The locus of recognition memory signals in human cortex depends on the complexity of the memory representations.

According to a "Swiss Army Knife" model of the brain, cognitive functions such as episodic memory and face perception map onto distinct neural substrates. In contrast, representational accounts propose that each brain region is best explained not by which specialized function it performs, but by the type of information it represents with its neural firing. In a functional magnetic resonance imaging study, we asked whether the neural signals supporting recognition memory fall mandatorily within the medial temporal lobes (MTL), traditionally thought the seat of declarative memory, or whether these signals shift within cortex according to the content of the memory. Participants studied objects and scenes that were unique conjunctions of pre-defined visual features. Next, we tested recognition memory in a task that required mnemonic discrimination of both simple features and complex conjunctions. Feature memory signals were strongest in posterior visual regions, declining with anterior progression toward the MTL, while conjunction memory signals followed the opposite pattern. Moreover, feature memory signals correlated with feature memory discrimination performance most strongly in posterior visual regions, whereas conjunction memory signals correlated with conjunction memory discrimination most strongly in anterior sites. Thus, recognition memory signals shifted with changes in memory content, in line with representational accounts.

Baseline characteristics of children in the early glasses study.

PURPOSE: The relationship between refractive error at age 1 and the risk of developing amblyopia or accommodative esotropia, and the protection offered by early glasses, is unknown. These are determined in the Early Glasses Study, a prospective, population-based, longitudinal, randomized controlled study. We report baseline findings. METHODS: Healthy children aged 12-18 months were recruited at Children's Healthcare Centres (CHCs) and received an entry orthoptic examination followed by cycloplegic retinoscopy. Children with amblyopia, strabismus, ophthalmic disease or very high refractive error were excluded. Those exceeding the AAPOS 2003 Criteria (> + 3.5D spherical equivalent (SE), > 1.5D astigmatism, > 1.5D anisometropia) were randomized into wearing glasses or not, and are followed-up by research orthoptists. Other children are followed-up by regular vision screening at CHCs and visual acuity is measured in all children at age 4. RESULTS: Parents of 865 children were called, 123 were excluded. Of 742 children enrolled, 601 underwent the entry orthoptic examination at age 14.5 ± 1.7 months. Mean SE was + 1.73 ± 1.18D, astigmatism -0.70 ± 0.44D, anisometropia 0.21D (IQR: 0-0.25). Of 62 (10.3%) children exceeding the Criteria, 52 were randomized into wearing glasses or not. Of 539 other children, 522 are followed up at CHCs. In total, 31 were excluded: 2 had strabismus and amblyopia, 7 strabismus, 2 amblyopia suspect, 1 strabismus suspect, 1 squinting during sinusitis, 4 excessive refractive error, 9 myopia, 2 ptosis, 1 oculomotor apraxia, 1 Duane syndrome, 1 congenital nystagmus. CONCLUSION: Prevalence of strabismus (10/601) was as expected, but prevalence of amblyopia (2/601) was low, suggesting that common amblyopia develops later than generally thought. KEY MESSAGES: What is known • High refractive errors cause amblyopia, but no study has determined the exact relationship between the kind and size of refractive error at age 1 and the risk to develop amblyopia, and assessed the protective effect of glasses in a controlled, population-based, longitudinal study. What is new • At baseline, 601 children received a full orthoptic examination followed by retinoscopy in cycloplegia at the age of 14.5 ± 1.7 months; 10.3% had high refractive error exceeding spherical equivalent > + 3.5D, > 1.5D astigmatism, > 1D oblique astigmatism or > 1.5D anisometropia. • The prevalence of amblyopia was lower (0.3%) than expected, suggesting that most amblyopia develops after the first year of life. • The prevalence of anisometropia, associated with amblyopia in older children, was low (0.8%).

Comparison of solid-phase red cell adherence and microcolumn agglutination technology using untreated and enzyme-treated red blood cells.

Screening for clinically significant antibodies is crucial in transfusion medicine and is a routine part of pre-transfusion testing. The indirect antiglobulin test (IAT) is the most reliable and effective test for detecting clinically significant alloantibodies reacting at the antihuman globulin phase. Two of the main methods used for antibody detection and identification are solid-phase red cell adherence (SPRCA) and microcolumn agglutination technology (CAT), with or without enzyme-treated red blood cells (RBCs). This study was undertaken to detect and identify alloantibodies by performing antibody screen (ABS) and antibody identification (ABID) testing using SPRCA and CAT, with and without ficin-treated RBCs. Residual patient samples collected between 1 December 2020 and 19 May 2021 were saved, de-identified, and frozen at ≤-30°C before testing for alloantibodies. Seventy antibodies were detected in 53 samples among the 203 samples that underwent an ABS. Of those samples, 150 (73.0%) were nonreactive, 47 (23.1%) yielded positive results with both CAT and SPRCA, and six (3.0%) yielded positive ABS results with SPRCA only. Fifty-three samples that underwent ABID by both methods yielded eight samples with antibodies identified by SPRCA only. Additional enhancement of the CAT method by the use of ficin-treated RBCs was required to detect seven of the eight SPRCA-only antibodies; one sample remained nonreactive regardless. SPRCA testing detected clinically significant antibodies without the addition of enzyme-treated RBCs that was necessary in the CAT testing.

Diet and irritable bowel syndrome: an update from a UK consensus meeting.

There has been a renewed interest in the role of dietary therapies to manage irritable bowel syndrome (IBS), with diet high on the agenda for patients. Currently, interest has focussed on the use of traditional dietary advice (TDA), a gluten-free diet (GFD) and the low FODMAP diet (LFD). A consensus meeting was held to assess the role of these dietary therapies in IBS, in Sheffield, United Kingdom.Evidence for TDA is from case control studies and clinical experience. Randomised controlled trials (RCT) have demonstrated the benefit of soluble fibre in IBS. No studies have assessed TDA in comparison to a habitual or sham diet. There have been a number of RCTs demonstrating the efficacy of a GFD at short-term follow-up, with a lack of long-term outcomes. Whilst gluten may lead to symptom generation in IBS, other components of wheat may also play an important role, with recent interest in the role of fructans, wheat germ agglutinins, as well as alpha amylase trypsin inhibitors. There is good evidence for the use of a LFD at short-term follow-up, with emerging evidence demonstrating its efficacy at long-term follow-up. There is overlap between the LFD and GFD with IBS patients self-initiating gluten or wheat reduction as part of their LFD. Currently, there is a lack of evidence to suggest superiority of one diet over another, although TDA is more acceptable to patients.In view of this evidence, our consensus group recommends that dietary therapies for IBS should be offered by dietitians who first assess dietary triggers and then tailor the intervention according to patient choice. Given the lack of dietetic services, novel approaches such as employing group clinics and online webinars may maximise capacity and accessibility for patients. Further research is also required to assess the comparative efficacy of dietary therapies to other management strategies available to manage IBS.

Boosting confidence without boosting performance: item strength creates the illusion of source accuracy.

People often express high confidence for misremembered sources. Starns and Ksander ([2016]. Item strength influences source confidence and alters source memory zROC slopes. Journal of Experimental Psychology: Learning, Memory, and Cognition, 42(3), 351-365; hereafter SK16) found that this happens more often when a person is highly confident in memory for the item itself, and that simply increasing item memory can increase high-confidence source errors. Under the decision heuristic account, this pattern emerges because strong item memories contaminate source judgments by promoting high confidence responses even when source evidence is relatively weak. Consequently, strengthening item memory is predicted to increase confidence for both correct and incorrect source responses; however, SK16 could not assess this key prediction because their item-strength manipulation also impaired source memory. We report two experiments with new item-strengthening manipulations designed to minimise source memory impairments. Results replicated the evidence for the decision heuristic account reported by SK16 and provided additional support by showing a boost in source confidence for both correct and error responses when item memory was strengthened without accompanying source impairments .

Visual and semantic similarity norms for a photographic image stimulus set containing recognizable objects, animals and scenes.

We collected visual and semantic similarity norms for a set of photographic images comprising 120 recognizable objects/animals and 120 indoor/outdoor scenes. Human observers rated the similarity of pairs of images within four categories of stimuli-inanimate objects, animals, indoor scenes and outdoor scenes-via Amazon's Mechanical Turk. We performed multidimensional scaling (MDS) on the collected similarity ratings to visualize the perceived similarity for each image category, for both visual and semantic ratings. The MDS solutions revealed the expected similarity relationships between images within each category, along with intuitively sensible differences between visual and semantic similarity relationships for each category. Stress tests performed on the MDS solutions indicated that the MDS analyses captured meaningful levels of variance in the similarity data. These stimuli, associated norms and naming data are made available to all researchers, and should provide a useful resource for researchers of vision, memory and conceptual knowledge wishing to run experiments using well-parameterized stimulus sets.

Determinants of lung disease progression measured by lung clearance index in children with cystic fibrosis.

The lung clearance index (LCI) measured by the multiple breath washout (MBW) test is sensitive to early lung disease in children with cystic fibrosis. While LCI worsens during the preschool years in cystic fibrosis, there is limited evidence to clarify whether this continues during the early school age years, and whether the trajectory of disease progression as measured by LCI is modifiable.A cohort of children (healthy and cystic fibrosis) previously studied for 12 months as preschoolers were followed during school age (5-10 years). LCI was measured every 3 months for a period of 24 months using the Exhalyzer D MBW nitrogen washout device. Linear mixed effects regression was used to model changes in LCI over time.A total of 582 MBW measurements in 48 healthy subjects and 845 measurements in 64 cystic fibrosis subjects were available. The majority of children with cystic fibrosis had elevated LCI at the first preschool and first school age visits (57.8% (37 out of 64)), whereas all but six had normal forced expiratory volume in 1 s (FEV1) values at the first school age visit. During school age years, the course of disease was stable (-0.02 units·year-1 (95% CI -0.14-0.10). LCI measured during preschool years, as well as the rate of LCI change during this time period, were important determinants of LCI and FEV1, at school age.Preschool LCI was a major determinant of school age LCI; these findings further support that the preschool years are critical for early intervention strategies.

Reporting guideline for interventional trials of primary and incisional ventral hernia repair.

BACKGROUND: Primary and incisional ventral hernia trials collect unstandardized inconsistent data, limiting data interpretation and comparison. This study aimed to create two minimum data sets for primary and incisional ventral hernia interventional trials to standardize data collection and improve trial comparison. To support these data sets, standardized patient-reported outcome measures and trial methodology criteria were created. METHODS: To construct these data sets, nominal group technique methodology was employed, involving 15 internationally recognized abdominal wall surgeons and two patient representatives. Initially a maximum data set was created from previous systematic and panellist reviews. Thereafter, three stages of voting took place: stage 1, selection of the number of variables for data set inclusion; stage 2, selection of variables to be included; and stage 3, selection of variable definitions and detection methods. A steering committee interpreted and analysed the data. RESULTS: The maximum data set contained 245 variables. The three stages of voting commenced in October 2019 and had been completed by July 2020. The final primary ventral hernia data set included 32 variables, the incisional ventral hernia data set included 40 variables, the patient-reported outcome measures tool contained 25 questions, and 40 methodological criteria were chosen. The best known variable definitions were selected for accurate variable description. CT was selected as the optimal preoperative descriptor of hernia morphology. Standardized follow-up at 30 days, 1 year, and 5 years was selected. CONCLUSION: These minimum data sets, patient-reported outcome measures, and methodological criteria have allowed creation of a manual for investigators aiming to undertake primary ventral hernia or incisional ventral hernia interventional trials. Adopting these data sets will improve trial methods and comparisons.

Clinical Characteristics and Management of 50 Patients with Anti-GAD Ataxia: Gluten-Free Diet Has a Major Impact.

The objective of this study is to report the clinical characteristics and treatment of patients with progressive cerebellar ataxia associated with anti-GAD antibodies. We performed a retrospective review of all patients with anti-GAD ataxia managed at the Sheffield Ataxia Centre over the last 25 years. We identified 50 patients (62% females) with anti-GAD ataxia. The prevalence was 2.5% amongst 2000 patients with progressive ataxia of various causes. Mean age at onset was 55 and mean duration 8 years. Gaze-evoked nystagmus was present in 26%, cerebellar dysarthria in 26%, limb ataxia in 44% and gait ataxia in 100%. Nine patients (18%) had severe, 12 (24%) moderate and 29 (58%) mild ataxia. Ninety percent of patients had a history of additional autoimmune diseases. Family history of autoimmune diseases was seen in 52%. Baseline MR spectroscopy of the vermis was abnormal at presentation in 72%. Thirty-five patients (70%) had serological evidence of gluten sensitivity. All 35 went on gluten-free diet (GFD). Eighteen (51%) improved, 13 (37%) stabilised, 3 have started the GFD too recently to draw conclusions and one deteriorated. Mycophenolate was used in 16 patients, 7 (44%) improved, 2 stabilised, 6 have started the medication too recently to draw conclusions and one did not tolerate the drug. There is considerable overlap between anti-GAD ataxia and gluten ataxia. For those patients with both, strict GFD alone can be an effective treatment. Patients with anti-GAD ataxia and no gluten sensitivity respond well to immunosuppression.

Coeliac disease and noncoeliac wheat or gluten sensitivity.

Coeliac disease (CD) and noncoeliac wheat or gluten sensitivity (NCWS/NCGS) are common gluten-related disorders. Both conditions can present with gastrointestinal and extraintestinal manifestations, which can be a challenge for physicians to discern between. Whilst coeliac serology and histological assessment are required for the diagnosis of CD, there are no clear biomarkers for the diagnosis of NCGS. The management of both conditions is with a gluten-free diet (GFD), although the duration, as well as strictness of adherence to a GFD in NCGS, is unclear. Adherence to a GFD in CD can also be challenging, with recent developments of noninvasive assessments, although histological assessment via duodenal biopsies remains the gold standard. The management of refractory coeliac disease remains particularly challenging, often requiring specialist input. Whilst wheat is noted to be a trigger for symptom generation in NCGS, it is unclear which components of wheat are responsible for symptom generation in this group, with further research required to elucidate the pathophysiology.

International classification of abdominal wall planes (ICAP) to describe mesh insertion for ventral hernia repair.

BACKGROUND: Nomenclature for mesh insertion during ventral hernia repair is inconsistent and confusing. Several terms, including 'inlay', 'sublay' and 'underlay', can refer to the same anatomical planes in the indexed literature. This frustrates comparisons of surgical practice and may invalidate meta-analyses comparing surgical outcomes. The aim of this study was to establish an international classification of abdominal wall planes. METHODS: A Delphi study was conducted involving 20 internationally recognized abdominal wall surgeons. Different terms describing anterior abdominal wall planes were identified via literature review and expert consensus. The initial list comprised 59 possible terms. Panellists completed a questionnaire that suggested a list of options for individual abdominal wall planes. Consensus on a term was predefined as occurring if selected by at least 80 per cent of panellists. Terms scoring less than 20 per cent were removed. RESULTS: Voting started August 2018 and was completed by January 2019. In round 1, 43 terms (73 per cent) were selected by less than 20 per cent of panellists and 37 new terms were suggested, leaving 53 terms for round 2. Four planes reached consensus in round 2, with the terms 'onlay', 'inlay', 'preperitoneal' and 'intraperitoneal'. Thirty-five terms (66 per cent) were selected by less than 20 per cent of panellists and were removed. After round 3, consensus was achieved for 'anterectus', 'interoblique', 'retro-oblique' and 'retromuscular'. Default consensus was achieved for the 'retrorectus' and 'transversalis fascial' planes. CONCLUSION: Consensus concerning abdominal wall planes was agreed by 20 internationally recognized surgeons. Adoption should improve communication and comparison among surgeons and research studies.

ANTECEDENTES: La nomenclatura de la inserción de una malla para la reparación de una hernia incisional ventral (ventral hernia, VH) es inconsistente y confusa. En la literatura indexada se usan varios términos, tales como 'inlay', 'sublay', y 'underlay' que pueden referirse a los mismos planos anatómicos. Este hecho frustra las comparaciones de técnicas quirúrgicas e invalida los metaanálisis que comparan resultados quirúrgicos en función del plano de inserción de la malla. En consecuencia, el objetivo de este estudio fue establecer una clasificación internacional de los planos de la pared abdominal (International Classification of Abdominal Wall Planes, ICAP). MÉTODOS: Se realizó un estudio Delphi, en el que participaron 20 cirujanos de pared abdominal reconocidos internacionalmente. Se identificaron diferentes términos que describían los planos de la pared abdominal anterior mediante la revisión de la literatura y el consenso de expertos. La lista inicial incluía 59 términos posibles. Los panelistas completaron un cuestionario que sugería una lista de opciones para los planos individuales de la pared abdominal. El consenso sobre un término fue predefinido cuando dicho término había sido seleccionado por ≥ 80% de panelistas. Se eliminaron los términos con una puntuación < 20%. RESULTADOS: La votación comenzó en agosto de 2018 y se completó en enero de 2019. Durante la Ronda 1, 43 (73%) términos fueron seleccionados por < 20% de los panelistas y se sugirieron 37 términos nuevos, dejando 53 términos para la Ronda 2. Cuatro planos alcanzaron un consenso en la Ronda 2 con los términos 'onlay', 'inlay', 'pre-peritoneal' e 'intra-peritoneal'. Treinta y cinco (66%) términos fueron seleccionados por < 20% de los panelistas y fueron eliminados. Después de la Ronda 3, se logró un consenso para 'anterectus' (ante-recto), 'interoblique' (inter-oblicuo), 'retrooblique' (retro-oblicuo) y 'retromuscular'. Se alcanzó un consenso por defecto para los planos 'retrorectus' (retro-recto) y 'transversalis fascial' (fascial transverso). CONCLUSIÓN: La ICAP ha sido desarrollada por el consenso de 20 cirujanos reconocidos internacionalmente. Su implementación debería mejorar la comunicación y la comparación entre cirujanos y estudios de investigación.

The role of diet in irritable bowel syndrome: implications for dietary advice.

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder that affects approximately 10% of the population. Diet triggers symptoms in the vast majority of individuals with IBS. In view of this, there has been a focus on the role of diet in IBS. The diets currently being headlined for IBS include (i) traditional dietary advice, (ii) the low fermentable oligo-, di-, mono- saccharides and polyols (FODMAPs) diet and (iii) the gluten-free diet (GFD). Although traditional dietary advice is considered as the first-line dietary therapy, its evidence base is variable, with a few randomized controlled trials (RCTs) exploring the efficacy of this approach, other than for fibre. There are now a growing number of RCTs demonstrating the efficacy of the low FODMAP diet in the short-term, with some emerging data on the long-term 'adapted' low FODMAP diet. There are also several RCTs showing the benefits of a GFD in IBS; however, this concept is hampered with uncertainty as to the mechanism of action. Nevertheless, all of these dietary therapies are viable options for individuals with IBS, with the dietitian and patient engagement at the forefront of achieving success. However, future pragmatic studies are needed to clarify the comparative efficacy and convenience of implementing these various diets into routine life. Moreover, it is imperative to better delineate the concern that restrictive diets - such as the low FODMAP and GFD - may promote nutritional inadequacies, disordered eating behaviours, and lead to detrimental alterations to the gut microbiota.

Persistent mucosal damage and risk of epilepsy in people with celiac disease.

BACKGROUND AND PURPOSE: Celiac disease (CD) is associated with an increased risk of developing epilepsy, a risk that persists after CD diagnosis. A significant proportion of patients with CD have persistent villous atrophy (VA) on follow-up biopsy. The objective of this study was to determine whether persistent VA on follow-up biopsy affected long-term epilepsy risk and epilepsy-related hospital emergency admissions. METHODS: This was a nationwide cohort study. We identified all people in Sweden with histological evidence of CD who underwent a follow-up small intestinal biopsy (1969-2008). We compared those with persistent VA with those who showed histological improvement, assessing the development of epilepsy and related emergency hospital admissions (defined according to relevant International Classification of Diseases codes in the Swedish Patient Register). Cox regression analysis was used to assess outcome measures. RESULTS: Villous atrophy was present in 43% of 7590 people with CD who had a follow-up biopsy. The presence of persistent VA was significantly associated with a reduced risk of developing newly-diagnosed epilepsy (hazard ratio, 0.61; 95% confidence interval, 0.38-0.98). On stratified analysis, this effect was primarily amongst males (hazard ratio, 0.35; 95% confidence interval, 0.15-0.80). Among the 58 patients with CD with a prior diagnosis of epilepsy, those with persistent VA were less likely to visit an emergency department with epilepsy (hazard ratio, 0.37; 95% confidence interval, 0.09-1.09). CONCLUSIONS: In a population-based study of individuals with CD, persisting VA on follow-up biopsy was associated with reduced future risk of developing epilepsy but did not influence emergency epilepsy-related hospital admissions. The mechanism as to why persistent VA confers this benefit requires further exploration.

CD34 and BerEP4 Are Helpful to Distinguish Basaloid Tricholemmoma From Basal Cell Carcinoma.

Tricholemmoma, a benign follicular neoplasm with outer root sheath differentiation, typically comprises clear or pale cells, and when multiple is pathognomic of Cowden's syndrome. The tumor is probably underrecognized and in basaloid examples can be difficult to distinguish from basal cell carcinoma (BCC). We studied 55 tricholemmomas (including 15 basaloid cases) and compared immunohistochemical profile with nodular BCC from our archives. Basaloid and non-basaloid tricholemmomas had similar staining characteristics. BerEP4 was focally positive (range 10%-20%) in only 3/39 (7.7%) tricholemmomas compared with widespread positivity in BCC (90.8%, 139 of 151 cases with ≥50% tumor area stained). CD34 was expressed, usually focally (median 20%, range 10%-90%), in 52/53 (98.1%) tricholemmomas and was negative in all 21 BCCs stained. EMA staining lacked sensitivity or specificity in differentiating tricholemmoma from BCC. Five or more Merkel cells were found in 7/17 (40.1%) tricholemmomas and 1/23 (4.3%) nodular BCCs studied. In summary, immunohistochemistry is helpful in distinction between tricholemmoma, including difficult basaloid examples (BerEP4 negative or focal, CD34 positive) compared with BCC (BerEP4 widespread in most cases, CD34 negative). The presence of 5 or more Merkel cells is a relatively specific but not a particularly sensitive discriminator.

Assessment of daily activity patterns and biomarkers of pain, inflammation, and stress in lactating dairy cows diagnosed with clinical metritis.

The objectives of the present case-control study were to assess (1) daily activity patterns (lying time, number of steps, number of lying bouts, and lying bout duration), and (2) circulating concentrations of biomarkers of pain (substance P), inflammation (haptoglobin), and stress (cortisol) in lactating dairy cows diagnosed with clinical metritis. Lactating dairy cows (n = 200) from 2 commercial dairy herds were enrolled in the present study. Cows diagnosed with clinical metritis (n = 100) at 7 ± 3 d in milk were matched according to lactation and days in milk to cows without clinical metritis (NO-CM; n = 100). On study d 1, clinical metritis was diagnosed (using a Metricheck device, Simcro Tech Ltd., Hamilton, New Zealand) by the presence of watery, reddish, or brownish foul-smelling vaginal discharge, and blood samples were collected for assessment of circulating concentration of substance P, haptoglobin, cortisol, total calcium, ß-hydroxybutyrate, and blood cells. In addition, on study d 1 body condition of cows was visually assessed, and activity monitors were placed on the hind leg of a subset of cows (CM, n = 56; CON, n = 56) and were kept until study d 7. Cows showing any other signs of other diseases were not included in the study. Cows with clinical metritis tended to spend more time lying (CM = 628.92 min/d; NO-CM = 591.23 min/d) compared with NO-CM cows. Activity analysis by parity revealed that primiparous cows with clinical metritis spent more time lying compared with primiparous cows without clinical metritis. However, no differences in daily lying time were observed between multiparous cows with and without clinical metritis. Furthermore, cows in the CM group had a higher circulating concentration of substance P (CM = 47.15 pg/mL; NO-CM = 37.73 pg/mL) and haptoglobin (CM = 233.00 µg/mL; NO-CM = 99.98 µg/mL) when compared with NO-CM cows. Cows with clinical metritis had lower body condition score, and a greater proportion of cows in this group had hypocalcemia when compared with cows without clinical metritis. The circulating concentration of leukocytes and erythrocytes were decreased in cows with clinical metritis compared with cows without clinical metritis. Results from this study showed that concentrations of markers of inflammation, stress, pain, and activity were affected in cows diagnosed with clinical metritis; thus, strategies aimed to minimize the negative effects associated with clinical metritis may be required to improve the welfare of dairy cows.

Challenging diagnostic issues in adenomatous polyps with epithelial misplacement in bowel cancer screening: 5 years' experience of the Bowel Cancer Screening Programme Expert Board.

The diagnostic difficulties of differentiating epithelial misplacement from invasive cancer in colorectal adenomatous polyps have been recognised for many years. Nevertheless, the introduction of population screening in the UK has resulted in extraordinary diagnostic problems. Larger sigmoid colonic adenomatous polyps, which are those most likely to show epithelial misplacement, are specifically selected into such screening programmes, because these polyps are likely to bleed and screening is based on the detection of occult blood. The diagnostic challenges associated with this particular phenomenon have necessitated the institution of an 'Expert Board': this is a review of the first five years of its practice, during which time 256 polyps from 249 patients have been assessed. Indeed, the Expert Board contains three pathologists, because those pathologists do not necessarily agree, and a consensus diagnosis is required to drive appropriate patient management. However, this study has shown substantial levels of agreement between the three Expert Board pathologists, whereby the ultimate diagnosis has been changed, from that of the original referral diagnosis, by the Expert Board for half of all the polyps, in the substantial majority from malignant to benign. In 3% of polyp cases, the Expert Board consensus has been the dual diagnosis of both epithelial misplacement and adenocarcinoma, further illustrating the diagnostic difficulties. The Expert Board of the Bowel Cancer Screening Programme in the UK represents a unique and successful development in response to an extraordinary diagnostic conundrum created by the particular characteristics of bowel cancer screening.

Causes of progressive cerebellar ataxia: prospective evaluation of 1500 patients.

BACKGROUND: Cerebellar ataxias are the result of diverse disease processes that can be genetic or acquired. Establishing a diagnosis requires a methodical approach with expert clinical evaluation and investigations. We describe the causes of ataxia in 1500 patients with cerebellar ataxia. METHODS: All patients were referred to the Sheffield Ataxia Centre, UK, and underwent extensive investigations, including, where appropriate genetic testing using next-generation sequencing (NGS). Patients were followed up on a 6-monthly basis for reassessment and further investigations if indicated. RESULTS: A total of 1500 patients were assessed over 20 years. Twenty per cent had a family history, the remaining having sporadic ataxia. The commonest cause of sporadic ataxia was gluten ataxia (25%). A genetic cause was identified in 156 (13%) of sporadic cases with other causes being alcohol excess (12%) and cerebellar variant of multiple system atrophy (11%). Using NGS, positive results were obtained in 32% of 146 patients tested. The commonest ataxia identified was EA2. A genetic diagnosis was achieved in 57% of all familial ataxias. The commonest genetic ataxias were Friedreich's ataxia (22%), SCA6 (14%), EA2 (13%), SPG7 (10%) and mitochondrial disease (10%). The diagnostic yield following attendance at the Sheffield Ataxia Centre was 63%. CONCLUSIONS: Immune-mediated ataxias are common. Advances in genetic testing have significantly improved the diagnostic yield of patients suspected of having a genetic ataxia. Making a diagnosis of the cause of ataxia is essential due to potential therapeutic interventions for immune and some genetic ataxias.

Outcomes of a pediatric surgical oncology fellowship in a pediatric cancer institution.

Surgery plays an important role as part of the treatment plan in most children with malignant solid tumors in regards to initial biopsy, upfront resection, and delayed resection. Surgeons also play a critical role in the treatment of surgical complications that may arise during medical treatment. The pediatric surgical oncologist should be familiar with the current treatment guidelines, histology implications, chemotherapy and radiation side effects, tumor staging, and overall care of the child with cancer. Specific training in pediatric surgical oncology is not widespread internationally and it represents a potential undervalued intervention for improving global pediatric cancer care.

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.

Uncertainty of measurement in andrology: UK best practice guideline from the Association of Biomedical Andrologists.

Uncertainty of measurement has become a paramount factor to consider in pathology. In the UK, consideration of uncertainty of measurement is mandatory for medical laboratories who apply to be accredited against ISO15189:2012 via the United Kingdom Accreditation Service. This guideline intends to help those working within diagnostic andrology to better understand the concept of uncertainty, and how it can be applied to semen analysis and post-vasectomy semen analysis. The various areas where uncertainty may exist are identified, and guidance is provided to minimise this uncertainty. This guidance is produced by the Association of Biomedical Andrologists alongside experts in the field of andrology, in order to aid laboratory scientists in understanding and undertaking important tasks that will improve quality of their service.