Determining the gluonic gravitational form factors of the proton.

The proton is one of the main building blocks of all visible matter in the Universe1. Among its intrinsic properties are its electric charge, mass and spin2. These properties emerge from the complex dynamics of its fundamental constituents-quarks and gluons-described by the theory of quantum chromodynamics3-5. The electric charge and spin of protons, which are shared among the quarks, have been investigated previously using electron scattering2. An example is the highly precise measurement of the electric charge radius of the proton6. By contrast, little is known about the inner mass density of the proton, which is dominated by the energy carried by gluons. Gluons are hard to access using electron scattering because they do not carry an electromagnetic charge. Here we investigated the gravitational density of gluons using a small colour dipole, through the threshold photoproduction of the J/ψ particle. We determined the gluonic gravitational form factors of the proton7,8 from our measurement. We used a variety of models9-11 and determined, in all cases, a mass radius that is notably smaller than the electric charge radius. In some, but not all cases, depending on the model, the determined radius agrees well with first-principle predictions from lattice quantum chromodynamics12. This work paves the way for a deeper understanding of the salient role of gluons in providing gravitational mass to visible matter.

Glomerulonephritis With Positive Anti-Glomerular Basement Membrane Antibodies Following Alemtuzumab Treatment.

Presentation A 28 year old female presented to the emergency department with a one week history of headache, vomiting and diaphoresis. Creatinine on admission was 492 and urinalysis revealed blood and protein. This was 5 months after a second infusion of Alemtuzumab, for treatment of highly active relapsing remitting multiple sclerosis. Diagnosis Anti-glomerular basement membrane disease was diagnosed after a vasculitic screen was sent for suspected glomerulonephritis. Treatment Unfortunately despite early diagnosis and immunosuppressive treatment, the patient progressed to end stage kidney failure. Conclusion It is important to maintain a high index of suspicion and test for anti-GBM disease in patients receiving alemtuzumab who develop acute renal failure.

Epidemiological, clinical and genetic aspects of adult onset isolated focal dystonia in Ireland.

BACKGROUND: Adult onset idiopathic isolated focal dystonia presents with a number of phenotypes. Reported prevalence rates vary considerably; well-characterized cohorts are important to our understanding of this disorder. AIM: To perform a nationwide epidemiological study of adult onset idiopathic isolated focal dystonia in the Republic of Ireland. METHODS: Patients with adult onset idiopathic isolated focal dystonia were recruited from multiple sources. Diagnosis was based on assessment by a neurologist with an expertise in movement disorders. When consent was obtained, a number of clinical features including family history were assessed. RESULTS: On the prevalence date there were 592 individuals in Ireland with adult onset idiopathic isolated focal dystonia, a point prevalence of 17.8 per 100 000 (95% confidence interval 16.4-19.2). Phenotype numbers were cervical dystonia 410 (69.2%), blepharospasm 102 (17.2%), focal hand dystonia 39 (6.6%), spasmodic dysphonia 18 (3.0%), musician's dystonia 17 (2.9%) and oromandibular dystonia six (1.0%). Sixty-two (16.5%) of 375 consenting index cases had a relative with clinically confirmed adult onset idiopathic isolated focal dystonia (18 multiplex and 24 duplex families). Marked variations in the proportions of patients with tremor, segmental spread, sensory tricks, pain and psychiatric symptoms by phenotype were documented. CONCLUSIONS: The prevalence of adult onset idiopathic isolated focal dystonia in Ireland is higher than that recorded in many similar service-based epidemiological studies but is still likely to be an underestimate. The low proportion of individuals with blepharospasm may reflect reduced environmental exposure to sunlight in Ireland. This study will serve as a resource for international comparative studies of environmental and genetic factors in the pathogenesis of the disorder.

Myasthenia gravis: a population-based epidemiological study.

Myasthenia Gravis (MG) is a disorder affecting components of the neuromuscular junction. Epidemiological studies show rising incidence and prevalence rates. The aim of this study was to determine the incidence and prevalence of MG in the Republic of Ireland. Data sources included patient lists from consultant neurologists and ophthalmologists, a neuroimmunology laboratory, general practitioners and the Myasthenia Gravis Association. A total of 1715 cases were identified, of which 706 definite, probable or possible autoimmune and congenital MG cases were included. The overall prevalence rate from the data obtained is 15.38/100,000. The study demonstrated a female preponderance (female:male of 1.3: 1) and some geographical variation within Ireland. The average incidence rate for the years 2000 to 2009 was 11.3 per year; the rate for the current decade is 18 per year. The increasing number of diagnoses may be due to improved access to diagnostic investigations and increasing awareness of the clinical manifestations.

Paediatric estimated average glucose in children with Type 1 diabetes.

AIM: Estimated average glucose has been used to transform HbA1c into a glucose measure that might better inform patients of their glycaemic control. The data set used to obtain the estimated average glucose equation was derived in adults with Type 1 and Type 2 diabetes, along with normal healthy control subjects, and requires testing in children. METHODS: This was a cross-sectional study of 234 children and young people (106 male) with Type 1 diabetes aged 4.0-23.5 years who underwent continuous glucose monitoring over a 5-day period along with a measure of HbA1c . Regression analysis was used to determine estimated average glucose and agreement was assessed with the average glucose estimated from the Nathan equation: Nathan average glucose equation = 1.59 (HbA1c% ) - 2.59. RESULTS: Mean HbA1c was 76 mmol/mol (25.1) [9.1 (2.3)%] and mean continuous glucose monitoring tissue glucose was 10.4 (2.6) mmol/l. The relationship between continuous glucose monitoring tissue glucose and HbA1c was described by the paediatric equation: paediatric estimated average glucose = 0.49 (HbA1c %) + 5.95 (r = 0.45; P < 0.001). The mean paediatric estimated average glucose was 10.4 (1.1) mmol/l compared with that from the Nathan average glucose equation of 11.9 (3.7) mmol/l (P < 0.001). Overall, the paediatric estimated average glucose was 2.7 mmol/l lower than the Nathan estimated average glucose, with a 95% limit of agreement of ± 0.5 mmol/l. The agreement was very close with HbA1c values below 80 mmol/mol (9.5%). CONCLUSION: These data suggest that the Nathan estimated average glucose could be used in children and young people with Type 1 diabetes. Caution should still be exercised in the estimates derived for average glucose as the data set is skewed in both Nathan and paediatric average glucose estimates in opposite directions because of the differences in average HbA1c .

CCR5-Δ32 genotype does not improve predictive value of IL28B polymorphisms for treatment response in chronic HCV infection.

IL28B polymorphisms strongly predict spontaneous and treatment-induced clearance of hepatitis C virus (HCV) infection. A recent study proposed a 32-base pair deletion in the CC-chemokine receptor 5 (CCR5) gene (CCR5-Δ32) interacting with the IL28B polymorphisms to influence spontaneous HCV clearance. The aim of this study was to clarify the role of CCR5-Δ32 in treatment-induced clearance of chronic hepatitis C (CHC). A cross-sectional cohort of 813 Caucasian patients with CHC genotype 1 (365 responders and 448 non-responders) who had received standard of care dual therapy with interferon (IFN)-α and ribavirin (RBV) was genotyped for the CCR5-Δ32 and IL28B polymorphisms to examine their interaction with respect to treatment response. CCR5-Δ32 did not influence treatment-induced recovery to IFN-α/RBV in CHC, and did not improve prediction of sustained virological response in the context of the IL28B polymorphisms in a multivariate model. CCR5-Δ32 homozygotes were significantly more frequent in those with CHC than healthy controls in the European cohorts (2.9% vs 0.4%, P<0.0001), but not in Australians of European ancestry. In conclusion, CCR5-Δ32 does not influence treatment response in the context of IL28B polymorphisms. Although CCR5-Δ32 may affect viral clearance within closely controlled geographical and genetic environments, we found no effect in larger cohorts treated with dual therapy.

Variation in human genes encoding adhesion and proinflammatory molecules are associated with severe malaria in the Vietnamese.

The genetic basis for susceptibility to malaria has been studied widely in African populations but less is known of the contribution of specific genetic variants in Asian populations. We genotyped 67 single-nucleotide polymorphisms (SNPs) in 1030 severe malaria cases and 2840 controls from Vietnam. After data quality control, genotyping data of 956 cases and 2350 controls were analysed for 65 SNPs (3 gender confirmation, 62 positioned in/near 42 malarial candidate genes). A total of 14 SNPs were monomorphic and 2 (rs8078340 and rs33950507) were not in Hardy-Weinberg equilibrium in controls (P<0.01). In all, 7/46 SNPs in 6 genes (ICAM1, IL1A, IL17RC, IL13, LTA and TNF) were associated with severe malaria, with 3/7 SNPs in the TNF/LTA region. Genotype-phenotype correlations between SNPs and clinical parameters revealed that genotypes of rs708567 (IL17RC) correlate with parasitemia (P=0.028, r(2)=0.0086), with GG homozygotes having the lowest parasite burden. Additionally, rs708567 GG homozygotes had a decreased risk of severe malaria (P=0.007, OR=0.78 (95% CI; 0.65-0.93)) and death (P=0.028, OR=0.58 (95% CI; 0.37-0.93)) than those with AA and AG genotypes. In summary, variants in six genes encoding adhesion and proinflammatory molecules are associated with severe malaria in the Vietnamese. Further replicative studies in independent populations will be necessary to confirm these findings.

A web-based electronic neurology referral system: a solution for an overburdened healthcare system?

Ireland has the lowest number of consultant neurologists per capita in Europe. This results in long waiting lists, overbooked clinics, unnecessary emergency department presentations and patient frustration. In 2006, the neurology department in St. Vincent's University Hospital and the National Healthlink project, launched an internet referral system (Neurolink) for GPs, to alleviate the administrative burden on staff, reduce unnecessary visits for patients, shorten waiting lists and improve patient care. 710 electronic referrals from GPs between December 2006 and January 2011 were analysed. The average time taken to for a consultant to reply to a GP referral was 19hours 8minutes. When asked their opinion as to the suspected aetiology 33.7% (239/710) of GPs selected the option "unknown", followed by epilepsy 12.1% (86/710), migraine 12% (85/710), and multiple sclerosis 7.6% (54/710). Significantly, 19% (127/662) of referrals did not require a neurology outpatient appointment and the GP was given advice. The results highlight the benefits of using an electronic communication system with primary care; allowing prompt response to GP enquires, early initiation of treatment and reducing the number of patients attending hospital clinics.

Flavor decomposition of the elastic nucleon electromagnetic form factors.

The u- and d-quark contributions to the elastic nucleon electromagnetic form factors have been determined by using experimental data on G(E)(n), G(M)(n), G(E)(p), and G(M)(p). Such a flavor separation of the form factors became possible up to negative four-momentum transfer squared Q(2) = 3.4 GeV(2) with recent data on G(E)(n) from Hall A at Jefferson Lab. For Q(2) above 1 GeV(2), for both the u and the d quark, the ratio of the Pauli and Dirac form factors, F(2)/F(1), was found to be almost constant in sharp contrast to the behavior of F(2)/F(1) for the proton as a whole. Also, again for Q(2)>1 GeV(2), both F(2)(d) and F(1)(d) are roughly proportional to 1/Q(4), whereas the dropoff of F(2)(u) and F(1)(u) is more gradual.

Response to "isolated head tremor: A DAT SPECT and somatosensory temporal discrimination study."

In response to Ferrazano and colleagues' observation of normal DAT binding in patients with isolated head tremor but with abnormal STDT, we report normal 123-IBZM SPECT in a cohort of patients with adult-onset idiopathic focal dystonia with cervical dystonia and their unaffected first-degree relatives both with normal and abnormal TDTs. We discuss molecular imaging findings in dystonia.

Measurements of the electric form factor of the neutron up to Q2=3.4 GeV2 using the reaction 3He(e,e'n)pp.

The electric form factor of the neutron was determined from studies of the reaction 3He(e,e'n)pp in quasielastic kinematics in Hall A at Jefferson Lab. Longitudinally polarized electrons were scattered off a polarized target in which the nuclear polarization was oriented perpendicular to the momentum transfer. The scattered electrons were detected in a magnetic spectrometer in coincidence with neutrons that were registered in a large-solid-angle detector. More than doubling the Q2 range over which it is known, we find G(E)(n)=0.0236±0.0017(stat)±0.0026(syst), 0.0208±0.0024±0.0019, and 0.0147±0.0020±0.0014 for Q(2)=1.72, 2.48, and 3.41 GeV2, respectively.

Paediatric antimicrobial stewardship programmes in the UK's regional children's hospitals.

A survey was conducted in UK regional children's hospitals with paediatric intensive care and paediatric infectious disease (PID) departments to describe the characteristics of paediatric antimicrobial stewardship (PAS) programmes. A structured questionnaire was sent to PAS coordinators. 'Audit and feedback' was implemented in 13 out of 17 centres. Microbiology-led services were more likely to implement antimicrobial restriction (75% vs 33% in PID-led services), to focus on broad-spectrum antibiotics, and to review patients with positive blood cultures. PID-led services were more likely to identify patients from e-prescribing or drug charts and review all antimicrobials. A PAS network has been established.

Self-reported prescribing for hypertension in general practice.

OBJECTIVE: To describe the self-reported management of hypertension in general practice and how this compares to national guidelines for hypertension. DESIGN: Analysis of self-reported cross-sectional clinical audit data. SETTING: Australian general practice for the years 1999, 2001, 2003 and 2004. STUDY POPULATION: A total of 5247 general practitioners who voluntarily participated in one of four hypertension clinical audits and provided data for 105,086 adult patients with a previous diagnosis of hypertension. MAIN OUTCOME MEASURES: Selection of blood pressure targets consistent with recommendation of hypertension guidelines, percentage of patients achieving target blood pressure and percentage of patients with selected co-morbidities treated with the preferred class of antihypertensive medications. RESULTS: In 2001, target blood pressures of 140/90 mmHg and 130/85 mmHg were being used for 38% and 55% of patients, respectively. In 2004, target blood pressures were 140/90 mmHg (39%), 130/85 mmHg (49%) and 125/75 mmHg (0.5%). In 2003 and 2004, 58% and 70% of patients were reported to have achieved a target blood pressure that was consistent with guidelines according to patient age and co-morbidities. However, only 54-62% of hypertensive patients with heart failure were prescribed an ACE inhibitor and 52% of patients with a history of myocardial infarction were receiving a beta-blocker or ACE inhibitor. CONCLUSIONS: The self-reported data from general practitioners participating in clinical audits show that these general practitioners are using blood pressures targets consistent with guideline recommendations for most patients and that more patients are reaching their target blood pressure. However, drug selection based on co-morbidities could improve.

Hepatocyte transplantation: a review of laboratory techniques and clinical experiences.

Orthotopic liver transplantation (OLT) is standard clinical practice for patients with severe and end-stage chronic liver disease. However, the chronic shortage of donor livers and parallel growth of the transplant waiting list mean that a substantial proportion of patients die while waiting for a donor liver. Attempts to reduce the waiting list by use of split-liver and living-related live donor techniques have had some impact, but additional approaches to management are vital if the death rate is to be significantly reduced. Extensive laboratory research work and limited clinical trials have shown that hepatocyte transplantation may be useful in bridging some patients to OLT. A major limiting factor has been the shortage of mature functioning human hepatocytes, which are currently mostly obtained from livers rejected for OLT. This review examines potential hepatocyte sources, hepatocyte isolation methods and preservation protocols that have been successfully established, along with an overview of clinical results.

Neurosarcoidosis: clinical presentations and changing treatment patterns in an Irish Caucasian population.

BACKGROUND: The clinical manifestations of neurosarcoidosis are highly variable and it should be considered as a potential differential diagnosis in any neurological presentation. AIM: This study was designed to describe the clinical, diagnostic, and treatment patterns and functional outcome in a Caucasian neurosarcoidosis population. DESIGN: A retrospective analysis was performed on prospectively recorded data in patients attending our neurology clinic between 2008 and 2014 with a diagnosis of definite or probable neurosarcoidosis according to Zajiek criteria. METHODS: Detailed clinical features, baseline demographic data, results of investigations, treatment type and duration, and clinical outcomes were collated. RESULTS: Eleven patients were identified (55% men) with mean age 39 years (range 21-63). Four had a prior history of systemic sarcoidosis leading to earlier diagnosis (6.7 vs 13.1 months). Six were found to have evidence of systemic sarcoidosis on further investigation and one was biopsy proven isolated neurosarcoidosis. The commonest site of CNS involvement was the cranial nerves (64%), and headache (45%) was the most frequent presenting symptom. MRI abnormalities included leptomeningeal enhancement, white matter lesions, acute arteritis, spinal cord lesion, and cauda equina enhancement. The commonest CSF finding was raised protein (n = 6) and a lymphocytic pleocytosis (n = 7). Serum ACE was only elevated in three cases. Ten patients were treated with both corticosteroids and steroid-sparing agents 8 of whom went into remission. CONCLUSIONS: This series highlights the diverse nature of neurosarcoidosis. Early introduction of aggressive therapy with corticosteroids and steroid-sparing agents appears to improve clinical outcome.

Nurses experiences of working in Crisis Resolution Home Treatment Teams with its additional gatekeeping responsibilities.

INTRODUCTION: Through their gatekeeping role, CRHTT aim to reduce inappropriate admissions, facilitate early discharge from hospital and maximize the ability of service users to live independently within their own communities. It is evident that there is a vast array of literature on CRHTT internationally, however, little evidence on nurses experiences of working within CRHTT and gatekeeping. Therefore, in the light of limited research, this study aims to expand the current evidence base by exploring nurse's experiences of working in CRHTT with its additional gatekeeping responsibilities. METHODOLOGY: Six nurses working across two CRHTT's were interviewed using semi-structured interviews. Data were analysed through the use of thematic analysis. RESULTS: Four key themes emerged which were, 'CRHTT as a specialist role', 'core principles of the gatekeeping role', 'redefining risk management for gatekeepers in CRHTT' and 'the future of gatekeeping'. DISCUSSION: It is evident through nurse's experiences of working within CRHTT and gatekeeping that their roles were very dynamic and challenging. A positive risk-taking approach contributed towards the success of CRHTT as gatekeepers. Family members played a significant role in ensuring gatekeeping remained a priority consistent with Government targets. Clinical Implications and recommendations for future research are discussed.

Posterior reversible encephalopathy syndrome (PRES) associated with liquorice consumption.

IMPORTANCE: Posterior reversible encephalopathy syndrome (PRES) is a medical emergency but prompt recognition, early institution of supportive care and identifying and removing potential triggers are associated with a good clinical outcome. We report an unusual case of PRES associated with liquorice consumption. OBSERVATIONS: A 56-year-old lady presented with thunderclap headache, visual disturbance and a generalised tonic-clonic seizure. Blood pressure on admission was markedly elevated but improved within 24 h. Cranial CT and lumbar puncture were normal (no xanthochromia). She had hypokalaemia. Cranial MRI revealed abnormalities in the occipital lobes consistent with PRES. There was no evidence of restricted diffusion or vasoconstriction. Follow-up MRI 3 weeks later demonstrated complete resolution. On direct questioning she revealed in recent months she had habitually eaten liquorice sweets each day; they were "on special offer" in her local shop. CONCLUSION AND RELEVANCE: Liquorice contains a biologically active compound glycyrrhizic acid which inhibits 11ß hydroxysteroid dehydrogenase. Excessive liquorice consumption can cause mineralocorticoid excess and has been recently reported to cause PRES. We propose that in the absence of other triggers, frequent liquorice consumption precipitated the development of PRES in our patient and should be considered as a possible cause of this condition.

Review article: portal vein thrombosis -- new insights into aetiology and management.

Portal vein thrombosis may occur in the presence or absence of underlying liver disease, and a combination of local and systemic factors are increasingly recognized to be important in its development. Acute and chronic portal vein thrombosis have traditionally been considered separately, although a clear clinical distinction may be difficult. Gastrooesophageal varices are an important complication of portal vein thrombosis, but they follow a different natural history to those with portal hypertension related to cirrhosis. Consensus on optimal treatment continues to be hampered by a lack of randomized trials, but recent studies demonstrate the efficacy of thrombolytic therapy in acute thrombosis, and the apparent safety and benefit of anticoagulation in patients with chronic portal vein thrombosis.

Presenilin-1 mutation (E280G), spastic paraparesis, and cranial MRI white-matter abnormalities.

The authors report unusual presentations of members of an Irish family with familial AD due to an E280G mutation in exon 8 of presenilin-1. One had spastic paraparesis and white matter abnormalities on cranial MRI. A sibling had an internuclear ophthalmoplegia, spastic-ataxic quadriparesis, and "cotton-wool plaques" with amyloid angiopathy on brain biopsy. Another affected sibling also had MRI white matter abnormalities. The MRI findings may reflect an ischemic leukoencephalopathy due to amyloid angiopathy affecting meningocortical vessels.