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Numerous studies provide critical analyses of TV minority representations but only few examine successful portrayals. Moreover, there is no consensus on what makes a given depiction successful and how to measure it. Bringing insights from representation studies and media psychology, we propose that successful representations showcase minorities in a way which may foster audience engagement with characters and improve their diversity attitudes. In the current project, we developed a quantitative content analysis codebook with the following representation strategies: portrayal of minority experiences, recognizable representation, attractive representation, psychological depth, stereotypical representation, and friendly interactions. We demonstrate our approach by analyzing the portrayal of non-heterosexual and Black characters in Sex Education. We coded all the scenes with Eric, Adam, and Jackson from the first season of the TV show. Results indicate that these characters are predominantly shown as recognizable to viewers and in friendly interactions with other people. Moreover, they are depicted with attractive personality traits, and indicators of psychological depth. They also undergo various minority experiences. Some stereotypes about gay men are shown but anti-Black stereotypes are rare. In the results’ discussion, we suggest different ways of using our codebook in future studies.

Nanostring data from tumor biopsies.

Supplementary Table S1. Anti-PD-1/L1 treatment experience by SD-101 dose group. Supplementary Table S2. Overview of safety. Supplementary Table S3. Treatment-related events in 20% or more of patients in the total treatment cohort are presented. Supplementary Figure S1.Percent change from baseline over time in tumors in patients who were naïve to anti-PD-1/L1 therapy. Supplementary Figure S2. IFN gene signature in Blood Cells. Supplementary Figure S3. RNA gene expression profiling. Supplementary Figure S4. A subset of patient biopsies that were assessed by RNA expression profiling, were assessed by fluorescent immunohistochemistry for infiltration of CD4 (A) and CD8 (B) T cells. Supplementary Figure S5. Correlation between fluorescent immunohistochemistry (IHC) and RNA expression profiling by Nanostring.

Background: Hepatitis B virus (HBV) infection remains a significant global burden, especially for patients with chronic kidney disease (CKD) receiving hemodialysis. Three doses of HepB–CpG (HEPLISAV-B® vaccine) induced a superior immune response compared with 4 double doses of HepB–Eng (Engerix-B®) in a phase 3 trial (HBV-17) in adults with CKD. Here we report the long-term immunogenicity and safety of HepB-CpG and HepB–Eng in eligible participants of HBV-17 who enrolled in this optional 34-month follow-up trial (HBV-19). Methods: HBV-19 is a multicenter, open-label, phase 3b trial of adults with CKD who previously received a complete series of HepB-CpG or HepB-Eng in the HBV-17 trial. Participants were assigned to seroprotection categories at enrollment on the basis of their antibody response to hepatitis B surface antigen (anti-HBs) in HBV-17. The objective was to evaluate the durability of seroprotection (defined as an anti-HBs concentration ≥ 10 mIU/mL) induced by HepB-CpG and HepB-Eng. Participants whose anti-HBs concentration was below 10 mIU/mL received additional HepB-CpG or HepB-Eng doses. Results: 147 participants were enrolled; 66.7 % were men, median age was 65.0 years, and 83.7 % were white. The durability of seroprotection in participants with CKD was similar in those who received HepB-CpG and those who received HepB-Eng. Antibody concentrations ≥ 100 mIU/mL persisted for longer in HepB-CpG than HepB-Eng recipients, among those with anti-HBs ≥ 100 mIU/mL post vaccination. The geometric mean anti-HBs concentration in the HepB-CpG group was significantly higher than in the HepB-Eng group over time (P ≤ 0.0001). The safety profiles were similar between the vaccine groups. Conclusions: Due to the higher antibody levels induced by HepB-CpG in participants with CKD, seroprotection against HBV may be expected to persist longer than that induced by HepB-Eng. ClinicalTrials.gov: NCT01282762.

Background In the absence of field efficacy studies, estimating the real-world effectiveness of vaccines may consider immunogenicity from randomized controlled clinical trials and real-world adherence. Combining seroprotection rates (SPRs) with regimen completion rates gives an estimate of an effective vaccine protection rate (eVPR), which can be leveraged to evaluate real-world cost-effectiveness by linking it with vaccine costs to estimate the cost-per-protected patient (CPP). Methods This study evaluated eVPR and CPP as estimates of vaccine clinical- and cost-effectiveness of two-dose (HepB-CpG) and three-dose (HepB-Alum) hepatitis B virus (HBV) vaccines in the general adult population and a subpopulation with diabetes mellitus. eVPR was calculated from head-to-head SPR data from phase 3 clinical trials directly comparing HepB-CpG and HepB-Alum vaccine regimens and real-world head-to-head adherence data. CPP was calculated as the average cost of each regimen divided by eVPR. Results Higher eVPR in the adult population was achieved with HepB-CpG (68.0%) versus HepB-Alum (41.6%), reflecting the combination of higher SPR and vaccine regimen completion. The CPP for HepB-CpG ($331.31) was $45.67 (95% CI: $36.66, $55.19) less than HepB-Alum ($377.09). Greater savings were observed among persons with diabetes, with CPP $149.60 (95% CI: $80.29, $195.63) lower with HepB-CpG ($367.57) than HepB-Alum ($517.37). Conclusions Metrics estimating vaccine real-world effectiveness and value may guide informed decisions in vaccine selection. For example, using eVPR and CPP, HepB-CpG represents a more effective, value-advantaged approach than HepB-Alum toward reducing HBV infection.

This study compared the immunogenicity and safety of a booster dose of HepB-CpG (HEPLISAV-B® vaccine) with HepB-Eng (Engerix-B®) and HepB-AS04 (Fendrix®) in patients receiving chronic hemodialysis. This was a multicenter, randomized, open-label, phase 3 study of adults receiving hemodialysis with antibodies to HBsAg (anti-HBs)10 mIU/mL at study entry. The objective was to compare the seroprotection rate (SPR) induced by HepB-CpG with HepB-Eng or HepB-AS04. The SPR was defined as the percentage of patients with anti-HBs ≥10 mIU/mL post-vaccination. At 20 sites in Germany, 155 participants were randomized: HepB-CpG = 54; HepB-Eng = 50; and HepB-AS04 = 51. Of the 149 participants in the modified intention-to-treat population, 76.5% had not previously responded to at least one series of hepatitis B vaccine. Based on a post hoc analysis, the SPR in HepB-CpG recipients (52.8%; 95% confidence interval [CI]: 38.6%, 66.7%) was significantly higher than in HepB-Eng recipients (32.6%; 95% CI: 19.5%, 48.0%), and non-inferior to that in HepB-AS04 recipients (43.1%; 95% CI: 29.3%, 57.8%). Local post-injection reactions occurred in significantly fewer HepB-CpG (9.3%) than HepB-AS04 recipients (31.4%

ZusammenfassungWir präsentieren den Fall einer 83-jährigen Patientin mit einem bullösen Pemphigoid (BP) unter Aussparung des linken Armes bei Zustand nach axillärer Lymphadenektomie nach Mammakarzinom. Lokalisierte Formen des bullösen Pemphigoids treten v. a. bei Lymphödemen oder nach Radiatio auf. Das Fehlen des Blasenbefalls nach einer Lymphadenektomie stellt eine seltene und interessante Manifestation dar. Pathophysiologisch könnte durch den Rückgang der T‑Zell-Aktivierung bei fehlenden peripheren Lymphknoten und somit vermindertem entzündlichem Infiltrat die Blasenbildung abgeschwächt sein bzw. vollkommen ausbleiben.

This article presents an evaluation of 4255 autopsy cases recorded at the Dusseldorf Pathology Institute in the years 1914 to 1918. Diagnoses were coded according to the International Classification of Diseases, 10th edition (ICD-10), and the contemporaneous history of the Pathology Institute was reviewed. We found a proportion of 54.1% adults and 45.5% children in our cohort, with a male predominance of 63.9%. Infectious diseases account for the majority of all cases (35.5%), among which tuberculosis is the most frequent, reported in 22.7% of all cases. The second largest diagnosis group is the one of respiratory diseases (16.9%), including pneumonia and influenza. Cases of perinatal conditions account for 10.5% of the collective, followed by neoplasms, injuries, intoxications, or external causes, each representing 6.6%. Cardiovascular diseases account for 5.3% of the cases. In 4.4% of the pediatric and 0.8% of adult cases, a diagnosis of the ICD-10 group “nutritional and endocrine diseases” was made. No diagnosis of hunger edema is reported. Parts of the cohort are 272 war pathology cases (6.4%), made up by soldiers who mainly had died of shotgun injuries. The whole cohort represents the disease spectrum of a German big city population at times of World War I. The data exemplify the epidemiological shift that has occurred in industrialized countries over the last 100 years, from infectious to neoplastic and cardiovascular diseases.

Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Radboud University Medical CenterAcademic Alliance Fund Maastricht - Nijmegen Background Current sports medical examinations do not appropriately detect occult coronary atherosclerosis in athletes, whereas coronary atherosclerosis is more prevalent in middle-aged and older athletes compared to physically active controls. Therefore, new diagnostic approaches need to be developed to identify individuals at risk. Cardiac troponin (cTn) is the standard biomarker to assess myocardial injury. Exercise is known to increase cTn concentrations and a delayed recovery of cTn concentrations after exercise cessation is suggested to be indicative of occult obstructive coronary artery disease. We hypothesized that the magnitude of exercise-induced cTn elevations may be associated with the degree of coronary atherosclerosis. Purpose To compare serial measures of exercise-induced cTnT elevations across middle-aged and older athletes with different degrees of coronary atherosclerosis. Methods A subgroup of 59 men from the Measuring Athlete’s Risk of Coronary events-2 study (MARC-2, n=291) were invited for this add-on study. All participants had undergone a cardiac computed tomography (CT) scan and coronary CT angiography to determine the prevalence and magnitude of coronary atherosclerosis. Athletes were stratified based on the degree of coronary atherosclerosis: I) n=20 with a coronary artery calcium score (CACS) of 0, II) n=20 with CACS ≥300 or ≥75th MESA-percentile, and III) n=19 with a >50% stenosis in any coronary artery, but without ischemia on a stress imaging tests. Participants performed an individualized exercise test (>1 hour, cycling) until volitional exhaustion. High-sensitivity cTnT concentrations were measured at baseline, after 30 minutes of exercise and at 0, 30, 60, 120, and 180 minutes post-exercise. Results Participants (age 60.8 [57.9-72.6] years, BMI 24.5 [23.9-27.3]) exercised for 76±14 minutes, up to 97.6 [94.4-101.8] % of their expected maximum heart rate. Exercise duration and workload did not differ across groups. Baseline hs-cTnT was detectable in everyone. Exercise induced a 1.98±1.63 fold increase in hs-cTnT concentrations. Peak hs-cTnT concentrations occurred at 180 minutes post-exercise (13.9 [9.4-17.0] ng/L versus 12.1 [10.0-21.5] ng/L versus 13.8 [9.1-19.9] ng/L, for group I, II and III, respectively) and the incidence of hs-cTnT concentrations above the URL (n=9 (45%) vs n=7 (35.0%) vs n=9 (47.4%)) was comparable across groups (p=0.92 and p=0.71, respectively). Patterns of time-dependent changes in hs-cTnT concentrations did not differ across groups (p=.49). Conclusion Exercise-induced elevations in hs-cTnT concentrations did not differ among middle-aged and older athletes with different degrees of coronary atherosclerosis. Our findings suggest that hs-cTnT sampled before, during or within 180 minutes following an exhaustive endurance cycling exercise test is not suitable to detect occult coronary atherosclerosis in athletes.

Detailed validation of air quality models is essential, but remains challenging, due to a lack of suitable high-resolution measurement datasets. This is particularly true for pollutants with short-scale spatial variations, such as nitrogen dioxide (NO2). While street-level air quality model chains can predict concentration gradients at high spatial resolution, measurement campaigns lack the coverage and spatial density required to validate these gradients. Citizen science offers a tool to collect large-scale datasets, but it remains unclear to what extent such data can truly increase model performance. Here we use the passive sampler dataset collected within the large-scale citizen science campaign CurieuzeNeuzen to assess the integrated ATMO-Street street-level air quality model chain. The extensiveness of the dataset (20.000 sampling locations across the densely populated region Flanders, ∼1.5 data points per km2) allowed an in-depth model validation and optimization. We illustrate generic techniques and methods to assess and improve street-level air quality models, and show that considerable model improvement can be achieved, in particular with respect to the correct representation of the small-scale spatial variability of the NO2-concentrations. After model optimization, the model skill of the ATMO-Street chain significantly increased, passing the FAIRMODE model quality threshold, and thus substantiating its suitability for policy support. More generally, our results reveal how a “deep validation” based on extensive spatial data can substantially improve model performance, thus demonstrating how air quality modelling can benefit from one-off large-scale monitoring campaigns.

A 56-year-old, otherwise healthy, man was referred to the Academic Tattoo Clinic Amsterdam because of pain and itch in a multicoloured tattoo on his right arm since one month. Two weeks before the start of the complaints the patient had gotten the tattoo in Bali, Indonesia. The patient had no fever or other physical complaints. Physical examination revealed multiple erythematosquamous papules and pustules, especially in the black and white coloured parts of the tattoo (Fig. 1a).

An 83-year-old woman presented to our outpatient clinic with bullous pemphigoid with a unilateral sparing of the left arm after axillary lymphadenectomy because of breast cancer. Cases of localized manifestations of bullous pemphigoid are mainly caused by lymphedema or radiation. The absence of blistering after lymphadenectomy is a rare and interesting manifestation. Pathophysiologically, blister formation may be attenuated or absent altogether due to decreased T‑cell activation and thus reduced inflammatory infiltrate because of the absence of peripheral lymph nodes.Wir präsentieren den Fall einer 83-jährigen Patientin mit einem bullösen Pemphigoid (BP) unter Aussparung des linken Armes bei Zustand nach axillärer Lymphadenektomie nach Mammakarzinom. Lokalisierte Formen des bullösen Pemphigoids treten v. a. bei Lymphödemen oder nach Radiatio auf. Das Fehlen des Blasenbefalls nach einer Lymphadenektomie stellt eine seltene und interessante Manifestation dar. Pathophysiologisch könnte durch den Rückgang der T‑Zell-Aktivierung bei fehlenden peripheren Lymphknoten und somit vermindertem entzündlichem Infiltrat die Blasenbildung abgeschwächt sein bzw. vollkommen ausbleiben.

Hurricane Michael made landfall as a Category 5 Hurricane on 10 October 2018 between Mexico Beach, Florida and Tyndall Air Force Base in Panama City Beach, Florida causing damages totaling $25 billion (Beven et al. 2019). While damages were caused by both wind and surge, this paper is solely concerned with the surge induced damages which were observed predominantly within 50 km (27 nmi) of the hurricane’s path. Generally, regions to the east of Hurricane Michael’s landfall sustained the most severe damages and appear consistent with the spatial gradient in peak water levels. This gradient was marked; with surge induced damage concentrated in the immediate vicinity of Mexico Beach and attenuating significantly over distances as little as 37 km (20 nmi) to the west in Panama City Beach and east in Port Saint Joe (Kennedy, in review). The gradient in erosion was also pronounced, with Panama City Beach experiencing an average erosion rate of 0.4 m3/m (3.9 cy/ft) while Mexico Beach and Cape San Blas experienced rates approximately three (1.1 m3/m or 11.5 cy/ft) and five (1.7 m3/m or 18.5 cy/ft) times that. For inherent reasons, the pronounced gradient in surge damages and erosion values are of primary interest to coastal researchers and managers. Storm Erosion Index (SEI), developed by Miller and Livermont (2008) combines the three primary drivers of coastal erosion (wave height, total water level, and storm duration) into a physically meaningful form to evaluate storms based on their erosion potential. Here, SEI is applied to explore these spatial variations at seven distinct regions within the Florida Panhandle and are compared to the observed impacts for both erosion and structural damages. These regions include: (west to east) Panama City Beach, Tyndall Air Force Base (AFB), Mexico Beach, Cape San Blas, Port St. Joe, St. Vincent Island, and St. George Island. Empirically, the cumulative SEI relates well with the observed beach erosion; while the Peak Erosion Intensity (PEI) was found to better capture the trends in structural damages. By capturing the spatial variation of the storm intensity, SEI and PEI are therefore proposed as a viable engineering demand parameter with potential applications in community scale fragility curves.

Background & Aims: Antiviral treatment from hepatitis B envelope antigen (HBeAg)-positive status may attenuate the integration of hepatitis B virus DNA into the host genome causing hepatocellular carcinoma (HCC). We investigated the impact of HBeAg status at the onset of antiviral treatment on the risk of HCC. Methods: The incidence of HCC was evaluated in Korean patients with chronic hepatitis B who started entecavir or tenofovir in either HBeAg-positive or HBeAg-negative phase. The results in the Korean cohort were validated in a Caucasian PAGE-B cohort. Results: A total of 9143 Korean patients (mean age, 49.2 years) were included: 49.1% were HBeAg-positive and 49.2% had cirrhosis. During follow-up (median, 5.1 years), 916 patients (10.0%) developed HCC. Baseline HBeAg positivity was not associated with the risk of HCC in the entire cohort or cirrhotic subcohort. However, in the non-cirrhotic subcohort, HBeAg positivity was independently associated with a lower risk of HCC in multivariable (adjusted hazard ratio [aHR], 0.41; 95% confidence interval [CI], 0.26–0.66), propensity score-matching (aHR, 0.46; 95% CI, 0.28–0.76), and inverse probability weighting analyses (aHR, 0.44; 95% CI, 0.28–0.70). In the Caucasian cohort (n = 719; mean age, 51.8 years; HBeAg-positive, 20.3%; cirrhosis, 34.8%), HBeAg-positivity was not associated with the risk of HCC either in the entire cohort or cirrhotic subcohort. In the non-cirrhotic subcohort, none of the HBeAg-positive group developed HCC, although the difference failed to reach statistical significance (aHR, 0.21; 95% CI, 0.00–1.67). Conclusions: This multinational cohort study implies that HBeAg positivity at the onset of antiviral treatment seems to be an independent factor associated with a lower risk of HCC in patients with chronic hepatitis B without cirrhosis, but not in those with cirrhosis. © 2021 AGA Institute

Background: This was a phase 1, dose-escalation open-label trial to evaluate the safety and immunogenicity of MVC-COV1901, a SARS-CoV-2 S-2P protein vaccine adjuvanted with aluminum hydroxide and CpG 1018. Methods: 45 healthy adults from 20 to 49 years of age were to be administered two vaccinations of MVC-COV1901 in doses of 5 μg, 15 μg, or 25 μg of spike protein at 28 days apart. There were 15 participants in each dose group; all were followed for 28 days after the second vaccination at the time of the interim analysis. Adverse events (AEs) and laboratory data were recorded for the safety evaluation. Blood samples were collected for wild-type SARS-CoV-2 and pseudovirus neutralization assays, SARS-CoV-2 spike-specific immunoglobulin G (IgG), and cellular immune response at various time points. Findings: Solicited adverse events were mostly mild and similar in all three dose groups. No subject experienced fever. After the second vaccination, serum neutralizing activity for wild-type virus was detected in all participants of the 15 μg and 25 μg dose groups with geometric mean values (76•3 [95% CI: 53•75 ~108•33], and 167•4 [95% CI: 122.05 ~229.61]) 1•8 to 3•9 times those of a panel of control convalescent serum specimens (42•7, [95%CI: 26•38~69•04]). The cellular immune response induced by MVC-COV1901 demonstrated substantially higher numbers of IFN-γ- than IL-4- producing cells in human peripheral blood mononuclear cells, suggesting a Th1-skewed immune response. Interpretation: The MVC-COV1901 vaccine was well tolerated and elicited robust immune responses especially in the 15 μg and 25 μg dose groups and is suitable for further development. Trial Registration: ClinicalTrials.gov NCT 04487210 Funding: Medigen Vaccine Biologics Corporation. Conflict of Interest: Szu-Min Hsieh, Shan-Chwen Chang, Wang-Da Liu, Yu-Shan Huang declared that they have no knowncompeting financial interests or personal relationships that could have appeared to influence the work reported in this paper; Yi-Jiun Lin, Erh-Fang Hsieh, Wei-Cheng Lian, Charles Chen, I-Chen Tai are employee ofMedigen Vaccine Biologics Corporation and reported grants from Taiwan Centers for Disease Control, Ministry of Health and Welfare, during the conduct of the study. In addition, Yi-Jiun. Lin and Charles Chen have a patent US63/040,696 pending. Robert Janssen is an employee of Dynavax Technologies Corporation. Ethical Approval: The trial protocol and informed consent form were approved by the Taiwan Food and Drug Administration and the ethics committee at the site. The trial was conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. An independent data and safety monitoring board (DSMB) was established to monitor safety data and the trial conduct.

Background Hemodialysis patients are at increased risk of hepatitis B virus (HBV) infection and are poorly responsive to HBV vaccines. Current vaccine recommendations for hemodialysis patients utilize more than twice the amount of hepatitis B surface antigen (HBsAg) used for healthy adults and achieve lower immune responses. Methods An open-label, single-arm, multicenter trial was conducted among adults 18 years of age and older who were initiating or undergoing hemodialysis who had not previously received hepatitis B vaccine. Participants received four doses of HepB-CpG (HEPLISAV-B®) (20 mcg rHBsAg + 3000 mcg CpG 1018, a Toll-like receptor 9 agonist) administered at 0, 4, 8, and 16 weeks. Participants are being followed for 68 weeks. This paper reports the final immunogenicity analysis of the primary endpoint at study week 20 and an interim safety analysis. Results We enrolled 119 participants receiving hemodialysis who were followed for a median of 47.4 weeks. Of the 119 participants, 75 were in the per-protocol population. At week 20, the seroprotection rate (% with antibodies to hepatitis B surface antigen [anti-HBs] ≥ 10 mIU/mL) was 89.3% and the percentage of participants with anti-HBs ≥ 100 mIU/mL was 81.3%. The anti-HBs geometric mean concentration was 1061.8 mIU/mL. HepB-CpG was well tolerated with no observed safety concerns. Conclusion In patients receiving hemodialysis, HepB-CpG given as four doses was well tolerated and induced very high anti-HBs concentrations and seroprotection in a very high proportion of recipients.

The hepatitis B virus is highly infectious and can cause incurable liver disease, leading to high morbidity rates, increased healthcare utilization, and high mortality. Multiple preventative hepatitis B vaccine options have been available for decades, but adherence to the traditional 6-month vaccine schedule for the approved 3-dose series remains low in adult populations at risk of hepatitis B exposure. A 2-dose hepatitis B vaccine (HEPLISAV-B) approved by the US Food and Drug Administration in 2017 induces rapid seroprotection within 1 month and has a safety profile comparable to a commonly used 3-dose vaccine. In a previous cost-effectiveness study, HEPLISAV-B had a favorable cost-effectiveness profile for multiple at-risk populations. The goal of the current analysis was to update and extend previous findings by evaluating cost-effectiveness of HEPLISAV-B compared with a 3-dose vaccine (Engerix-B) in selected adult populations, including patients with diabetes, chronic liver or kidney disease, end-stage renal disease, healthcare personnel, travelers to countries with endemic hepatitis B, and a public health population. Cost-effectiveness was measured as incremental cost-effectiveness ratios using a health economics Markov model that accounts for adherence rates, seroprotection rates, healthcare costs, and current pricing considerations. Patients progressed between a series of health states, and the difference in lifetime spending and survival for individuals receiving either HEPLISAV-B or Engerix-B was estimated from the perspective of a US managed care payer, HEPLISAV-B had favorable cost-effectiveness profiles for patients with diabetes, healthcare personnel, travelers, and patients with chronic liver disease and dominant incremental cost-effectiveness ratios for patients with chronic kidney disease and end-stage renal disease. A probabilistic sensitivity analysis supported the robustness of the cost-effectiveness profiles, and an additional analysis indicated that HEPLISAV-B was cost-effective in the general adult population. Overall, HEPLISAV-B was cost-effective in multiple adult populations recommended for HBV vaccination in the United States.

This article presents an evaluation of 4255 autopsy cases recorded at the Dusseldorf Pathology Institute in the years 1914 to 1918. Diagnoses were coded according to the International Classification of Diseases, 10th edition (ICD-10), and the contemporaneous history of the Pathology Institute was reviewed. We found a proportion of 54.1% adults and 45.5% children in our cohort, with a male predominance of 63.9%. Infectious diseases account for the majority of all cases (35.5%), among which tuberculosis is the most frequent, reported in 22.7% of all cases. The second largest diagnosis group is the one of respiratory diseases (16.9%), including pneumonia and influenza. Cases of perinatal conditions account for 10.5% of the collective, followed by neoplasms, injuries, intoxications, or external causes, each representing 6.6%. Cardiovascular diseases account for 5.3% of the cases. In 4.4% of the pediatric and 0.8% of adult cases, a diagnosis of the ICD-10 group "nutritional and endocrine diseases" was made. No diagnosis of hunger edema is reported. Parts of the cohort are 272 war pathology cases (6.4%), made up by soldiers who mainly had died of shotgun injuries. The whole cohort represents the disease spectrum of a German big city population at times of World War I. The data exemplify the epidemiological shift that has occurred in industrialized countries over the last 100 years, from infectious to neoplastic and cardiovascular diseases.

In 2018 the first Dutch guideline on necrotizing soft tissue infections (NSTIs) was drafted. Its aim is to standardize the care of this disease in order to reduce variation, and thereby improve the quality of care. This guideline is a benchmark for all healthcare providers who deal with this devastating disease; it focuses on diagnostics, treatment options and organization of care. Given the low incidence, the complexity and the fulminant course of NSTIs, it is important to ensure continuous specialized care. Therefore it is recommended to make regional agreements about referral to specialized centres. Surgical exploration remains the gold standard for diagnosis. The empirical antibiotic regimen depends on if the onset of disease is community or nosocomial, and if its aetiology is a monomicrobial (type I) or a polymicrobial (type II). The guideline recommends that intravenous immunoglobulin (IVIg) therapy be started if gram staining reveals streptococci. IVIg must be discontinued if group-A streptococcus is excluded as a causative agent.

Background Hepatitis B virus infection remains an important global public health problem. Approved alum-adjuvanted vaccines are well tolerated but require three doses and have reduced immunogenicity in adults. A two-dose vaccine containing hepatitis B surface antigen combined with a novel, Toll-like receptor 9 agonist adjuvant (HBsAg-1018 [HEPLISAV–B®]) has demonstrated significantly higher seroprotection rates than a three dose vaccine. Methods A post hoc analysis compared the safety of HBsAg-1018 with HBsAg-Eng (Engerix-B®), in three randomized, observer-blinded, active-controlled, multi-center phase 3 trials in adults. HBsAg-1018 was administered intramuscularly at weeks 0 and 4 and placebo at week 24 and HBsAg-Eng at weeks 0, 4, and 24. Results Post-injection reactions, adverse events, medically attended adverse events, and new-onset immune-mediated adverse events were balanced between vaccine groups. Anti-nuclear antibodies, anti-double stranded DNA antibodies, anti-neutrophil cytoplasmic antibodies, and antiphospholipid antibodies were balanced between groups. A transient increase in anti-beta2 glycoprotein 1 IgM was observed in the HBsAg-1018 group but was not associated with a thrombotic event. Serious adverse events and deaths were generally balanced between groups. Conclusion HBsAg-1018 had a similar safety profile to HBsAg-Eng. With improved immunogenicity and fewer doses over a shorter time, HBsAg-1018 has the potential to provide improved seroprotection and a significant public health benefit to adults 18 years of age or older.

Background Hepatitis B virus infection remains an important public health problem in the United States. Currently approved alum-adjuvanted vaccines require three doses and have reduced immunogenicity in adults, particularly in those who have diabetes mellitus, or are older, male, obese, or who smoke. Methods Phase 3 observer–blinded, randomized (2:1 HBsAg-1018 [HEPLISAV-B™]:HBsAg-Eng [Engerix-B®]), active–controlled trial in adults 18–70 years of age. HBsAg-1018 was administered intramuscularly at weeks 0 and 4 and placebo at week 24 and HBsAg-Eng at weeks 0, 4, and 24. The primary immunogenicity endpoint assessed the noninferiority of the seroprotection rate at week 28 in participants with type 2 diabetes mellitus. Secondary endpoints included seroprotection rates in the total trial population and by age, sex, body mass index, and smoking status. Results Among 8374 participants randomized, 961 participants in the per-protocol population had type 2 diabetes mellitus. In diabetes participants, the seroprotection rate in the HBsAg-1018 group at week 28 was 90.0%, compared with 65.1% in the HBsAg-Eng group, with a difference of 24.9% (95% CI: 19.3%, 30.7%), which met the prospectively-defined criteria for noninferiority and statistical significance. In the total study per-protocol population (N = 6826) and each pre-specified subpopulation, the seroprotection rate in the HBsAg-1018 group was statistically significantly higher than in the HBsAg-Eng group. Conclusion Two doses of HBsAg-1018, administered over 4 weeks, induced significantly higher seroprotection rates than three doses of HBsAg-Eng, given over 24 weeks, in adults with factors known to reduce the immune response to hepatitis B vaccines as well as in those without those factors. With fewer doses in a shorter time, and greater immunogenicity, HBsAg-1018 has the potential to significantly improve protection against hepatitis B in adults at risk for hepatitis B infection. Trial Registration clinicaltrials.gov Identifier: NCT02117934.

Importance Receipt of hepatitis B virus vaccine is important to prevent infection. However, adherence to the hepatitis B vaccine series among adults at risk of infection has been low. Objective To assess whether recipients of a 2-dose hepatitis B vaccine with cytosine phosphoguanine adjuvant (HepB-CpG vaccine; Heplisav-B) are more likely to complete their series compared with recipients of a 3-dose vaccine with alum adjuvant (comparator vaccine; Engerix-B [HepB-alum]). Design, Setting, and Participants This nested cohort study was conducted from August 7 to December 31, 2018, at Kaiser Permanente Southern California, an integrated health care system with a diverse population of approximately 4.6 million members. Adults not receiving dialysis who received a first dose of a hepatitis B vaccine series in family practice or internal medicine departments of 15 Kaiser Permanente Southern California medical centers were followed up through electronic health records for up to 1 year after receipt of the first dose. Data were analyzed from March 16 to September 23, 2020. Exposures Receipt of a first dose of the HepB-CpG vaccine (2-dose vaccine) vs receipt of a first dose of the HepB-alum vaccine (3-dose vaccine). Main Outcomes and Measures Series completion within the recommended vaccine schedule plus 3 months (primary outcome) and series completion within 1 year after receipt of the first dose (secondary outcome). Results Of 4727 individuals who initiated the HepB-CpG vaccine series and 6161 individuals who initiated the HepB-alum vaccine series included in the study, 2876 (60.8%) and 3789 (61.5%), respectively, were ages 40 to 59 years, 2415 (51.1%) and 3113 (50.5%) were male, and 2364 (50.0%) and 2881 (46.8%) were Hispanic. The vaccine series was completed within the recommended schedule plus 3 months for 2111 (44.7%) individuals who initiated the HepB-CpG vaccine series and 1607 (26.1%) individuals who initiated the HepB-alum vaccine series, and within 1 year for 2858 (60.5%) and 1989 (32.3%) individuals, respectively. The individuals who initiated the HepB-CpG vaccine series were significantly more likely to complete the series (adjusted relative risk, 1.77; 95% CI, 1.68-1.87). Results were consistent across clinical and demographic strata. Conclusions and Relevance In this study, use of the HepB-CpG vaccine was associated with hepatitis B vaccine series completion, but tailored strategies to increase completion of hepatitis B vaccine series are warranted.

The start of complementary feeding in infancy plays an essential role in promoting healthy eating habits. Evidence shows that it is important what infants are offered during this first introduction of solid foods: e.g. starting exclusively with vegetables is more successful for vegetable acceptance than starting with fruits. How infants are introduced to solid foods also matters: if parents are sensitive and responsive to infant cues during feeding, this may promote self-regulation of energy intake and a healthy weight. However, the effectiveness of the what and the how of complementary feeding has never been experimentally tested in the same study. In the current project the what and how (and their combination) are tested in one study to determine their relative importance for fostering vegetable acceptance and self-regulation of energy intake in infants. A four-arm randomized controlled trial (Baby’s First Bites (BFB)) was designed for 240 first-time Dutch mothers and their infants, 60 per arm. In this trial, we compare the effectiveness of (a) a vegetable-exposure intervention focusing on the what in complementary feeding; (b) a sensitive feeding intervention focusing on the how in complementary feeding, (c) a combined intervention focusing on the what and how in complementary feeding; (d) an attention-control group. All mothers participate in five sessions spread over the first year of eating solid foods (child age 4–16 months). Primary outcomes are vegetable consumption, vegetable liking and self-regulation of energy intake. Secondary outcomes are child eating behaviors, child anthropometrics and maternal feeding behavior. Outcomes are assessed before, during and directly after the interventions (child age 18 months), and when children are 24 and 36 months old. The outcomes are expected to assess the impact of the interventions and provide new insights into the mechanisms underlying the development of vegetable acceptance, self-regulation and healthy eating patterns in infants and toddlers, as well as the prevention of overweight. The results may be used to improve current dietary advice given to parents of their young children on complementary feeding. The trial was retrospectively registered during inclusion of participants at the Netherlands National Trial Register (identifier NTR6572 ) and at ClinicalTrials.gov ( NCT03348176 ). Protocol issue date: 1 April 2018; version number 1.