Risk factors for complications after emergency surgery for paediatric appendicitis: a national prospective observational cohort study.

Appendicectomy is a common procedure in children with a low risk of mortality, however, complication rates and risk factors are largely unknown. This study aimed to characterise the incidence and epidemiology of postoperative complications in children undergoing appendicectomy in the UK. This multicentre prospective observational cohort study, which included children aged 1-16 y who underwent surgery for suspected appendicitis, was conducted between November 2019 and January 2022. The primary outcome was 30-day postoperative morbidity. Data collected included: patient characteristics; comorbidities; and physiological status. Multivariable regression analysis was used to identify independent risk factors for poor outcomes. Data from 2799 children recruited from 80 hospitals were analysed, of which 185 (7%) developed postoperative complications. Children from black and 'other' minority ethnic groups were at significantly higher risk of poor outcomes: OR (95%CI) 4.13 (1.87-9.08), p < 0.001 and 2.08 (1.12-3.87), p = 0.021, respectively. This finding was independent of socio-economic status and type of appendicitis found on histology. Other risk factors for complications included: ASA physical status ≥ 3 (OR (95%CI) 4.05 (1.70-9.67), p = 0.002); raised C-reactive protein (OR 95%CI 1.01 (1.00-1.01), p < 0.001); pyrexia (OR (95%CI) 1.77(1.20-2.63), p = 0.004); and peri-operative oxygen supplementation (OR (95%CI) 4.20 (1.44-12.24), p = 0.009). In the UK NHS, which is a universally accessible healthcare system, ethnicity, but not socio-economic status, was associated with an increased risk of postoperative complications in children having surgery for acute appendicitis. Further evaluations and interventions are required to address this health inequality in keeping with NHS and international priorities.

Building a Community Partnership for the Development of Health Ministries Within the African American Community: The Triad Pastors Network.

African Americans continue to have worse health outcomes despite attempts to reduce health disparities. This is due, in part, to inadequate access to healthcare, but also to the health care and medical mistrust experienced by communities of color. Churches and worship centers have historically served as cultural centers of trusted resources for educational, financial, and health information within African American communities and a growing number of collaborations have developed between academic institutions and community/faith entities. Herein, we describe the infrastructure of a true and sustainable partnership developed with > 100 prominent faith leaders within the Piedmont Triad region of North Carolina for the purpose of developing or expanding existing health ministries within houses of worship, to improve health literacy and overall health long-term. The Triad Pastors Network is an asset-based partnership between the Maya Angelou Center for Health Equity at Wake Forest University School of Medicine and faith leaders in the Piedmont Triad region of North Carolina that was created under the guiding principles of community engagement to improve health equity and decrease health disparities experienced by African American communities. A partnership in which co-equality and shared governance are the core of the framework provides an effective means of achieving health-related goals in a productive and efficient manner. Faith-based partnerships are reliable approaches for improving the health literacy needed to address health disparities and inequities in communities of color.

Registry-derived stage (RD-Stage) for capturing cancer stage at diagnosis for endometrial cancer.

BACKGROUND: Capture of cancer stage at diagnosis is important yet poorly reported by health services to population-based cancer registries. In this paper we describe current completeness of stage information for endometrial cancer available in Australian cancer registries; and develop and validate a set of rules to enable cancer registry medical coders to calculate stage using data available to them (registry-derived stage or 'RD-Stage'). METHODOLOGY: Rules for deriving RD-stage (Endometrial carcinoma) were developed using the American Joint Commission on Cancer (AJCC) TNM (tumour, nodes, metastasis) Staging System (8th Edition). An expert working group comprising cancer specialists responsible for delivering cancer care, epidemiologists and medical coders reviewed and endorsed the rules. Baseline completeness of data fields required to calculate RD-Stage, and calculation of the proportion of cases for whom an RD stage could be assigned, was assessed across each Australian jurisdiction. RD-Stage (Endometrial cancer) was calculated by Victorian Cancer Registry (VCR) medical coders and compared with clinical stage recorded by the patient's treating clinician and captured in the National Gynae-Oncology Registry (NGOR). RESULTS: The necessary data completeness level for calculating RD-Stage (Endometrial carcinoma) across various Australian jurisdictions varied from 0 to 89%. Three jurisdictions captured degree of spread of cancer, rendering RD-Stage unable to be calculated. RD-Stage (Endometrial carcinoma) could not be derived for 64/485 (13%) cases and was not captured for 44/485 (9%) cases in NGOR. At stage category level (I, II, III, IV), there was concordance between RD-Stage and NGOR captured stage in 393/410 (96%) of cases (95.8%, Kendall's coefficient = 0.95). CONCLUSION: A lack of consistency in data captured by, and data sources reporting to, population-based cancer registries meant that it was not possible to provide national endometrial carcinoma stage data at diagnosis. In a sample of Victorian cases, where surgical pathology was available, there was very good concordance between RD-Stage (Endometrial carcinoma) and clinician-recorded stage data available from NGOR. RD-Stage offers promise in capturing endometrial cancer stage at diagnosis for population epidemiological purposes when it is not provided by health services, but requires more extensive validation.

Prediction of obstructive sleep apnoea in children and adolescents with Down syndrome.

BACKGROUND: Obstructive sleep apnoea (OSA) is common in children and adolescents with Down syndrome (DS). Clinical guidelines recommend that all children with DS have polysomnography (PSG) for assessment of OSA by the age of 4 years, but access is limited and testing may be burdensome for children and families. METHODS: The purpose of this prospective cross-sectional cohort study was to identify a model to predict OSA in this group that could be tested in an external population to triage children and adolescents with DS for PSG. These models were based on a comprehensive set of potential predictive demographic, anthropometric, quality of life and sleep-related variables. RESULTS: The results of this study show the predictive power of a model based on the sleep disordered breathing subscale of the Pediatric Sleep Survey Instrument and sleep fragmentation quantified using actigraphy in determining moderate-severe OSA in children and adolescents with DS. This model exhibits high sensitivity (82%), specificity (80%), positive predictive value (75%) and negative predictive value (86%). CONCLUSIONS: We demonstrate the utility of a tool containing the sleep disordered breathing subscale of the Pediatric Sleep Survey Instrument and sleep fragmentation quantified using actigraphy in identifying children and adolescents with DS who have moderate/severe OSA.

Inflammatory breast cancer defined: proposed common diagnostic criteria to guide treatment and research.

PURPOSE: Inflammatory breast cancer is a deadly and aggressive type of breast cancer. A key challenge relates to the need for a more detailed, formal, objective definition of IBC, the lack of which compromises clinical care, hampers the conduct of clinical trials, and hinders the search for IBC-specific biomarkers and treatments because of the heterogeneity of patients considered to have IBC. METHODS: Susan G. Komen, the Inflammatory Breast Cancer Research Foundation, and the Milburn Foundation convened patient advocates, clinicians, and researchers to review the state of IBC and to propose initiatives to advance the field. After literature review of the defining clinical, pathologic, and imaging characteristics of IBC, the experts developed a novel quantitative scoring system for diagnosis. RESULTS: The experts identified through consensus several "defining characteristics" of IBC, including factors related to timing of onset and specific symptoms. These reflect common pathophysiologic changes, sometimes detectable on biopsy in the form of dermal lymphovascular tumor emboli and often reflected in imaging findings. Based on the importance and extent of these characteristics, the experts developed a scoring scale that yields a continuous score from 0 to 48 and proposed cut-points for categorization that can be tested in subsequent validation studies. CONCLUSION: To move beyond subjective 'clinical diagnosis' of IBC, we propose a quantitative scoring system to define IBC, based on clinical, pathologic, and imaging features. This system is intended to predict outcome and biology, guide treatment decisions and inclusion in clinical trials, and increase diagnostic accuracy to aid basic research; future validation studies are necessary to evaluate its performance.

Zinc as a non-hormonal contraceptive: an alternative to the copper intrauterine device (IUD).

In brief: The many side effects of current contraceptives leave a large proportion of women without adequate protection. This study shows that zinc, a highly physiologically compatible metal, provides effective long-acting reversible contraception in rats, without requiring the use of hormones. Abstract: Long-acting and reversible contraceptives (LARC) are the most widely used form of female contraception worldwide; however, they have significant side effects that often result in early removal. Most LARCs are hormonal, but the use of exogenous hormones is not suitable for all women and causes side effects in many others. The copper IUD (CuIUD) is the only non-hormonal LARC, but a large proportion of users suffer severe side effects. This study proposes the use of zinc as a suitable alternative to the CuIUD. A rat intrauterine device (IUD) model was established to test the efficacy of a zinc IUD (ZnIUD) against a CuIUD. The IUD was surgically implanted into one uterine horn while the other remained untreated. Both the ZnIUD and CuIUD resulted in zero implantation sites which were significantly fewer compared to non-treated horns. Histological assessment revealed damage and inflammation in the endometrium of CuIUD-treated horns but only minor epithelial changes in ZnIUD-treated horns. This suggests ZnIUDs may not share the side effect profile of the CuIUD. To test the long-term efficacy of the ZnIUD, rats had a ZnIUD surgically implanted into both horns and cohoused with males for 3 months. These rats mated regularly but did not get pregnant, confirming long-term effectiveness. Reversibility of the ZnIUD was also established, as removal of the ZnIUD after 3 months resulted in no significant difference in the number of implantation sites between treated and untreated horns. This study demonstrated the contraceptive efficacy of zinc and its potential as a LARC.

Efficient and fabrication error tolerant grating couplers on the InP membrane on silicon platform.

In order to couple light between photonic integrated circuits and optical fibers, grating couplers are commonly employed. This paper describes the design and fabrication of deep and shallow-etched grating couplers with a metal back-reflector with record low insertion losses in InP-based platforms. The measured insertion losses for deep and shallow-etched gratings are 2.4 and 2.6 dB, respectively. Additionally, fabrication error tolerances in shallow etched grating couplers have been examined experimentally, which showed high tolerance of this structure toward the grating period and fill factor.

Effect of diet energy level and genomic residual feed intake on bred Holstein dairy heifer growth and feed efficiency.

The objective of this study was to determine growth, feed intake, and feed efficiency of postbred dairy heifers with different genomic residual feed intake (RFI) predicted as a lactating cow when offered diets differing in energy density. Postbred Holstein heifers (n = 128, ages 14-20 mo) were blocked by initial weight (high, medium-high, medium-low, and low) with 32 heifers per block. Each weight block was sorted by RFI (high or low) to obtain 2 pens of heifers with high and low genomically predicted RFI within each block (8 heifers per pen). Low RFI heifers were expected to have greater feed efficiency than high RFI heifers. Dietary treatments consisted of a higher energy control diet based on corn silage and alfalfa haylage [HE; 62.7% total digestible nutrients, 11.8% crude protein, and 45.6% neutral detergent fiber; dry matter (DM) basis], and a lower energy diet diluted with straw (LE; 57.0% total digestible nutrients, 11.7% crude protein, and 50.1% neutral detergent fiber; DM basis). Each pen within a block was randomly allocated a diet treatment to obtain a 2 × 2 factorial arrangement (2 RFI levels and 2 dietary energy levels). Diets were offered in a 120-d trial. Dry matter intake by heifers was affected by diet (11.0 vs. 10.0 kg/d for HE and LE, respectively) but not by RFI or the interaction of RFI and diet. Daily gain was affected by the interaction of RFI and diet, with low RFI heifers gaining more than high RFI heifers when fed LE (0.94 vs. 0.85 kg/d for low and high RFI, respectively), but no difference for RFI groups when fed HE (1.16 vs. 1.19 kg/d for low and high RFI, respectively). Respective feed efficiencies were improved for low RFI compared with high RFI heifers when fed LE (10.6 vs. 11.8 kg of feed DM/kg of gain), but no effect of RFI was found when fed HE (9.4 vs. 9.5 kg of DM/kg of gain for high and low RFI, respectively). No effect of RFI or diet on first-lactation performance through 150 DIM was observed. Based on these results, the feed efficiency of heifers having different genomic RFI may be dependent on diet energy level, whereby low RFI heifers utilized the LE diet more efficiently. The higher fiber straw (LE) diet controlled intake and maintained more desirable heifer weight gains. This suggests that selection for improved RFI in lactating cows may improve feed efficiency in growing heifers when fed to meet growth goals of 0.9 to 1.0 kg of gain/d.

The COVID-19 pandemic and children with PANS/PANDAS: an evaluation of symptom severity, telehealth, and vaccination hesitancy.

The current study assessed the impact of the COVID-19 pandemic on children with PANS/PANDAS, a condition characterized by sudden-onset obsessive-compulsive, tic, or restrictive eating symptoms following infection. We conducted an anonymous survey between February and June 2021 of 254 self-reported caregivers of minors with PANS/PANDAS. Caregivers answered questions regarding PANS/PANDAS symptoms, telehealth care, and intention to vaccinate their child against COVID-19. PANS/PANDAS symptoms during COVID-19 infections were assessed when applicable. Children's OCD symptoms and coercive behaviors towards caregivers, along with the caregivers' mental health, relationship satisfaction, and burden, were assessed using standardized questionnaires. A majority of respondents endorsed a negative impact on their child's friendships, relationships with extended family, hobbies, and academic skills due to the pandemic. Children with suspected or diagnosed COVID-19 experienced new or worsened psychiatric symptoms, particularly mood lability, OCD, and anxiety. Telehealth care was the preferred treatment modality if the child had mild symptoms of PANS/PANDAS. A majority of caregivers reported high levels of relationship dissatisfaction and caregiver burden. As expected, these data suggest an overall negative impact of the COVID-19 pandemic on children with PANS/PANDAS and their caregivers.

The effect of functioning on Quality of Life Inventory-Disability measured quality of life is not mediated or moderated by parental psychological distress.

PURPOSE: The measurement of quality of life (QOL) in children with intellectual disability often relies upon proxy report via caregivers. The current study investigated whether caregiver psychological distress mediates or moderates the effects of impairment on their ratings of QOL in children with intellectual disability. METHODS: Caregivers of 447 children with an intellectual disability reported their child's day-to-day functioning, their own psychological distress using the Kessler Psychological Distress Scale, and the Quality of Life Inventory-Disability (QI-Disability), a measure of QOL for proxy report of a child's observable behaviours that indicate quality of life. Linear regression was used to assess the effects of the child's functional abilities on their QI-Disability score and causal mediation analysis to estimate the extent to which these effects were mediated by caregivers' psychological distress. RESULTS: A minority of caregivers (n = 121, 27.1%) reported no psychological distress. Lower day-to-day functional abilities, such as being fully dependent on others to manage their personal needs were associated with lower total QOL scores. There was no significant mediation effect of caregiver psychological distress on the association between child functioning and total QOL scores. Moderation analyses revealed small and largely nonsignificant interaction coefficients, indicating that caregiver psychological distress did not influence the strength of the relationship between child functioning and total QOL scores. CONCLUSION: Caregiver psychological distress did not mediate or moderate the relationship between the level of functional abilities and QOL in children with intellectual disability. QI-Disability measured observable child behaviours which may reduce the influence of caregiver factors on the accurate measure of QOL for children with intellectual disability.

Clinical characteristics and disease burden in prurigo nodularis.

BACKGROUND: Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized by intense pruritus, but information on patient experience and impact on quality of life (QoL) remains understudied. AIM: To characterize disease characteristics and QoL in a global sample of patients with PN. METHODS: An anonymous survey was distributed via patient support groups for PN. RESULTS: In total, 231 members responded to the survey. The majority of respondents reported itch localized both to nodules and to intervening skin (67.0%). Associated symptoms included prickling, pain, stinging and burning. The extensor lower legs (69% right, 67.3% left) and flexor forearms (66.1% right, 62% left) were the most common sites of itch. Participants reported frequent healthcare utilization, with 36.3% visiting a doctor ≥ 10 times in the past year. Physician-diagnosed anxiety (45.4%), depression (16.4%) and the atopic triad (18.7%) were commonly reported. Patients with PN had mean scores of 16.4, 11.6 and 16.8 on the Dermatology Life Quality Index, Pittsburgh Sleep Quality Index and 5-Dimensions Itch, respectively. CONCLUSIONS: Severe pruritus with accompanying pain, stinging and burning is characteristic of PN, with the majority of patients experiencing itch in both nodular and interlesional skin. Patients further report decreased QoL scores and impaired sleep. Patient experiences should guide future management of PN.

A study on the use of thermal imaging as a diagnostic tool for the detection of digital dermatitis in dairy cattle.

Our aims were to (1) determine how interdigital skin temperature (IST), measured using infrared thermography, was associated with different stages of digital dermatitis (DD) lesions and (2) develop and validate models that can use IST measurements to identify cows with an active DD lesion. Between March 2019 and March 2020, infrared thermographic images of hind feet were taken from 2,334 Holstein cows across 4 farms. We recorded the maximum temperature reading from infrared thermographic images of the interdigital skin between the heel bulbs on the hind feet. Pregnant animals were enrolled approximately 1 to 2 mo precalving, reassessed 1 wk after calving, and again at approximately 50 to 100 d postpartum. At these time points, IST and the clinical stage of DD (M-stage scoring system: M1-M4.1) were recorded in addition to other data such as the ambient environmental temperature, height, body condition score, parity, and the presence of other foot lesions. A mixed effect linear regression model with IST as the dependent variable was fitted. Interdigital skin temperature was associated with DD lesions; compared to healthy feet, IST was highest in feet with M2 lesions, followed by M1 and M4.1 lesions. Subsequently, the capacity of IST measurements to detect the presence or absence of an active DD lesion (M1, M2, or M4.1) was explored by fitting logistic regression models, which were tested using 10-fold validation. A mixed effect logistic regression model with the presence of active DD as the dependent variable was fitted first. The average area under the curve for this model was 0.80 when its ability to detect presence of active DD was tested on 10% of the data that were not used for the model's training; an average sensitivity of 0.77 and an average specificity of 0.67 was achieved. This model was then restricted so that only explanatory variables that could be practically recorded in a nonresearch, external setting were included. Validation of this model demonstrated an average area under the curve of 0.78, a sensitivity of 0.88, and a specificity of 0.66 for 1 of the time points (precalving). Lower sensitivity and specificity were achieved for the other 2 time points. Our study adds further evidence to the relationship between DD and foot skin temperature using a large data set with multiple measurements per animal. Additionally, we highlight the potential for infrared thermography to be used for routine on-farm diagnosis of active DD lesions.

Peritonsillar Abscess at a Dedicated Otolaryngology Emergency Department.

Aim Peritonsillar abscess (PTA) is the most common suppurative complication of acute tonsillitis. It requires urgent specialist treatment due to the risk of progression to airway compromise. We aimed to review referral pathways to a dedicated otolaryngology emergency department (ORL-ED), identify causative organisms and discuss COVID-19 implications. Methods A retrospective review of patients presenting to the ORL-ED between January 2018 and December 2019 was undertaken. Data extracted included demographics, referral source, treatment, microbiology results and length of stay. Statistical analysis of seasonal variation of presentation and causative organisms employed Chi-Square and Fisher's Exact Test, respectively. Results There were 53 PTA presentations. 51 were admitted accounting for 44.3% (51/115) of ED admissions. The median patient age was 31 years (IQR 20-40yrs). GP referral accounted for 48/53 (90.6%). There was no statistically significant seasonality (χ2=5.94, p=0.11) in presentation. Microbiology samples were available for 44 patients. Streptococcus was identified in 19/44 (43.2%) patients. 85% (45/53) of patients received Co-amoxiclav. Discussion PTA is a perennial condition with diverse causative organisms. Antibiotic choice should reflect this. The majority of patients are referred from primary care, emphasising the role of the GP in initial diagnosis and the importance of clinical education in this regard.

A new method for the high-precision assessment of tumor changes in response to treatment.

Motivation: Imaging demonstrates that preclinical and human tumors are heterogeneous, i.e. a single tumor can exhibit multiple regions that behave differently during both development and also in response to treatment. The large variations observed in control group, tumors can obscure detection of significant therapeutic effects due to the ambiguity in attributing causes of change. This can hinder development of effective therapies due to limitations in experimental design rather than due to therapeutic failure. An improved method to model biological variation and heterogeneity in imaging signals is described. Specifically, linear Poisson modeling (LPM) evaluates changes in apparent diffusion co-efficient between baseline and 72 h after radiotherapy, in two xenograft models of colorectal cancer. The statistical significance of measured changes is compared to those attainable using a conventional t-test analysis on basic apparent diffusion co-efficient distribution parameters. Results: When LPMs were applied to treated tumors, the LPMs detected highly significant changes. The analyses were significant for all tumors, equating to a gain in power of 4-fold (i.e. equivalent to having a sample size 16 times larger), compared with the conventional approach. In contrast, highly significant changes are only detected at a cohort level using t-tests, restricting their potential use within personalized medicine and increasing the number of animals required during testing. Furthermore, LPM enabled the relative volumes of responding and non-responding tissue to be estimated for each xenograft model. Leave-one-out analysis of the treated xenografts provided quality control and identified potential outliers, raising confidence in LPM data at clinically relevant sample sizes. Availability and implementation: TINA Vision open source software is available from www.tina-vision.net. Supplementary information: Supplementary data are available at Bioinformatics online.

Effect of diet energy density and genomic residual feed intake on prebred dairy heifer feed efficiency, growth, and manure excretion.

The objective of this study was to determine the growth, feed efficiency, and manure excretion of prebred dairy heifers with differing predicted genomic residual feed intakes (RFI) when offered diets differing in energy density. Prebred Holstein heifers (n = 128, ages 4 to 8 mo) were blocked by weight (low, medium-low, medium-high, or high) with 32 heifers per block. Heifers in each weight block were grouped by RFI and randomly assigned to obtain 2 pens of high (HRFI) and 2 pens of low RFI (LRFI) heifers within each block (8 heifers/pen). Heifers with LRFI were hypothesized to have greater feed efficiency than HRFI heifers. Dietary treatments were a high-energy diet (HE; 66.6% total digestible nutrients, 14.0% crude protein, and 36.3% neutral detergent fiber, dry matter basis) and a low-energy diet (LE; 63.8% total digestible nutrients, 13.5% crude protein, and 41.2% neutral detergent fiber, dry matter basis). Each pen of heifers was randomly assigned to a treatment to obtain a 2 × 2 factorial arrangement (2 RFI levels × 2 diet energy densities). Diets were offered in a 120-d trial. Dry matter intake was not affected by diet, RFI, or their interaction. Average daily gain (ADG) was affected by diet, with heifers fed HE having greater ADG than heifers fed LE. In addition, RFI affected ADG, with LRFI heifers having greater ADG than HRFI heifers, whereas the interaction of RFI and diet was not significant. Feed efficiency was improved for heifers fed the HE diet, but it was not affected by RFI or the interaction of RFI and diet. Overall, feed efficiency of prebred heifers was not dependent on predicted genomic RFI, because the greater ADG of LRFI heifers was accompanied by slightly higher dry matter intake. Feed efficiency of heifers was reduced when heifers were fed the LE diet, but this resulted in more optimal ADG compared with the HE diet fed for ad libitum intake.

Determination of antimony and barium in UK air quality samples as indicators of non-exhaust traffic emissions.

The aim of this study was to determine concentrations of antimony and barium in air quality samples and assess the potential suitability of these metals as tracer elements for non-exhaust traffic emissions sources. Air quality filters sampled at monitoring sites around the UK for the purposes of the UK Heavy Metals Monitoring Network were subjected to microwave digestion in hydrogen peroxide and nitric acid, then analysed by ICP-MS for a suite of metals including antimony and barium. The average antimony concentration found across all the network sites was 1.84 ng m-3; the average barium concentration was 6.33 ng m-3. The range of antimony concentrations observed was 0.13-8.02 ng m-3; barium concentrations ranged from levels below the detection limit of 0.18 to 39.9 ng m-3. There are no legislative limits for antimony and barium in ambient air, but the maximum concentrations found are well below the Workplace Exposure Limits specified by the UK Health and Safety Executive. The highest concentrations were found at roadside sites situated to monitor traffic environments, supporting the suitability of antimony and barium to be considered tracer elements for traffic emissions sources. Strong correlations were observed between antimony, barium and copper, indicating they share a common traffic-related source. Based on the strong correlation with copper at urban and traffic locations, indicative annual UK atmospheric emission estimates for antimony and barium in brake and tyre wear were calculated as 6 and 19 tonnes respectively.

Early barriers to neonatal porcine islet engraftment in a dual transplant model.

Porcine islet xenografts have the potential to provide an inexhaustible source of islets for ß cell replacement. Proof-of-concept has been established in nonhuman primates. However, significant barriers to xenoislet transplantation remain, including the poorly understood instant blood-mediated inflammatory reaction and a thorough understanding of early xeno-specific immune responses. A paucity of data exist comparing xeno-specific immune responses with alloislet (AI) responses in primates. We recently developed a dual islet transplant model, which enables direct histologic comparison of early engraftment immunobiology. In this study, we investigate early immune responses to neonatal porcine islet (NPI) xenografts compared with rhesus islet allografts at 1 hour, 24 hours, and 7 days. Within the first 24 hours after intraportal infusion, we identified greater apoptosis (caspase 3 activity and TUNEL [terminal deoxynucleotidyl transferase dUTP nick end labeling])-positive cells) of NPIs compared with AIs. Macrophage infiltration was significantly greater at 24 hours compared with 1 hour in both NPI (wild-type) and AIs. At 7 days, IgM and macrophages were highly specific for NPIs (α1,3-galactosyltransferase knockout) compared with AIs. These findings demonstrate an augmented macrophage and antibody response toward xenografts compared with allografts. These data may inform future immune or genetic manipulations required to improve xenoislet engraftment.

Rate-equation theory of a feedback insensitive unidirectional semiconductor ring laser.

For our recently designed continuous-wave and single-frequency ring laser with intra-cavity isolator, we have formulated a rate-equation theory which accounts for two sources of mutual back-scattering between the clockwise and counterclockwise modes, i.e. induced by side-wall irregularities and due to inversion-grating-induced spatial hole burning. With this theory we first confirm that for a ring laser without intra-cavity isolation, from sufficiently large pumping strength on, the inversion-grating-induced bistable operation (i.e. either clockwise or counterclockwise) will overrule the back-reflection-induced coupled-mode operation (i.e. both clockwise and counterclockwise). We then analyze the robustness of unidirectional operation in case of intra-cavity isolation against the intra-cavity back-reflection mechanism and grating-induced mode coupling and derive for this case an explicit expression for the directionality in the presence of external optical feedback, valid for sufficiently strong isolation. The predictions posed in the second reference remain unaltered in the presence of the mode coupling mechanisms here considered.

Model and experimental validation of a unidirectional phase modulator.

A unidirectional phase modulator consisting of tandem phase modulators is studied in detail for use as an integral part of an integrated optical isolator. The effects of non-linearity and residual amplitude modulation in the modulators, as well as the effect of the RF driving signals are captured in a phenomenological model for the first time. The model has been verified experimentally using a device realized in a generic InP based photonic integration platform and is used to study the operating range of the device. Design parameters of the modulator are derived such that modulation side bands in the forward propagating light are less than 40 dB, while isolation is maximized.

Immunogenicity of sequential 13-valent conjugated and 23-valent unconjugated pneumococcal vaccines in a population of children with lupus.

Pneumococcal vaccination is recommended as a quality indicator for management of children with systemic lupus erythematosus. Literature on the immunogenicity of pneumococcal vaccines (PCVs) in children is scant. We sought to prospectively evaluate via an observational study, the immunogenicity to sequential children with lupus. Out of a cohort of 26 patients, approximately 65% achieved > 70% vaccinated serotype antibody levels of > 1.3 mcg/dL following PCV13, and of 22 patients followed through PPSV23 vaccination, 59% achieved the same. Patients with rituximab exposure in the 6 months prior to a vaccination were more likely to not achieve protective serotype levels ( p < 0.01 for PCV13, trend p = 0.07 for PPSV23). Three of 22 patients with no apparent risk factors did not achieve protective serotype levels. Non-responders to PCV13 generally did not respond to PPSV23. Retrospective healthy controls achieved 100% protective levels in response to PPSV23 vaccination, with 95% of serotypes being > 1.3 mcg/dL. Thus, sequential 13- and 23-valent pneumococcal vaccines achieve protective status for approximately two thirds of pediatric lupus patients in our population. Lack of response to vaccine may be secondary to induced or inherent functional impairments in the patient.