Oesophageal hypersensitivity in patients with gastro-oesophageal reflux symptoms: Prevalence and novel treatments

Background Gastro oesophageal reflux disease (GORD) is a leading cause of morbidity and economic importance worldwide. It is currently defined by the Montreal definition as a condition, which develops when the reflux of gastric content causes troublesome symptoms or complications. This definition based on symptoms is all encompassing, and further classification is made based on macroscopic mucosal injury as seen on gastroscopy, increased distal oesophageal acid and non acid exposure, based on 24 hour pH and impedance pH testing, and reflux symptom association. Thus, GORD may be sub classified into the following conditions – erosive reflux disease (ERD), non erosive reflux disease (NERD), reflux hypersensitivity (RH), functional heartburn (FH) and functional chest pain (FCP). Treatment of GORD is with acid suppression therapy, anti reflux therapy and pain modulation. The pathophysiology of GORD is thought to occur in a spectrum, with varying contributions from direct mucosal injury to peripheral sensitization and central sensitization. Further efforts to phenotype GORD populations, investigate mechanisms of symptom evolution and treatments are driven by a significant proportion of patients who are refractory to currently available therapies. Aims The aim of this body of work was to phenotype patients with RH, the least studied subtype of GORD, to investigate the effect of ONO 8539, a novel antagonist to the Prostaglandin E 1 receptor thought to be involved in pain perception on acid induced oesophageal pain hypersensitivity in patients with NERD, to investigate the effect of transcutaneous vagal nerve stimulation (tVNS) on an oesophageal pain model in healthy volunteers, and to investigate the effect of slow deep breathing on oesophageal pain hypersensitivity in patients with NERD. Methods I investigated the above aims in a retrospective cohort study on patients referred to the gastro intestinal physiology unit of the Royal London Hospital for investigation of typical GORD symptoms, a double blind placebo controlled two period cross over study in patients with NERD, a single blind sham controlled two period cross over study in healthy volunteers and single blind sham controlled parallel study in patients with NERD respectively. The first study was done as a service evaluation exercise and the latter three studies had ethical approval from the National Research and Ethics Service (NRES), QMUL Ethics and NRES respectively. Results I demonstrated that phenotypic characteristics in patients with RH were distinct from NERD and FH/FCP. This was the largest cohort of RH patients evaluated, and this body of work will contribute to further research on mechanisms, pathophysiology and treatments in RH. In my second study, I was not able to demonstrate an anti nociceptive effect of ONO 8539 versus placebo on oesophageal pain hypersensitivity in patients with NERD. In my third study, I was able to demonstrate an increase in anti nociceptive parasympathetic tone, and an increase in pain tolerance threshold with tVNS compared to sham stimulation in an oesophageal pain hypersensitivity model in healthy volunteers. In my final study, I was able to demonstrate an increase in parasympathetic tone, but no improvement in lag time to pain perception with a slow deep breathing protocol compared to a sham breathing protocol in a Modified Bernstein test model of distal oesophageal acid infusion in patients with NERD. Conclusions This body of work improves upon current knowledge of the phenotypic characteristics of RH, adding further weight to the definition of RH as a distinct condition. tVNS and deep slow breathing were shown to increase parasympathetic tone in healthy volunteers and patients with NERD respectively. The anti nociceptive effect of raising parasympathetic tone was only demonstrated in the healthy volunteer model of oesophageal pain hypersensitivity. The performance of the MBT model used in the two patient studies was not as reliable as the healthy volunteer model, and a new oesophageal pain hypersensitivity model for patients with NERD was propose

KEPUASAN ORANG TUA AKAN PELAYANAN PENDIDIKAN DI SDIT IQRA 1 KOTA BENGKULU

Tujuan peneltian ini adalah untuk mendiskripsikan apa yang menjadi dasar penentuan biaya investasi dan biaya operasi di SDIT Iqra 1 Kota Bengkulu dan bagaimana kepuasan orang tua dengan pelayanan pendidikan. Metode yang digunakan dalam penelitian ini adalah diskriptif kualitatif dan kuantitatif (metode campuran). Subjek penelitian adalah orang tua dan kepala Sekolah. Pengumpulan data menggunakan teknik wawancara, observasi, dan angket. Teknis analisis data menggunakan teknik reduksi data, penyajian data, dan pengambilan kesimpulan. Hasil yang didapat dari penelitian ini adalah dasar penentuan biaya investasi dan biaya operasi adalah hasil dari musyawarah antara pihak sekolah, yayasan sekolah, komite sekolah, dan orang tua, dan orang tua puas dengan pelayanan pendidikan di SDIT Iqra 1 Kota Bengkulu. Faktor yang mempengaruhi kepuasan orant tua tersebut adalah proses belajar mengajar yang sesuai dengan visi misi sekolah, aktifnya komunikasi antara siswa dan guru, terjalinnya komunikasi yang berkelanjutan antara orang tua dan guru, pelayanan tata usaha sekolah yang baik, dan hasil lulusan yang sesuai dengan standar sekolah

On the use of higher order bias approximations for 2SLS and k -class estimators with non-normal disturbances and many instruments

The first and second moment approximations for the k-class of estimators were originally obtained in a general static simultaneous equation model under the assumption that the structural disturbances were i.i.d. and normally distributed. Later, higher-order bias approximations were obtained and were shown to be important especially in highly over identified cases. It is shown that the higher order bias approximation continues to be valid under symmetric, but not necessarily normal, disturbances with an arbitrary degree of kurtosis, but not when the disturbances are asymmetric. A modified higher-order approximation for the bias is then obtained which includes the case of asymmetric disturbances. The effect of asymmetry in the disturbances is explored in the context of a two equation model where it is shown that the bias of 2SLS may be substantially changed when the skewness factor increases. The use of the bias approximation is illustrated using empirical applications relating to the return to schooling, where a model with many instruments is employed, and to higher education wage premia

UJI AKTIVITAS ANTIDIABETES EKSTRAK KERING BIJI MAHONI TERSTANDAR (Swietenia mahagoni Jacq) PADA MENCIT YANG DIINDUKSI ALOKSAN

Diabetes merupakan salah satu penyakit yang menjadi permasalahan di dunia. Peningkatan jumlah penderita diabetes melitus terjadi dari tahun ketahun, sehingga perlu adanya upaya untuk mencegah ataupun mengobati penyakit diabetes melitus tersebut. Salah satu upaya yang dapat dilakukan untuk mengobati diabetes melitus adalah salah satunya dengan obat tradisional yang berasal dari alam. Pengunaan obat tradisional merupakan tradisi nenek moyang yang telah ada sejak zaman dulu. Sehingga dalam hal ini penggunaan obat tradisonal sudah menjadi kebiasaan atau tradisi masyarakat Indonesia itu sendiri. Literatur Etnobotani melaporkan sekitar 800 tanaman memiliki potensi antidiabetes dan lebih dari 1.200 spesies menunjukkan sebagai aktivitas antidiabetes. Organisasi Kesehatan Dunia (WHO) telah merekomendasikan untuk memanfaatkan tanaman tradisional untuk pengobatan diabetes (Kitukale and Chandewar, 2014). Salah satu tanaman Indonesia yang dapat di manfaatkan adalah biji mahoni (Swietenia mahagoni Jacq). Dari beberapa penelitian menunjukkkan hasil bahwa pada biji mahoni (Swietenia mahagoni Jacq) memiliki aktivitas sebagai antidiabetes. Pada biji mahoni terdapat kandungan kimia utama berupa senyawa golongan tetranortriterpenoid, swietenin yang memiliki efek hipoglikemik (Preedy et al, 2011)

The theory of international business: the role of economic models

This paper reviews the scope for economic modelling in international business studies. It argues for multi-level theory based on classic internalisation theory. It present a systems approach that encompasses both firm-level and industry-level analysis

On the origin of utility, weighting, and discounting functions: How they get their shapes and how to change their shapes

We present a theoretical account of the origin of the shapes of utility, probability weighting, and temporal discounting functions. In an experimental test of the theory, we systematically change the shape of revealed utility, weighting, and discounting functions by manipulating the distribution of monies, probabilities, and delays in the choices used to elicit them. The data demonstrate that there is no stable mapping between attribute values and their subjective equivalents. Expected and discounted utility theories, and also their descendants such as prospect theory and hyperbolic discounting theory, simply assert stable mappings to describe choice data and offer no account of the instability we find. We explain where the shape of the mapping comes from and, in describing the mechanism by which people choose, explain why the shape depends on the distribution of gains, losses, risks, and delays in the environment

The paralogues MAGOH and MAGOHB are oncogenic factors in high-grade gliomas and safeguard the splicing of cell division and cell cycle genes

The exon junction complex (EJC) plays key roles throughout the lifespan of RNA and is particularly relevant in the nervous system. We investigated the roles of two EJC members, the paralogs MAGOH and MAGOHB, with respect to brain tumour development. High MAGOH/MAGOHB expression was observed in 14 tumour types; glioblastoma (GBM) showed the greatest difference compared to normal tissue. Increased MAGOH/MAGOHB expression was associated with poor prognosis in glioma patients, while knockdown of MAGOH/MAGOHB affected different cancer phenotypes. Reduced MAGOH/MAGOHB expression in GBM cells caused alterations in the splicing profile, including re-splicing and skipping of multiple exons. The binding profiles of EJC proteins indicated that exons affected by MAGOH/MAGOHB knockdown accumulated fewer complexes on average, providing a possible explanation for their sensitivity to MAGOH/MAGOHB knockdown. Transcripts (genes) showing alterations in the splicing profile are mainly implicated in cell division, cell cycle, splicing, and translation. We propose that high MAGOH/MAGOHB levels are required to safeguard the splicing of genes in high demand in scenarios requiring increased cell proliferation (brain development and GBM growth), ensuring efficient cell division, cell cycle regulation, and gene expression (splicing and translation). Since differentiated neuronal cells do not require increased MAGOH/MAGOHB expression, targeting these paralogs is a potential option for treating GBM

First-Place Loving and Last-Place Loathing: How Rank in the Distribution of Performance Affects Effort Provision

Rank-order relative-performance evaluation, in which pay, promotion, symbolic awards, and educational achievement depend on the rank of individuals in the distribution of performance, is ubiquitous. Whenever organizations use rank-order relative-performance evaluation, people receive feedback about their rank. Using a real-effort experiment, we aim to discover whether people respond to the specific rank that they achieve. In particular, we leverage random variation in the allocation of rank among subjects who exerted the same effort to obtain a causal estimate of the rank response function that describes how effort provision responds to the content of rank-order feedback. We find that the rank response function is U-shaped. Subjects exhibit “first-place loving” and “last-place loathing”: that is, subjects work hardest after being ranked first or last. We discuss implications of our findings for the optimal design of performance feedback policies, workplace organizational structures, and incentives schemes

Active versus passive maintenance of visual nonverbal memory

Forgetting over the short-term has challenged researchers for more than a century, largely because of difficulty in controlling what goes on within the memory retention interval. But the “recent negative probes” procedure offers a valuable paradigm, by examining influences of (presumably) unattended memoranda from prior trials. Here we used a recent probes task to investigate forgetting for visual non-verbal short-term memory. Target stimuli (2 visually presented abstract shapes) on a trial were followed after a retention interval by a probe, and participants indicated whether the probe matched one of the target items. Proactive interference, and hence memory for old trial probes, was observed whereby participants were slowed in rejecting a non-matching probe on the present trial that nevertheless matched a target item on the previous trial (a recent negative probe). The attraction of the paradigm is that, by uncovering proactive influences of past trial probe stimuli, it is argued that active maintenance in memory of those probes is unlikely. In two experiments we recorded such proactive interference of prior trial items over a range of interstimulus (ISI) and intertrial (ITI) intervals (between 1 and 6 seconds respectively). Consistent with a proposed two-process memory conception (the active-passive memory model or APM), actively maintained memories on current trials decayed but passively “maintained,” or unattended, visual memories of stimuli on past trials did not