Prophylactic Central Compartment Dissection on the Long-Term Outcome of Advanced (N0-T3/T4) Papillary Thyroid Cancer.

Aim: To see whether prophylactic central compartment dissection is recommended for advanced papillary thyroid cancer or as part of selective neck node dissection. Central compartment dissection is a technically demanding surgical procedure and carries a higher incidence of complications. The present retrospective case-control study analysed the impact of prophylactic central compartment dissection on the long-term outcome of advanced (N0-T3/T4) papillary thyroid cancer. Materials and methods: Case records of patients operated on for papillary thyroid cancer from 2005 to 2010 were reviewed and patients with Tumour stage 3-4 and N0 nodal status were included in the study. The institutional protocol was to perform total thyroidectomy with central compartment dissection during the early phase of the study period (2005 to 2008) but this strategy was shifted to total thyroidectomy alone during the latter phase. Fifty-five patients were included in the study and 29 of the cohort had total thyroidectomy with prophylactic central compartment dissection as the primary surgery and the remaining 26 had a total thyroidectomy as the primary surgical procedure. Result: Patients were followed up for a median duration of 115 months and found to have no significant difference in the incidences of loco-regional recurrences between the groups. (n:4 (14%) Vs n: 3 (12%) p = .463). The disease-free survival and overall survival were not significantly different in the groups. There was a trend to an increase in the incidence of permanent hypoparathyroidism in patients who had central compartment dissection. Conclusion: Prophylactic central compartment dissection did not influence the 10-year outcome of advanced node-negative papillary thyroid cancers.

First Direct Measurement of the 64.5 keV Resonance Strength in the

The CNO cycle is one of the most important nuclear energy sources in stars. At temperatures of hydrostatic H-burning (20 MK

Testing quantum electrodynamics in extreme fields using helium-like uranium.

Quantum electrodynamics (QED), the quantum field theory that describes the interaction between light and matter, is commonly regarded as the best-tested quantum theory in modern physics. However, this claim is mostly based on extremely precise studies performed in the domain of relatively low field strengths and light atoms and ions1-6. In the realm of very strong electromagnetic fields such as in the heaviest highly charged ions (with nuclear charge Z ≫ 1), QED calculations enter a qualitatively different, non-perturbative regime. Yet, the corresponding experimental studies are very challenging, and theoretical predictions are only partially tested. Here we present an experiment sensitive to higher-order QED effects and electron-electron interactions in the high-Z regime. This is achieved by using a multi-reference method based on Doppler-tuned X-ray emission from stored relativistic uranium ions with different charge states. The energy of the 1s1/22p3/2 J = 2 → 1s1/22s1/2 J = 1 intrashell transition in the heaviest two-electron ion (U90+) is obtained with an accuracy of 37 ppm. Furthermore, a comparison of uranium ions with different numbers of bound electrons enables us to disentangle and to test separately the one-electron higher-order QED effects and the bound electron-electron interaction terms without the uncertainty related to the nuclear radius. Moreover, our experimental result can discriminate between several state-of-the-art theoretical approaches and provides an important benchmark for calculations in the strong-field domain.

Proton-Capture Rates on Carbon Isotopes and Their Impact on the Astrophysical

The ^{12}C/^{13}C ratio is a significant indicator of nucleosynthesis and mixing processes during hydrogen burning in stars. Its value mainly depends on the relative rates of the ^{12}C(p,γ)^{13}N and ^{13}C(p,γ)^{14}N reactions. Both reactions have been studied at the Laboratory for Underground Nuclear Astrophysics (LUNA) in Italy down to the lowest energies to date (E_{c.m.}=60 keV) reaching for the first time the high energy tail of hydrogen burning in the shell of giant stars. Our cross sections, obtained with both prompt γ-ray detection and activation measurements, are the most precise to date with overall systematic uncertainties of 7%-8%. Compared with most of the literature, our results are systematically lower, by 25% for the ^{12}C(p,γ)^{13}N reaction and by 30% for ^{13}C(p,γ)^{14}N. We provide the most precise value up to now of 3.6±0.4 in the 20-140 MK range for the lowest possible ^{12}C/^{13}C ratio that can be produced during H burning in giant stars.

Segmentation of retinal blood vessels by a novel hybrid technique- Principal Component Analysis (PCA) and Contrast Limited Adaptive Histogram Equalization (CLAHE).

Diabetic Retinopathy is a persistent disease of eyes that may lead to permanent loss of sight. In this paper, methodology is proposed to segment region of interest (ROI) i.e. new blood vessels in fundus images of retina of Diabetic Retinopathy (DR). The database of 50 fundus retinal images of healthy subjects and DR patients is fetched from Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. The experimental set up consists of three set of experiments for the disease. For DR, in the first stage of automated blood vessel segmentation, gray-scale image is produced from the colored image using Principal Component Analysis (PCA) in the preprocessing step. The contrast enhancement by the Contrast Limited Adaptive Histogram Equalization (CLAHE) highlights the retinal blood vessels in the gray-scale image i.e. it unsheathed newly formed retinal blood vessels whereas PCA preserved their texture and color discrimination in DR images. The expert ophthalmologist(s) scrutiny on both internet repository and real time data acted as the gold standard for further analysis and formation of the proposed method. Further, ophthalmologists ascertained the forming of new blood vessels only on the disc region and divulging them, which were impossible with the naked eye. These operations help in extracting retinal blood vessels present on the disc and non-disc region of the image. The comparison of the results are done with the state of art methods like watershed transform. It is observed from the results that the new blood vessels are better segmented by the proposed methodology and are marked by the experienced ophthalmologist for validation. Further, for quantitative analysis, the features are extracted from new blood vessels as they are crucial for scientific interpretation. The results of the features lie in permissible limits such as no. of segments vary from 2 to 5 and length of segments varies from 49 to 164 pixels. Similarly, other features such as gray level of new blood vessels lie in 0.296-0.935 normalized range, coefficient with variations in gray level in the range of 0.658-10.10 and distance from vessel origin lie in the range of 56-82 pixels respectively. Both quantitative and qualitative results show that the methodologies proposed boosted the ophthalmic and clinical diagnosis. The developed method further handled the false detection of vessels near the optic disk boundary, under-segmentation of thin vessels, detection of pathological anomalies such as exudates, micro-aneurysms and cotton wool spots. From the numerical analysis, ophthalmologist extracted the information of number of vessels formed, length of the new vessels, observation that the new vessels appearing are less homogenous than the normal vessels. Also about the new vessels, whether they lie on the centre of disc region or towards its edges. These parameters lie as per the findings of the ophthalmologists on retinal images and automated detection helped in monitoring and comprehensive patient assessment. The experimental results show case that the proposed method has higher sensitivity, specificity and accuracy as compared to state of art methods i.e. 0.9023, 0.9610 and 0.9921, respectively. Similar results are obtained on retinal fundus images of PGIMER Chandigarh with sensitivity-0.9234, specificity-0.9955 and accuracy-0.9682.

A guide for assessing the clinical relevance of findings in small bowel capsule endoscopy: analysis of 8064 answers of international experts to an illustrated script questionnaire.

BACKGROUND AND AIM: Although recommended, the P-score used for assessing the pertinence / relevance of findings seen in small bowel (SB) capsule endoscopy (CE) is based on a low level of knowledge. The aim of this study was to evaluate the clinical relevance of the most frequent SBCE findings through an illustrated script questionnaire. MATERIALS AND METHODS: Sixteen types of SBCE findings were illustrated four times each in three different settings (occult and overt obscure gastrointestinal bleeding and suspected Crohn's disease), and with a variable number (n = 1/n = 2-5/n ≥ 6), thus providing a questionnaire with 192 scenarios and 576 illustrated questions. Fifteen international experts were asked to rate the finding's relevance for each question as very unlikely (-2) / unlikely (-1) / doubtful (0) / likely (+1) / very likely (+2). The median score (≤-0.75, between -0.75 and 0.75, or ≥0.75) obtained for each scenario determined a low (P0), intermediate (P1) or high (P2) relevance, respectively. RESULTS: 8064 answers were analyzed. Participation and completion rates were 93% and 100%, respectively. In overt or occult OGIB, resultant P2 findings were 'typical angiectasia', 'deep ulceration', 'stenosis', and'blood', whatever their numbers, and 'superficial ulcerations' when multiple. While in suspected CD, consensus P2 lesions were 'deep ulceration' and 'stenosis' whatever their numbers, and 'aphthoid erosions' and 'superficial ulcerations' when multiple. CONCLUSION: This study establishes a guide for the evaluation of relevance of SBCE findings. It represents a step forward for SB-CE interpretation and is intended to be used as a tool for teaching and academic research.

Double-headed small-bowel capsule endoscopy: Real-world experience from a multi-centre British study.

INTRODUCTION: Capsule endoscopy (CE) is well established the investigation of small-bowel (SB) pathology. We compared the use of double-headed (DH) capsules, to conventional single-headed (SH), in a real-world patient cohort in the first multicentre British study. METHODS: Over 9 months, patients referred for routine SBCE at 4 tertiary referral centres in the UK underwent DH CE instead of conventional SH using MiroCamⓇ MC2000 as per local protocols. One head (L/R) was chosen at random and reported by an expert reviewer. The DH recordings, anonymised and randomised, reported by another expert or re-read after a 4-week interval. For each CE, numbers and types of findings and overall conclusion/diagnosis were compared between SH and DH examinations. RESULTS: 211 CEs were performed. 7 failed to reach the SB; 204 analysed. Indications were: SB bleeding (n = 94); ?SB inflammation or reassessment of known inflammatory bowel disease (IBD) (n = 84); ?SB neoplasia including suspicious radiological imaging (n = 15); and, others e.g. ?celiac disease (n = 11). For SB bleeding: 27/94 (28.7%) examinations reported differences between SH and DH readings. In 17 (18.1%) the findings were clinically significant. SH CE missed angiectasias (5 pts), SB inflammation (7 pts), oesophagitis (2 pts) and SB masses (2 pts). In 1 patient, the extent of angiectasias seen was greater on the DH reading. For IBD: findings differed in 30/84 (35.7%) of CEs; 11 (13.1%) were clinically significant. In 5, signs of active inflammation were missed by the SH reading. In 6, assessment of extent/severity differed. For?SB neoplasia findings differed in 2/15 (13.3%) of examinations. Both were clinically significant. For others: 1/11 (9.1%) examinations differed; however, not deemed clinically significant. Overall, use of DH CE impacted the diagnosis in 30/204 (14.7%). CONCLUSIONS: The use of DH CE provides more information with the potential to change clinical diagnosis and therefore management. Therefore, the routine adoption of DH CE in SB assessment should be considered.

Cytotoxic Lesion of the Corpus Callosum in an Adolescent with Multisystem Inflammatory Syndrome and SARS-CoV-2 Infection.

Multisystem inflammatory syndrome in children is a recently described complication in the late phase of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection involving systemic hyperinflammation and multiorgan dysfunction. The extent of its clinical picture is actively evolving and has yet to be fully elucidated. While neurologic manifestations of SARS-CoV-2 are well-described in the adult population, reports of neurologic complications in pediatric patients with SARS-CoV-2 infection are limited. We present a pediatric patient with SARS-CoV-2 infection with development of multisystem inflammatory syndrome and acute encephalopathy causing delirium who was found to have a cytotoxic lesion of the corpus callosum on neuroimaging. Cytotoxic lesions of the corpus callosum are a well-known, typically reversible entity that can occur in a wide range of conditions, including infection, seizure, toxins, nutritional deficiencies, and Kawasaki disease. We hypothesized that the cytotoxic lesion of the corpus callosum, in the index case, was secondary to the systemic inflammation from SARS-CoV-2 infection, resulting in multisystem inflammatory syndrome in children.

What is the role of small bowel capsule endoscopy in established coeliac disease?

INTRODUCTION: Patients with established coeliac disease (CD) can present with signs and symptoms requiring small bowel capsule endoscopy (SBCE) to assess for persistent disease beyond the duodenum and to rule out complications. There is paucity of data on extent of disease on SBCE in relation to histology, clinical and serological parameters. The aim of this study was to assess the relationship between symptoms, CD serology and Marsh classification of disease and extent of disease on SBCE in patients with established CD. METHODS: Hundred patients with established CD and 200 controls underwent a SBCE. SBCEs were reviewed by expert reviewers. Extent of disease on SBCE, CD findings and small bowel transit were recorded. RESULTS: Considering duodenal histology (D2; Marsh 3a or above) as the gold standard for diagnosing CD activity, the sensitivity of SBCE to delineate active disease was 87.2%. The specificity was 89.0%. Age at SBCE (P=0.006), albumin (P=0.004) and haemoglobin (P=0.0001), Marsh score of histology from the duodenal bulb (D1) (P=0.0001) and the second part of the duodenum (P=0.0001), refractory CD (P=0.007) on histology correlated with extent of affected small bowel (SB) mucosa on univariate analysis. On multiple regression analysis, albumin (P=0.036) and Marsh score of histology (D1) (P=0.019), vitamin B12 (P=0.001) and folate levels (P=0.008) were statistically significant. Extent of affected SB mucosa (11.0% vs 1.35%) was greater in patients with complications including those with refractory CD (P=0.008). CONCLUSIONS: This is the first study showing correlation between extent of disease and severity of duodenal histology, markers of malabsorption such as folate levels and vitamin B12 and complications of CD.

Mapping the landscape of cataract surgery teaching assessment in Canadian residency programs.

OBJECTIVE: The Royal College of Physicians and Surgeons of Canada has mandated a shift in post-graduate residency education in Canada towards a competency-based model. Within this context, it is unclear how resident's competence in cataract surgery is currently being assessed for both formative and summative purposes. Therefore, we conducted a national survey to evaluate the current landscape of cataract surgery teaching in Canadian Ophthalmology programs. METHODS: The opportunity to participate in an online survey was extended to all Canadian ophthalmology program directors and residents. Between July and September 2017, data was collected on demographics (name of program, levels of training), current framework of assessment, and any other contexts for cataract surgery assessments being used (e.g., wetlabs or surgical simulators). RESULTS: We had a total of 32 responses including 7 program directors (22%), 14 senior residents (44%), and 10 junior residents (34%). The assessments used varied greatly; none of the residency programs used a published assessment tool for assessing skill in cataract surgery. The majority of programs (9 of 11; 82%) used locally-designed assessments and two programs (18%) did not use any standardized forms or tools. All schools were using a wet lab to augment surgical teaching and simulators were being used by 5 of 11 programs (45%). CONCLUSION: There are a variety of approaches being used to assess competence in cataract surgery. Many programs share some similarities, and a framework for designing assessment is suggested to guide future efforts at competency-based training and assessment.

Gut Sphingolipid Composition as a Prelude to Necrotizing Enterocolitis.

Necrotizing enterocolitis (NEC) remains a major challenge in neonatology. Little is known about NEC pathophysiology apart from the presence of pre-event gut dysbiosis. Here, we applied broad range metabolomics to stools obtained 1-5 days before NEC developed from 9 cases (9 samples) and 19 (32 samples) controls matched for gestational age at birth and birth weight. The 764 identified metabolites identified six pathways that differ between cases and controls. We pursued sphingolipid metabolism because cases had decreased ceramides and increased sphingomyelins compared to controls, and because of the relevance of sphingolipids to human inflammatory disorders. Targeted analysis of samples from 23 cases and 46 controls confirmed the initial broad range observations. While metabolites provided only 73% accuracy of classification by machine learning, hierarchical clustering defined a sphingolipid associated grouping that contained 60% of the cases but only 13% of the controls, possibly identifying a pathophysiologically distinct subset of NEC. The clustering did not associate with any of the analyzed clinical and sample variables. We conclude that there are significant changes in sphingolipid metabolism components in pre-NEC stools compared to controls, but our data urge circumspection before using sphingolipids as broadly applicable predictive biomarkers.

Lanreotide in the management of small bowel angioectasias: seven-year data from a tertiary centre.

BACKGROUND AND AIMS: Haemorrhage from small bowel angioectasias (SBAs) can be debilitating to patients who are very often elderly and have multiple comorbidities. Our aim was to assess the use of lanreotide in addition to endotherapy in patients with SBAs. METHOD: Patients with SBAs on capsule endoscopy (CE) who received lanreotide injections from January 2010 to till the present day at the Royal Hallamshire Hospital in Sheffield were included. Baseline demographics were recorded. Efficacy was evaluated in terms of improvement in mean haemoglobin, transfusion requirements and bleeding episodes. RESULTS: Twelve patients (67% males, mean age 74 SD ± 15.5 years) were included. All patients had multiple comorbidities. Lanreotide was given at a dosage of 60 mg (42%), 90 mg (33%) or 120 mg (25%). It was given at a four-week interval in 75% of patients and at a six-week interval in 17% of patients. One patient (8%) received a single dose. The mean duration of treatment was 19 months SD ± 14.5. Only 17% of patients had their lanreotide stopped due to cholelithiasis. There was a significant improvement in mean haemoglobin: 86.8 versus 98.0 (131-166 g/L, p = .012). The mean number of bleeding episodes (4.18 versus 1.09, p = .010) and packed red cells (323 versus 152, p = .006) received improved. Patients required less DBEs ± APCs after starting lanreotide (19 versus 11 p = .048). CONCLUSION: Lanreotide is a useful adjuvant treatment to therapeutic enteroscopy in patients with refractory obscure gastrointestinal bleeding due to SBAs. It improves haemoglobin levels, reduces transfusion requirements, bleeding episodes and number of DBEs. Overall, it has a good safety profile.

A paper based graphene-nanocauliflower hybrid composite for point of care biosensing.

We demonstrate the first report of graphene paper functionalized with fractal platinum nanocauliflower for use in electrochemical biosensing of small molecules (glucose) or detection of pathogenic bacteria (Escherichia coli O157:H7). Raman spectroscopy, scanning electron microscopy and energy dispersive spectroscopy show that graphene oxide-coated nanocellulose was partially reduced by both thermal treatment, and further reduced by chemical treatment (ascorbic acid). Fractal nanoplatinum with cauliflower-like morphology was formed on the reduced graphene oxide paper using pulsed sonoelectrodeposition, producing a conductive paper with an extremely high electroactive surface area (0.29±0.13cm(2)), confirmed by cyclic voltammetry and electrochemical impedance spectroscopy. The platinum surface was functionalized with either glucose oxidase (via chitosan encapsulation) or a RNA aptamer (via covalent linking) for demonstration as a point of care biosensor. The detection limit for both glucose (0.08±0.02µM) and E. coli O157:H7 (≈4 CFUmL(-1)) were competitive with, or superior to, previously reported devices in the biosensing literature. The response time (6s for glucose and 12min for E. coli) were also similar to silicon biochip and commercial electrode sensors. The results demonstrate that the nanocellulose-graphene-nanoplatinum material is an excellent paper-based platform for development of electrochemical biosensors targeting small molecules or whole cells for use in point of care biosensing.

Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer.

BACKGROUND: The Panitumumab Randomized trial In combination with chemotherapy for Metastatic colorectal cancer to determine Efficacy (PRIME) demonstrated that panitumumab-FOLFOX4 significantly improved progression-free survival (PFS) versus FOLFOX4 as first-line treatment of wild-type (WT) KRAS metastatic colorectal cancer (mCRC), the primary end point of the study. PATIENTS AND METHODS: Patients were randomized 1:1 to panitumumab 6.0 mg/kg every 2 weeks + FOLFOX4 (arm 1) or FOLFOX4 (arm 2). This prespecified final descriptive analysis of efficacy and safety was planned for 30 months after the last patient was enrolled. RESULTS: A total of 1183 patients were randomized. Median PFS for WT KRAS mCRC was 10.0 months [95% confidence interval (CI) 9.3-11.4 months] for arm 1 and 8.6 months (95% CI 7.5-9.5 months) for arm 2; hazard ratio (HR) = 0.80; 95% CI 0.67-0.95; P = 0.01. Median overall survival (OS) for WT KRAS mCRC was 23.9 months (95% CI 20.3-27.7 months) for arm 1 and 19.7 months (95% CI 17.6-22.7 months) for arm 2; HR = 0.88; 95% CI 0.73-1.06; P = 0.17 (68% OS events). An exploratory analysis of updated survival (>80% OS events) was carried out which demonstrated improvement in OS; HR = 0.83; 95% CI 0.70-0.98; P = 0.03 for WT KRAS mCRC. The adverse event profile was consistent with the primary analysis. CONCLUSIONS: In WT KRAS mCRC, PFS was improved, objective response was higher, and there was a trend toward improved OS with panitumumab-FOLFOX4, with significant improvement in OS observed in an updated analysis of survival in patients with WT KRAS mCRC treated with panitumumab + FOLFOX4 versus FOLFOX4 alone (P = 0.03). These data support a positive benefit-risk profile for panitumumab-FOLFOX4 for patients with previously untreated WT KRAS mCRC. KRAS testing is critical to select appropriate patients for treatment with panitumumab.

Upper thermal tolerance of closely related Danio species.

The main finding of this study was that measuring maximum heart rate during incremental warming was an effective tool to estimate upper thermal limits in three small cyprinid Danio species, which differed significantly. Arrhenius breakpoint temperature for maximum heart rate, purportedly an index of optimum temperature, was 21·2 ± 0·4, 20·1 ± 0·4 and 18·9 ± 0·8° C (mean ± s.e.) for zebrafish Danio rerio, pearl danio Danio albolineatus and glowlight danio Danio choprae, respectively. The temperature where cardiac arrhythmias were first induced during warming (T(arr)) was 36·6 ± 0·7, 36·9 ± 0·8 and 33·2 ± 0·8° C (mean ± s.e.) and critical thermal maximum (T(Cm)) was 39·9 ± 0·1, 38·9 ± 0·1 and 37·2 ± 0·1° C (mean ± s.e.) for D. rerio, D. albolineatus and D. choprae, respectively. The finding that T(arr) was consistently 3-4° C lower than T(Cm) suggests that collapse of the cardiac life support system may be a critical trigger for upper temperature tolerance. The upper thermal limits established here, which correlate well with a broad natural environmental temperature range for D. rerio and a narrow one for D. choprae, suggest that upper thermal tolerance may be a genetic trait even among closely related species acclimated to common temperatures.

Final results from a randomized phase 3 study of FOLFIRI {+/-} panitumumab for second-line treatment of metastatic colorectal cancer.

BACKGROUND: The study 20050181 demonstrated significant improvements in progression-free survival (PFS), objective response, and a nonsignificant trend toward increased overall survival (OS) with panitumumab-FOLFIRI versus FOLFIRI alone for second-line wild-type (WT) KRAS metastatic colorectal cancer (mCRC). Updated long-term data from a prespecified descriptive analysis are reported. PATIENTS AND METHODS: Patients receiving one prior mCRC treatment were randomly assigned (1:1) to panitumumab (6.0 mg/kg)-FOLFIRI versus FOLFIRI every 2 weeks. Co-primary end points (PFS and OS) were prospectively analyzed by tumor KRAS status. RESULTS: One thousand one hundred and eighty-six patients were randomly assigned. In patients with WT KRAS tumors, panitumumab-FOLFIRI significantly improved PFS versus FOLFIRI [median 6.7 versus 4.9 months; hazard ratio (HR) 0.82 [95% confidence interval (CI) 0.69, 0.97]; P = 0.023]. A trend toward longer OS was observed (median 14.5 versus 12.5 months; HR 0.92 [95% CI 0.78, 1.10]; P = 0.37). Response rates improved from 10% to 36% (P < 0.0001). From post hoc analyses in patients receiving prior oxaliplatin-bevacizumab, panitumumab-FOLFIRI improved PFS (median 6.4 versus 3.7 months; HR 0.58 [95% CI 0.37, 0.90]; P = 0.014). PFS and OS appeared longer for worst-grade skin toxicity of 2-4, versus 0-1 or FOLFIRI. Safety results were as previously reported and consistent with the known toxicities with anti-epidermal growth factor receptor therapy. CONCLUSIONS: These data confirm the primary efficacy and safety findings of this trial and support panitumumab-FOLFIRI as a second-line treatment of WT KRAS mCRC.