Robo4, with no objectively detectable adverse effects on health. Robo4 vaccinated mice showed impaired fibrovascular invasion and angiogenesis in a rodent sponge implantation assay, as well as a reduced growth of implanted syngeneic Lewis lung carcinoma. The anti-tumor effect of Robo4 vaccination was present in CD8 deficient mice but absent in B cell or IgG1 knockout mice, suggesting antibody dependent cell mediated cytotoxicity as the anti-vascular/anti-tumor mechanism. Finally, we show that an adjuvant free soluble Robo4-carrier conjugate can retard tumor growth in carrier primed mice. These results point to appropriate Robo4 conjugates as potential anti-angiogenic vaccines for cancer patients.

Posttraumatic arteriovenous malformation of the face: a case report.

BACKGROUND: Head and neck arteriovenous malformations (AVMs) are reported to occur in 0.1% of the population. Extracranial AVMs account for only 8.1% of head and neck AVMs. Of these, traumatically acquired AVMs of the face are generally reported as quite rare. When secondary to trauma, the lesion is usually supplied by a single vessel, as compared to the multiple vessels often seen with congenital etiology. OBJECTIVES: Understanding of regional anatomy is paramount when assessing and managing facial injuries. As an integral health care provider for the facial trauma patient, it is the responsibility of the emergency physician to recognize this rare pathologic lesion necessary to coordinate surgical management of the traumatic AVM. CASE REPORT: We present a case report of a patient who sustained a facial laceration complicated by the development of a vascular malformation. The facial laceration in this case report highlights the complexity of wound evaluation and management when treating patients in the emergency department. CONCLUSION: Traumatic AVMs are quite rare in the head and neck and are mostly seen in the extremities. Although rare, they have been reported after typical facial trauma as well as elective surgical procedures. The management of such lesions may include selective embolization or surgical exploration with ligation. Emergency physicians and facial trauma surgeons are challenged with recognizing and treating these rare but very real vascular lesions. It is our hope that this case report provides an overview of posttraumatic AVMs in the head and neck.

Delayed enterocutaneous fistula formation secondary to an inverted non-absorbable suture post midline laparotomy closure.

INTRODUCTION: Enterocutaneous fistula is a well recognised complication of intra-abdominal surgery. Postoperatively, it may occur due to a small bowel injury or an anastomotic leak and usually presents within days or weeks after surgery. METHODS: We present a case report. Information was obtained through a retrospective review of the notes, clinic letters, images and the histology report. RESULTS: We present a case of a patient who developed an enterocutaneous fistula 34 years after panproctocolectomy for ulcerative colitis. Imaging was consistent with an enterocutaneous fistula arising from mid-small bowel. A laparotomy and small bowel resection was performed. The enterocutaneous fistula occurred due to an inverted non-absorbable suture post midline laparotomy closure. CONCLUSION: Suture-related enterocutaneous fistula can be a rare delayed complication of a midline laparotomy closure when a knot is inverted intra-peritoneally. Consideration should be given to either leaving a knot in the subcutaneous fat tissue or feeding it between the rectus sheath and the suture bites.

Advances in head and neck radiotherapy to the mandible.

Management of radiation-exposed bone in the mandible is a dilemma many oral and maxillofacial surgeons must confront and manage. Current advances in radiotherapy techniques using pin-point computerized accuracy in combination with other advances, such as morphed imaging, fractionalization protocols, minimization of scatter, and pretreatment dental examinations, have greatly decreased the late effects of radiation and osteoradionecrosis. The intent of this article is to provide a brief overview of the following topics: radiotherapy physics and radiobiology, effects of radiotherapy on normal tissues, including the pathogenesis of osteoradionecrosis, and advances in contemporary radiotherapy treatment.

Glutamate dependent NMDA receptor 2D is a novel angiogenic tumour endothelial marker in colorectal cancer.

Current vascular-targeted therapies in colorectal cancer (CRC) have shown limited benefit. The lack of novel, specific treatment in CRC has been hampered by a dearth of specific endothelial markers. Microarray comparison of endothelial gene expression in patient-matched CRC and normal colon identified a panel of putative colorectal tumour endothelial markers. Of these the glutamate dependent NMDA receptor GRIN2D emerged as the most interesting target. GRIN2D expression was shown to be specific to colorectal cancer vessels by RTqPCR and IHC analysis. Its expression was additionally shown be predictive of improved survival in CRC. Targeted knockdown studies in vitro demonstrated a role for GRIN2D in endothelial function and angiogenesis. This effect was also shown in vivo as vaccination against the extracellular region of GRIN2D resulted in reduced vascularisation in the subcutaneous sponge angiogenesis assay. The utility of immunologically targeting GRIN2D in CRC was demonstrated by the vaccination approach inhibiting murine CRC tumour growth and vascularisation. GRIN2D represents a promising target for the future treatment of CRC.

MCAM and LAMA4 Are Highly Enriched in Tumor Blood Vessels of Renal Cell Carcinoma and Predict Patient Outcome.

The structure and molecular signature of tumor-associated vasculature are distinct from those of the host tissue, offering an opportunity to selectively target the tumor blood vessels. To identify tumor-specific endothelial markers, we performed a microarray on tumor-associated and nonmalignant endothelium collected from patients with renal cell carcinoma (RCC), colorectal carcinoma, or colorectal liver metastasis. We identified a panel of genes consistently upregulated by tumor blood vessels, of which melanoma cell adhesion molecule (MCAM) and its extracellular matrix interaction partner laminin alpha 4 (LAMA4) emerged as the most consistently expressed genes. This result was subsequently confirmed by immunohistochemical analysis of MCAM and LAMA4 expression in RCC and colorectal carcinoma blood vessels. Strong MCAM and LAMA4 expression was also shown to predict poor survival in RCC, but not in colorectal carcinoma. Notably, MCAM and LAMA4 were enhanced in locally advanced tumors as well as both the primary tumor and secondary metastases. Expression analysis in 18 different cancers and matched healthy tissues revealed vascular MCAM as highly specific in RCC, where it was induced strongly by VEGF, which is highly abundant in this disease. Lastly, MCAM monoclonal antibodies specifically localized to vessels in a murine model of RCC, offering an opportunity for endothelial-specific targeting of anticancer agents. Overall, our findings highlight MCAM and LAMA4 as prime candidates for RCC prognosis and therapeutic targeting. Cancer Res; 76(8); 2314-26. ©2016 AACR.

The future of surgical training in the context of the 'Shape of Training' Review: Consensus recommendations by the Association of Surgeons in Training.

ASiT has long maintained that in order to provide the best quality care to patients in the UK and Republic of Ireland, it is critical that surgeons are trained to the highest standards. In addition, it is imperative that surgery remains an attractive career choice, with opportunities for career progression and job satisfaction to attract and retain the best candidates. In 2013, the Shape of Training review report set out recommendations for the structure and delivery of postgraduate training in light of an ever increasingly poly-morbid and ageing population. This consensus statement outlines ASIT's position regarding recommendations for improving surgical training and aims to help guide discussions with regard to future proposed changes to surgical training.

Management of intestinal obstruction in advanced malignancy.

Patients with incurable, advanced abdominal or pelvic malignancy often present to acute surgical departments with symptoms and signs of intestinal obstruction. It is rare for bowel strangulation to occur in these presentations, and spontaneous resolution often occurs, so the luxury of time should be afforded while decisions are made regarding surgery. Cross-sectional imaging is valuable in determining the underlying mechanism and pathology. The majority of these patients will not be suitable for an operation, and will be best managed in conjunction with a palliative medicine team. Surgeons require a good working knowledge of the mechanisms of action of anti-emetics, anti-secretories and analgesics to tailor early management to individual patients, while decisions regarding potential surgery are made. Deciding if and when to perform operative intervention in this group is complex, and fraught with both technical and emotional challenges. Surgery in this group is highly morbid, with no current evidence available concerning quality of life following surgery. The limited evidence concerning operative strategy suggests that resection and primary anastomosis results in improved survival, over bypass or stoma formation. Realistic prognostication and involvement of the patient, care-givers and the multidisciplinary team in treatment decisions is mandatory if optimum outcomes are to be achieved.

Ultraviolet luminosity density of the universe during the epoch of reionization.

The spatial fluctuations of the extragalactic background light trace the total emission from all stars and galaxies in the Universe. A multiwavelength study can be used to measure the integrated emission from first galaxies during reionization when the Universe was about 500 million years old. Here we report arcmin-scale spatial fluctuations in one of the deepest sky surveys with the Hubble Space Telescope in five wavebands between 0.6 and 1.6 µm. We model-fit the angular power spectra of intensity fluctuation measurements to find the ultraviolet luminosity density of galaxies at redshifts greater than 8 to be log ρ(UV) = 27.4(+0.2)(-1.2) ergs(-1) Hz(-1) Mpc(-3) (1σ). This level of integrated light emission allows for a significant surface density of fainter primeval galaxies that are below the point-source detection level in current surveys.

AAOMP case challenge: "The case of a subtle expansion of the mandible".

A healthy 25-year old Caucasian man presented for a routine dental examination. He was unaware of a subtle expansion involving the right posterior mandible, which was bony hard and nontender. Radiographic findings prompted an immediate referral of the patient to an oral and maxillofacial surgeon for diagnosis and management of the jaw lesion. What is your diagnosis?

A multicentre cohort study assessing day of week effect and outcome from emergency appendicectomy.

BACKGROUND: There is evidence to suggest that patients undergoing treatment at weekends may be subject to different care processes and outcomes compared with weekdays. This study aimed to determine whether clinical outcomes from weekend appendicectomy are different from those performed on weekdays. METHOD: Multicentre cohort study during May-June 2012 from 95 centres (89 within the UK). The primary outcome was the 30-day adverse event rate. Multilevel modelling was used to account for clustering within hospitals while adjusting for case mix to produce adjusted ORs and 95% CIs. RESULTS: When compared with Monday, there were no significant differences for other days of the week considering 30-day adverse events in adjusted models. On Sunday, rates of simple appendicitis were highest, and rates of normal (OR 0.62, 95% CI 0.42 to 0.90) and complex appendicitis (OR 0.65, 95% CI 0.46 to 0.93) lowest. This was accompanied by a 43% lower likelihood in use of laparoscopy on Sunday (OR 0.47, 95% CI 0.32 to 0.69), accompanied by the lowest level of consultant presence for the week. When pooling weekends and weekdays, laparoscopy use remained less likely at the weekend (OR 0.68, 95% CI 0.55 to 0.83), with no significant difference for 30-day adverse event rate (OR 1.01, 95% CI 0.80 to 1.29). CONCLUSIONS: This study found that weekend appendicectomy was not associated with increased 30-day adverse events. It cannot rule out smaller increases that may be shown by larger studies. It further illustrated that patients operated on at weekends were subject to different care processes, which may expose them to risk.

Perforation of Meckel's diverticulum secondary to a large faecolith.

A 79-year-old woman presented with a 4 day history of central abdominal pain and vomiting. Clinical examination revealed a distended abdomen with predominantly right sided tenderness. Following an initial period of supportive treatment pending further imaging, evolving abdominal signs became evident. Based on the suspicion of a perforated hollow viscus, an emergency laparotomy was carried out. Operative findings were of a Meckel's diverticulum with evidence of pressure necrosis and perforation near its apex, which was distended due to a 6 cm faecolith. Resection and primary anastomosis was performed. Despite a lower respiratory tract infection, the patient was deemed clinically stable enough to be discharged on the 24th postoperative day.

Dental care for patients with heart failure: an update.

BACKGROUND: Heart failure (HF) is a common clinical syndrome that affects an estimated 5.7 million Americans. It is a growing health problem, particularly in people 65 years or older. Therefore, the probability that dental practitioners will have patients who have HF is increasing. METHODS: The authors reviewed medical literature from 2000 through 2009 to determine the incidence, classifications, pathophysiology and advances in the medical diagnosis and treatment of HF. They also reviewed available dental literature during the same period to formulate treatment recommendations for dental care of people who have HF. RESULTS: Medicine has made advances in understanding and treating HF. These advances have resulted in the development of revised classification systems, a more structured approach to patient assessment and improved therapeutic options. CONCLUSIONS: Dentists need to be aware of advances in the diagnosis and treatment of HF. Keeping in mind the potential for morbidity in patients who have HF, identifying and accurately assessing these patients is imperative for clinical management. CLINICAL IMPLICATIONS: Often it is necessary for dentists to consult with patients' physicians to coordinate care and determine whether treatment can be rendered appropriately in a routine dental setting or whether advanced support, monitoring or both are necessary.

Gallbladder torsion presenting as chest pain.

While acute torsion of the gallbladder is an uncommon pathology, as this case demonstrates, it can present with sudden onset of chest pain, and must be borne in mind as a differential diagnosis in this patient demographic if early recognition and definitive management are to be made possible.