Single-layer-coated beam splitters for the division-of-amplitude photopolarimeter

A design procedure is presented for a near-optimal, single-layer-coated prism beam splitter that serves as the key optical element of the division-of-amplitude photopolarimeter (DOAP). For given film and substrate refractive indices, the angle of incidence and film thickness are selected such that the ellipsometric differential phase shifts in reflection and transmission Delta_r and Delta_t differ by ±pi/2, and the normalized determinant of the instrument matrix is maximized. The best results are obtained by using high-index films on low-index substrates. This is illustrated by examples of ZnS and GaP films on silica prisms in the visible and Si, Ge, and PbTe films on Irtran 1 substrates in the infrared. A 16° Si-prism DOAP beam splitter at the 1.55-µm lightwave-communications wavelength is also presented. It uses a 163-nm SiO2 coating on the entrance face to satisfy the optimum delta condition at 73° incidence, and the determinant of the instrument matrix is 78.23% of its theoretical maximum. The exit face of the Si prism is antireflection coated with a 208-nm Si3N4 film

Single-layer-coated beam splitters for the division-of-amplitude photopolarimeter

A design procedure is presented for a near-optimal, single-layer-coated prism beam splitter that serves as the key optical element of the division-of-amplitude photopolarimeter (DOAP). For given film and substrate refractive indices, the angle of incidence and film thickness are selected such that the ellipsometric differential phase shifts in reflection and transmission Delta_r and Delta_t differ by ±pi/2, and the normalized determinant of the instrument matrix is maximized. The best results are obtained by using high-index films on low-index substrates. This is illustrated by examples of ZnS and GaP films on silica prisms in the visible and Si, Ge, and PbTe films on Irtran 1 substrates in the infrared. A 16° Si-prism DOAP beam splitter at the 1.55-µm lightwave-communications wavelength is also presented. It uses a 163-nm SiO2 coating on the entrance face to satisfy the optimum delta condition at 73° incidence, and the determinant of the instrument matrix is 78.23% of its theoretical maximum. The exit face of the Si prism is antireflection coated with a 208-nm Si3N4 film

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Gastric Cancer Pre-Stage Detection and Early Diagnosis of Gastritis Using Serum Protein Signatures

Background: A gastric cancer (GC) diagnosis relies on histopathology. Endoscopy rates are increasing. Helicobacter pylori infection is a major GC risk factor. In an effort to elucidate abundant blood biomarkers, and potentially reduce the number of diagnostic surgical interventions, we investigated sera and biopsies from a cohort of 219 H. pylori positive and negative patients diagnosed with GC, gastritis, and ulcers. This allowed the comparative investigation of the different gastroduodenal diseases, and the exclusion of protein changes resulting from bacterial infection or inflammation of the gastric mucosa when searching for GC-dependent proteins. Methods: High-definition mass spectrometry-based expression analysis of tryptically digested proteins was performed, followed by multivariate statistical and network analyses for the different disease groups, with respect to H. pylori infection status. Significantly regulated proteins differing more than two-fold between groups were shortlisted, and their role in gastritis and GC discussed. Results: We present data of comparative protein analyses of biopsies and sera from patients suffering from mild to advanced gastritis, ulcers, and early to advanced GC, in conjunction with a wealth of metadata, clinical information, histopathological evaluation, and H. pylori infection status. We used samples from pre-malignant stages to extract prospective serum markers for early-stage GC, and present a 29-protein marker panel containing, amongst others, integrin Beta-6 and glutathione peroxidase. Furthermore, ten serum markers specific for advanced GC, independent of H. pylori infection, are provided. They include CRP, protein S100A9, and kallistatin. The majority of these proteins were previously discussed in the context of cancer or GC. In addition, we detected hypoalbuminemia and increased fibrinogen serum levels in gastritis. Conclusion: Two protein panels were suggested for the development of multiplex tests for GC serum diagnostics. For most of the elements contained in these panels, individual commercial tests are available. Thus, we envision the design of multi-protein assays, incorporating several to all of the panel members, in order to gain a level of specificity that cannot be achieved by testing a single protein alone. As their development and validation will take time, gastritis diagnosis based on the fibrinogen to albumin serum ratio may be a quick way forward. Its determination at the primary/secondary care level for early diagnosis could significantly reduce the number of referrals to endoscopy. Preventive measures are in high demand. The protein marker panels presented in this work will contribute to improved GC diagnostics, once they have been transferred from a research result to a practical tool

Microbial Proteins in Stomach Biopsies Associated with Gastritis, Ulcer, and Gastric Cancer

(1) Background: Gastric cancer (GC) is the fourth leading cause of cancer-related deaths worldwide. Helicobacter pylori infection is a major risk factor, but other microbial species may also be involved. In the context of an earlier proteomics study of serum and biopsies of patients with gastroduodenal diseases, we explored here a simplified microbiome in these biopsies (H. pylori, Acinetobacter baumannii, Escherichia coli, Fusobacterium nucleatum, Bacteroides fragilis) on the protein level. (2) Methods: A cohort of 75 patients was divided into groups with respect to the findings of the normal gastric mucosa (NGM) and gastroduodenal disorders such as gastritis, ulcer, and gastric cancer (GC). The H. pylori infection status was determined. The protein expression analysis of the biopsy samples was carried out using high-definition mass spectrometry of the tryptic digest (label-free data-independent quantification and statistical analysis). (3) Results: The total of 304 bacterial protein matches were detected based on two or more peptide hits. Significantly regulated microbial proteins like virulence factor type IV secretion system protein CagE from H. pylori were found with more abundance in gastritis than in GC or NGM. This finding could reflect the increased microbial involvement in mucosa inflammation in line with current hypotheses. Abundant proteins across species were heat shock proteins and elongation factors. (4) Conclusions: Next to the bulk of human proteins, a number of species-specific bacterial proteins were detected in stomach biopsies of patients with gastroduodenal diseases, some of which, like those expressed by the cag pathogenicity island, may provide gateways to disease prevention without antibacterial intervention in order to reduce antibiotic resistance

Albumin aggregation and the re-solubilization of dried serum proteins

Albumin is known for its aggregation. As it is a major component of serum, it may be largely responsible for the difficulties in re-suspending dried serum proteins. We found it necessary to break up the solid pellet using a ball mill and subsequently a chaotropic agent and an organic solvent to generate a homogenous protein solution suitable for mass spectrometry-based protein expression analysis.Albumin ist bekannt für seine Aggregation. Da es eine Hauptkomponente von Serum darstellt, ist es wahrscheinlich hauptsächlich für die Schwierigkeiten bei der Resuspendierung getrockneter Serum-Proteine zuständig. Wir stellten fest, dass es notwendig war, zunächst das trockene Pellet mit einer Kugelmühle zu zerstören. Danach mussten Puffer mit Chaotrop und organischen Lösungsmittel zugefügt werden, um eine homogene Proteinlösung generieren, die für die Massenspektrometrie-basierte Expressionsanalyse geeignet war

Fungal Immunology: Mechanisms of Host Innate Immune Recognition and Evasion by Pathogenic Fungi

For a fungal pathogen to successfully infect, colonize and spread inside a susceptible host, it must have overcome the host immune responses. The early recognition of the fungal pathogen-associated molecular patterns (PAMPS) by the host’s pattern recognition receptors (PRRs) results in the establishment of anti-fungal immunity. Although, our immune system has evolved several processes to combat these pathogens both at the innate and adaptive immune levels. These organisms have developed various escape strategies to evade the recognition by the host\u27s innate immune components and thus interfering with host immune mechanisms. In this chapter, we will summarize the major PRRs involved in sensing fungal PAMPS and most importantly the fungal tactics to escape the host\u27s innate immune surveillance and protective mechanisms

Update on the eradication of 'Helicobacter pylori' infection in adult and pediatric patients from the northern region of Pakistan

'Helicobacter pylori' infection is associated with different gastric diseases, notably gastric cancer. The present study is aimed at comparing the effectiveness of various 'H. pylori' eradication regimens among adult and pediatric patients. A total of 3178 (396 children) patients were recruited. 'H. pylori' infection was diagnosed by nuclear stable isotopic 13C urea breath test (UBT) and positive patients were randomly allocated first-line eradication regimens. The second or third-line regimens were assigned to those who had failed first-line treatment. A negative UBT at least 4 weeks after the completion of treatment indicated a successful eradication of 'H. pylori'. Eradication rates (ER) by per-protocol (PP) and intention-to-treat (ITT) analysis were recorded. The overall prevalence of 'H. pylori' infection was 61.2% and slightly higher in males as compared to females. The modified concomitant therapy showed higher PP (77.8%) and ITT (72.7%) ER as first-line treatment. Among second-line therapies, PP/ITT ER of 63.6% / 55.3% were observed for quadruple therapy in adults. Standard triple therapy with probiotic and modified concomitant therapy as first-line and quadruple therapy as a second line thus is the choice for 'H. pylori' eradication in adult gastric disease patients. In pediatric patients, standard triple therapy was more effective as a first-line with about 68.8% ER.Eine 'Helicobacter pylori'-Infection ist mit verschiedenen gastrischen Krankheiten assoziiert, insbesondere Magenkrebs. Diese Studie vergleicht die Effizienz verschiedener 'H. pylori'-Ausrottungs-Methoden bei erwachsenen Patienten und Kindern. Insgesamt wurden 3178 (396 Kinder) Patienten rekrutiert. Eine 'H. pylori'-Infection wurde mittels 13C-Harnstoff-Atemtest (UBT) diagnostiziert, und positive Patienten wurden nach dem Zufallsprinzip verschiedenen "first-line" Behandlungsverfahren zugeordnet. "Second" oder "third-line"-Behandlungen erhielten diejenigen, bei denen die erste Behandlung nicht erfolgreich war. Ein negativer UBT mindestens 4 Wochen nach der Beendigung der Behandlung indizierte die erfolgreiche Vernichtung von 'H. pylori'. Ausrottungsraten (ER) durch "per-protocol (PP)" und "intention-to-treat (ITT)"-Analysen wurden erfasst. Mit 61.2% waren etwas mehr Männer als Frauen infiziert. Die "modified concomitant"-Therapie zeigte höhere PP (77.8%) und ITT (72.7%) ER als erste Behandlung. Bei den "second-line"-Therapien wurden PP/ITT ER von 63.6% / 55.3% für die "quadruple"-Therapie in Erwachsenen beobachtet. Die "standard triple"-Therapie mit Probiotic und die "modified concomitant"-Therapie als "first" und die "quadruple"-Therapie als "second-line" ist daher die Wahl für eine 'H. pylori'-Vernichtung in erwachsenen Patienten mit gastrischen Krankheiten. In Kindern war die "standard triple"-Therapie effizienter als "first-line"-Behandlung mit ~68.8% ER

Causal Assessment of Serum Urate Levels in Cardiometabolic Diseases Through a Mendelian Randomization Study

AbstractBackgroundAlthough epidemiological studies have reported positive associations between circulating urate levels and cardiometabolic diseases, causality remains uncertain.ObjectivesThrough a Mendelian randomization approach, we assessed whether serum urate levels are causally relevant in type 2 diabetes mellitus (T2DM), coronary heart disease (CHD), ischemic stroke, and heart failure (HF).MethodsThis study investigated 28 single nucleotide polymorphisms known to regulate serum urate levels in association with various vascular and nonvascular risk factors to assess pleiotropy. To limit genetic confounding, 14 single nucleotide polymorphisms exclusively associated with serum urate levels were used in a genetic risk score to assess associations with the following cardiometabolic diseases (cases/controls): T2DM (26,488/83,964), CHD (54,501/68,275), ischemic stroke (14,779/67,312), and HF (4,526/18,400). As a positive control, this study also investigated our genetic instrument in 3,151 gout cases and 68,350 controls.ResultsSerum urate levels, increased by 1 SD due to the genetic score, were not associated with T2DM, CHD, ischemic stroke, or HF. These results were in contrast with previous prospective studies that did observe increased risks of these 4 cardiometabolic diseases for an equivalent increase in circulating urate levels. However, a 1 SD increase in serum urate levels due to the genetic score was associated with increased risk of gout (odds ratio: 5.84; 95% confidence interval: 4.56 to 7.49), which was directionally consistent with previous observations.ConclusionsEvidence from this study does not support a causal role of circulating serum urate levels in T2DM, CHD, ischemic stroke, or HF. Decreasing serum urate levels may not translate into risk reductions for cardiometabolic conditions