A selective inhibitor of the NLRP3 inflammasome as a potential therapeutic approach for neuroprotection in a transgenic mouse model of Huntington's disease.

BACKGROUND: Huntington's disease (HD) is a neurodegenerative disorder caused by the expansion of the CAG repeat in the huntingtin (HTT) gene. When the number of CAG repeats exceeds 36, the translated expanded polyglutamine-containing HTT protein (mutant HTT [mHTT]) interferes with the normal functions of many cellular proteins and subsequently jeopardizes important cellular machineries in major types of brain cells, including neurons, astrocytes, and microglia. The NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome, which comprises NLRP3, ASC, and caspase-1, is involved in the activation of IL-1ß and IL-18 and has been implicated in various biological functions. Although the existence of the NLRP3 inflammasome in the brain has been documented, the roles of the NLRP3 inflammasome in HD remain largely uncharacterized. MCC950 is a highly selective and potent small-molecule inhibitor of NLRP3 that has been used for the treatment of several diseases such as Alzheimer's disease. However, whether MCC950 is also beneficial in HD remains unknown. Therefore, we hypothesized that MCC950 exerts beneficial effects in a transgenic mouse model of HD. METHODS: To evaluate the effects of MCC950 in HD, we used the R6/2 (B6CBA-Tg[HDexon1]62Gpb/1J) transgenic mouse model of HD, which expresses exon 1 of the human HTT gene carrying 120 ± 5 CAG repeats. Male transgenic R6/2 mice were treated daily with MCC950 (10 mg/kg of body weight; oral administration) or water for 5 weeks from the age of 7 weeks. We examined neuronal density, neuroinflammation, and mHTT aggregation in the striatum of R6/2 mice vs. their wild-type littermates. We also evaluated the motor function, body weight, and lifespan of R6/2 mice. RESULTS: Systematic administration of MCC950 to R6/2 mice suppressed the NLRP3 inflammasome, decreased IL-1ß and reactive oxygen species production, and reduced neuronal toxicity, as assessed based on increased neuronal density and upregulation of the NeuN and PSD-95 proteins. Most importantly, oral administration of MCC950 increased neuronal survival, reduced neuroinflammation, extended lifespan, and improved motor dysfunction in R6/2 mice. CONCLUSIONS: Collectively, our findings indicate that MCC950 exerts beneficial effects in a transgenic mouse model of HD and has therapeutic potential for treatment of this devastating neurodegenerative disease.

ID4 predicts poor prognosis and promotes BDNF-mediated oncogenesis of colorectal cancer.

Inhibitors of DNA binding and cell differentiation (ID) proteins regulate cellular differentiation and tumor progression. Whether ID family proteins serve as a linkage between pathological differentiation and cancer stemness in colorectal cancer is largely unknown. Here, the expression of ID4, but not other ID family proteins, was enriched in LGR5-high colon cancer stem cells. Its high expression was associated with poor pathological differentiation of colorectal tumors and shorter survival in patients. Knockdown of ID4 inhibited the growth and dissemination of colon cancer cells, while enhancing chemosensitivity. Through gene expression profiling analysis, brain-derived neurotrophic factor (BDNF) was identified as a downstream target of ID4 expression in colorectal cancer. BDNF knockdown decreased the growth and migration of colon cancer cells, and its expression enhanced dissemination, anoikis resistance and chemoresistance. ID4 silencing attenuated the epithelial-to-mesenchymal transition pattern in colon cancer cells. Gene cluster analysis revealed that ID4 and BDNF expression was clustered with mesenchymal markers and distant from epithelial genes. BDNF silencing decreased the expression of mesenchymal markers Vimentin, CDH2 and SNAI1. These findings demonstrated that ID4-BDNF signaling regulates colorectal cancer survival, with the potential to serve as a prognostic marker in colorectal cancer.

Do certified cancer centers provide more cost-effective care? A health economic analysis of colon cancer care in Germany using administrative data.

Hospital certification has become an important measure to improve cancer care quality, with the potential effect of prolonging patient survival and reducing medical spending. However, yet to be explored is the cost-effectiveness of cancer care provided in certified hospitals, considering significant additional costs incurred from certification requirements. We performed a cost-effectiveness analysis (CEA) using two colon cancer populations (N = 1909) treated in different levels of certified hospitals (CHs) vs noncertified hospitals (NCHs) from a healthcare system's perspective. We matched patient-level data of incident colon cancer cases, diagnosed between 2008 and 2013 from a large statutory health insurance in Saxony, Germany, to calculate net treatment costs by phase (initial, continuing and terminal phase). The costs were supplemented with extra costs from 31 additional services required for certification. Effectiveness measure was total survival time in life-years. Outcome of interest was incremental costs per additional life-year. The annualized net colon cancer treatment costs by phase showed a U shape with high costs in the initial (mean €26 855; 95% CI €25 058-€28 652) and the terminal phases (mean €30 096; 95% CI €26 199-€33 993). The base-case CEA results and all sensitivity analyses consistently demonstrated longer survival and lower costs for the colon cancer cohort treated in CHs vs NCHs. To conclude, we used administrative data to derive the first cost-effectiveness evidence supporting that colon cancer care delivered in the certified cancer centers in Germany improves survival outcomes and saves costs from a healthcare system's perspective. Generalization of the study results should be exercised with caution.

Evaluating key characteristics of ideal colorectal cancer screening modalities: the microsimulation approach.

BACKGROUND AND AIMS: Screening for colorectal cancer (CRC) can effectively reduce CRC incidence and mortality. Besides colonoscopy, tests for the detection of biomarkers in stool, blood, or serum, including the fecal immunochemical test (FIT), ColoGuard, Epi proColon, and PolypDx, have recently been advanced. We aimed to identify the characteristics of theoretic, highly efficient screening tests and calculated the effectiveness and cost effectiveness of available screening tests. METHODS: Using the microsimulation-based colon modeling open-source tool (CMOST), we simulated 142,501 theoretic screening tests with variable assumptions for adenoma and carcinoma sensitivity, specificity, test frequency, and adherence, and we identified highly efficient tests outperforming colonoscopy. For available screening tests, we simulated 10 replicates of a virtual population of 2 million individuals, using epidemiologic characteristics and costs assumptions of the United States. RESULTS: Highly efficient theoretic screening tests were characterized by high sensitivity for advanced adenoma and carcinoma and high patient adherence. All simulated available screening tests were effective at 100% adherence to screening and at expected real-world adherence rates. All tests were cost effective below the threshold of 100,000 U.S. dollars per life year gained. With perfect adherence, FIT was the most effective and cost-efficient intervention, whereas Epi proColon was the most effective at expected real-world adherence rates. In our sensitivity analysis, assumptions for patient adherence had the strongest impact on effectiveness of screening. CONCLUSIONS: Our microsimulation study identified characteristics of highly efficient theoretic screening tests and confirmed the effectiveness and cost-effectiveness of colonoscopy and available urine-, blood-, and stool-based tests. Better patient adherence results in superior effectiveness for CRC prevention in the whole population.

Reduction of phase error on phase-only volume-holographic disc rotation with pre-processing by phase integral.

In this paper, we present a study of observation of phase error of a volume holographic storage disc during the reading process when the disc is rotated or displaced in the theoretical calculation and the corresponding experiment. This additional phase error will dramatically decrease the bit error rate of a phase-only signal, even applying double-frequency shearing interferometry to retrieve the stored phase signal. Then we propose a novel approach to solve the problem. The stored signal is pre-processed by phase integral along the shearing direction so that applying the integral process to decode the phase signal is not necessary in the readout process. The proposed approach effectively reduces the error in phase retrieval and will be useful when applying double-frequency shearing interferometry in the readout process for volume holographic storage.

Cost-Effectiveness of Colorectal Cancer Screening Strategies-A Systematic Review.

BACKGROUND & AIMS: Widespread screening for colorectal cancer (CRC) has reduced its incidence and mortality. Previous studies investigated the economic effects of CRC screening. We performed a systematic review to provide up-to-date evidence of the cost effectiveness of CRC screening strategies by answering 3 research questions. METHODS: We searched PubMed, National Institute for Health Research Economic Evaluation Database, Social Sciences Citation Index (via the Web of Science), EconLit (American Economic Association) and 3 supplemental databases for original articles published in English from January 2010 through December 2017. All monetary values were converted to US dollars (year 2016). For all research questions, we extracted, or calculated (if necessary), per-person costs and life years (LYs) and/or quality-adjusted LYs, as well as the incremental costs per LY gained or quality-adjusted LY gained compared with the baseline strategy. A cost-saving strategy was defined as one that was less costly and equally or more effective than the baseline strategy. The net monetary benefit approach was used to answer research question 2. RESULTS: Our review comprised 33 studies (17 from Europe, 11 from North America, 4 from Asia, and 1 from Australia). Annual and biennial guaiac-based fecal occult blood tests, annual and biennial fecal immunochemical tests, colonoscopy every 10 years, and flexible sigmoidoscopy every 5 years were cost effective (even cost saving in most US models) compared to no screening. In addition, colonoscopy every 10 years was less costly and/or more effective than other common strategies in the United States. Newer strategies such as computed tomographic colonography, every 5 or 10 years, was cost effective compared with no screening. CONCLUSIONS: In an updated review, we found that common CRC screening strategies and computed tomographic colonography continued to be cost effective compared to no screening. There were discrepancies among studies from different regions, which could be associated with the model types or model assumptions.

Determinants of heterosexual men's demand for long-acting injectable pre-exposure prophylaxis (PrEP) for HIV in urban South Africa.

BACKGROUND: Heterosexual men in South Africa are a large key population to exposure to HIV, yet preferences for HIV pre-exposure prophylaxis (PrEP) among this population have not, to date, been investigated in the literature. This paper aims to explore HIV prevention preferences among heterosexual men in urban South Africa, as well as to examine the demand and characteristics of men who favour long-acting injectable (LAI) PrEP over condoms and oral PrEP. METHODS: Data were collected among 178 self-reported HIV-negative heterosexual men, who were given example products and information before being asked which they preferred. Multivariate logistic regression was used to analyse which characteristics were associated with product choice. RESULTS: 48% (n = 85) of participants preferred LAI PrEP, while 33% (n = 58) and 20% (n = 35) chose oral PrEP and condoms respectively. Having children (marginal effect = 0.22; 95% CI [0.01, 0.44]) or having higher risk attitude scores (marginal effect = 0.03; 95% CI [0.01, 0.06]) was significantly associated with a choice of LAI PrEP, while those who had unprotected anal intercourse (marginal effect = - 0.42; 95% CI [- 0.57, - 0.27]) and those who were concerned with protection against other sexually transmitted infections over HIV (marginal effect = - 0.42; 95% CI [- 0.60, - 0.24]) appeared less likely to prefer LAI PrEP. CONCLUSIONS: The results suggested a relatively high demand and theoretical acceptability for LAI PrEP among heterosexual men in urban South Africa, but there appeared to be fewer distinct predictors for the willingness to use LAI PrEP compared to studies conducted among gay and bisexual men and women. Nevertheless, the findings contribute to the mapping of the demand and determinants of heterosexual men's preferences for novel antiretroviral-based prevention in sub-Saharan Africa, and the data could aid in the differentiated design of future HIV prevention strategies using LAI PrEP in conjunction with other methods.

[The health economics of cancer screening in Germany: Which population-based interventions are cost-effective?] / Gesundheitsökonomie der Krebsfrüherkennung in Deutschland: Welche Interventionen sind kosteneffektiv bei bevölkerungsweiter Umsetzung?

Only a small proportion of German health expenditure is spent on prevention and early detection (screening). The rationale for screening is to identify persons with disease precursors or at the early stage of diseases when they are still asymptomatic, in order to decrease disease-specific morbidity and mortality. In Germany, the economic evidence is one of the evaluation criteria for screening measures, which, among other things, takes into account the additional cost per additional case detected or per case-related event avoided, as well as a cost-benefit balance.For this purpose, cost-effectiveness analyses, which report marginal or incremental cost effectiveness ratios, comparing a measure with its appropriate alternatives, may be a useful tool. Their application requires a defensible benchmark (threshold) for cost effectiveness and a supplementary analysis of the necessary infrastructure and the budgetary impact associated with program implementation. Also (albeit not only) because of the usually long time required to observe the clinical outcomes of a screening measure, the economic evaluation of such programs regularly involves the application of decision analytic simulation models. With regard to cancer screening programs, the available models indicate an excellent cost-benefit ratio for the fecal occult blood test and colonoscopy for colorectal cancer screening and, similarly, for the use of mammography for breast cancer screening. On the other hand, the economic evidence in favor of low-dose computed tomography for lung cancer screening does not yet appear sufficiently strong, and the currently available health economic evidence does not support the use of PSA testing for prostate screening.

One-shot and aberration-tolerable homodyne detection for holographic storage readout through double-frequency grating-based lateral shearing interferometry.

A simple method to decode the stored phase signal of volume holographic data storage with adequate wave aberration tolerance is highly demanded. We proposed and demonstrated a one-shot scheme to decode a binary-phase encoding signal through double-frequency-grating based shearing interferometry (DFGSI). The lateral shearing amount is dependent on the focal length of the collimated lens and the frequency difference between the gratings. Diffracted waves with phase encoding were successfully decoded through experimentation. An optical model for the DFGSI was built to analyze phase-error induction and phase-difference control by shifting the double-frequency grating longitudinally and laterally, respectively. The optical model was demonstrated experimentally. Finally, a high aberration tolerance of the DFGSI was demonstrated using the optical model.

Would initiating colorectal cancer screening from age of 45 be cost-effective in Germany? An individual-level simulation analysis.

Background: Colorectal cancer (CRC) screening has been shown to be effective and cost-saving. However, the trend of rising incidence of early-onset CRC challenges the current national screening program solely for people ≥50 years in Germany, where extending the screening to those 45-49 years might be justified. This study aims to evaluate the cost-effectiveness of CRC screening strategies starting at 45 years in Germany. Method: DECAS, an individual-level simulation model accounting for both adenoma and serrated pathways of CRC development and validated with German CRC epidemiology and screening effects, was used for the cost-effectiveness analysis. Four CRC screening strategies starting at age 45, including 10-yearly colonoscopy (COL), annual/biennial fecal immunochemical test (FIT), or the combination of the two, were compared with the current screening offer starting at age 50 years in Germany. Three adherence scenarios were considered: perfect adherence, current adherence, and high screening adherence. For each strategy, a cohort of 100,000 individuals with average CRC risk was simulated from age 20 until 90 or death. Outcomes included CRC cases averted, prevented death, quality-adjusted life-years gained (QALYG), and total incremental costs considering both CRC treatment and screening costs. A 3% discount rate was applied and costs were in 2023 Euro. Result: Initiating 10-yearly colonoscopy-only or combined FIT + COL strategies at age 45 resulted in incremental gains of 7-28 QALYs with incremental costs of €28,360-€71,759 per 1,000 individuals, compared to the current strategy. The ICER varied from €1,029 to €9,763 per QALYG, and the additional number needed for colonoscopy ranged from 129 to 885 per 1,000 individuals. Among the alternatives, a three times colonoscopy strategy starting at 45 years of age proves to be the most effective, while the FIT-only strategy was dominated by the currently implemented strategy. The findings remained consistent across probabilistic sensitivity analyses. Conclusion: The cost-effectiveness findings support initiating CRC screening at age 45 with either colonoscopy alone or combined with FIT, demonstrating substantial gains in quality-adjusted life-years with a modest increase in costs. Our findings emphasize the importance of implementing CRC screening 5 years earlier than the current practice to achieve more significant health and economic benefits.

Optimal timing of a colonoscopy screening schedule depends on adenoma detection, adenoma risk, adherence to screening and the screening objective: A microsimulation study.

Colonoscopy-based screening provides protection against colorectal cancer (CRC), but the optimal starting age and time intervals of screening colonoscopies are unknown. We aimed to determine an optimal screening schedule for the US population and its dependencies on the objective of screening (life years gained or incidence, mortality, or cost reduction) and the setting in which screening is performed. We used our established open-source microsimulation model CMOST to calculate optimized colonoscopy schedules with one, two, three or four screening colonoscopies between 20 and 90 years of age. A single screening colonoscopy was most effective in reducing life years lost from CRC when performed at 55 years of age. Two, three and four screening colonoscopy schedules saved a maximum number of life years when performed between 49-64 years; 44-69 years; and 40-72 years; respectively. However, for maximum incidence and mortality reduction, screening colonoscopies needed to be scheduled 4-8 years later in life. The optimum was also influenced by adenoma detection efficiency with lower values for these parameters favoring a later starting age of screening. Low adherence to screening consistently favored a later start and an earlier end of screening. In a personalized approach, optimal screening would start earlier for high-risk patients and later for low-risk individuals. In conclusion, our microsimulation-based approach supports colonoscopy screening schedule between 45 and 75 years of age but the precise timing depends on the objective of screening, as well as assumptions regarding individual CRC risk, efficiency of adenoma detection during colonoscopy and adherence to screening.

Color gamut characteristics of diffractive-light guides of near-eye augmented reality glasses.

We delve into the distinctive color gamut characteristics resulting from color dispersion of surface relief grating (SRG) and wavelength degeneracy of volume holographic optical element (VHOE) in a diffractive light guide. While a laser-like spectrum achieves an impressive 194% sRGB color gamut for both cases, it proves unsuitable for VHOE light guides due to limitations in breaking the field of view (FOV) of the display. Conversely, a broad-band light source, such as LEDs, offers continuous FOV but reduces the common color gamut to 50% sRGB. We then present a newly designed VHOE light guide capable of achieving the common color gamut of 130% sRGB using two multiplexed holograms of each color, closely matching the 133% sRGB achieved by an SRG light guide. This article presents the first theoretical methodology to elucidate color performance of diffractive light guides utilizing VHOEs with holographic multiplexing, affirming their suitability for crafting high-quality near-eye display.

Modeling the Natural History and Screening Effects of Colorectal Cancer Using Both Adenoma and Serrated Neoplasia Pathways: The Development, Calibration, and Validation of a Discrete Event Simulation Model.

Background. Existing colorectal cancer (CRC) screening models mostly focus on the adenoma pathway of CRC development, overlooking the serrated neoplasia pathway, which might result in overly optimistic screening predictions. In addition, Bayesian inference methods have not been widely used for model calibration. We aimed to develop a CRC screening model accounting for both pathways, calibrate it with approximate Bayesian computation (ABC) methods, and validate it with large CRC screening trials. Methods. A discrete event simulation (DES) of the CRC natural history (DECAS) was constructed using the adenoma and serrated pathways in R software. The model simulates CRC-related events in a specific birth cohort through various natural history states. Calibration took advantage of 74 prevalence data points from the German screening colonoscopy program of 5.2 million average-risk participants using an ABC method. CRC incidence outputs from DECAS were validated with the German national cancer registry data; screening effects were validated using 17-y data from the UK Flexible Sigmoidoscopy Screening sigmoidoscopy trial and a German screening colonoscopy cohort study. Results. The Bayesian calibration rendered 1,000 sets of posterior parameter samples. With the calibrated parameters, the observed age- and sex-specific CRC prevalences from the German registries were within the 95% DECAS-predicted intervals. Regarding screening effects, DECAS predicted a 41% (95% intervals 30%-51%) and 62% (95% intervals 55%-68%) reduction in 17-y cumulative CRC mortality for a single screening sigmoidoscopy and colonoscopy, respectively, falling within 95% confidence intervals reported in the 2 clinical studies used for validation. Conclusions. We presented DECAS, the first Bayesian-calibrated DES model for CRC natural history and screening, accounting for 2 CRC tumorigenesis pathways. The validated model can serve as a valid tool to evaluate the (cost-)effectiveness of CRC screening strategies. Highlights: This article presents a new discrete event simulation model, DECAS, which models both adenoma-carcinoma and serrated neoplasia pathways for colorectal cancer (CRC) development and CRC screening effects.DECAS is calibrated based on a Bayesian inference method using the data from German screening colonoscopy program, which consists of more than 5 million first-time average-risk participants aged 55 years and older in 2003 to 2014.DECAS is flexible for evaluating various CRC screening strategies and can differentiate screening effects in different parts of the colon.DECAS is validated with large screening sigmoidoscopy and colonoscopy clinical study data and can be further used to evaluate the (cost-)effectiveness of German colorectal cancer screening strategies.

Budget impact of introducing once-every-6-months paliperidone palmitate in US health care plans.

BACKGROUND: In the United States, most patients with schizophrenia have Medicaid coverage. Antipsychotic treatments are the cornerstone of schizophrenia management; most patients are treated with daily oral antipsychotics but struggle with medication adherence. Evidence suggests that medication adherence is inversely correlated with dosing frequency. Once-monthly paliperidone palmitate (PP) has been demonstrated to improve adherence compared with oral antipsychotics; transitioning to once-every-3-months PP (PP3M) further improved adherence. In 2021, once-every-6-months PP (PP6M) was approved by the US Food and Drug Administration to provide even longer between-dose intervals. Public health stakeholders who aim to improve medication adherence are interested in understanding how introducing PP6M to the formulary will impact the budget. OBJECTIVE: To evaluate the budget impact of introducing PP6M to the formulary from the perspectives of a hypothetical US multistate health care payer and state Medicaid programs using California, Georgia, and Ohio as examples. METHODS: The budget impact model was developed from a payer perspective, comparing the reference scenario (without PP6M in the market) with a new scenario (with PP6M). The study population included patients with schizophrenia who were eligible to receive PP6M. Market shares were assigned to the reference and new market scenarios. Efficacy was measured by the relative risk of relapse while receiving treatment. Adherence effects were included in the model and affected costs of treatment and relapse rates. A deterministic 1-way sensitivity analysis was performed. RESULTS: Base-case results for a multistate payer with 1 million members demonstrate that adding PP6M to the market results in total incremental plan-level costs ranging from $7,747 in year 1 to $11,501 in year 5. Increased drug costs were offset by administration and relapse cost savings ($105 and $881 in year 5, respectively). The average incremental cost per treated patient per year was stable at $180.06 for each year, and the incremental cost per member per month stayed below $0.01 for each year. The results of the model from the state-level Medicaid scenarios are broadly similar to those of the multistate base-case perspective. The 1-way sensitivity analysis demonstrated the model is most sensitive to the per-package costs of PP6M and PP3M, along with the proportion of patients fully adherent with PP3M. CONCLUSIONS: The budget impact of introducing PP6M as a treatment option is minimal. With the expected cost offsets from reduced administration and relapse costs due to adherence benefits, these results suggest that PP6M can be a viable treatment option from a clinical and a budgetary perspective. DISCLOSURES: This study was funded by Janssen Scientific Affairs, LLC. The study sponsor provided funds to Xcenda and ApotheCom for medical writing, editorial support, and submission of the manuscript. Hilary Phelps was an employee of Janssen Global Services, LLC, at the time of the development and finalization of the manuscript. Alex Keenan is an employee of Janssen Global Services, LLC, and holds stock in Johnson & Johnson, Inc. Dee Lin and Carmela Benson are employees of Janssen Scientific Affairs, LLC, and hold stock in Johnson & Johnson, Inc. Aditya Raju was an employee of Xcenda at the time of the development and finalization of the manuscript, and Danmeng Huang is an employee of Xcenda, a health care consulting firm that was contracted by Janssen Scientific Affairs, LLC. Chih-Yuan Cheng is an employee of Janssen NV.

Reply to Standaert, B. Comment on "Postma et al. Predicted Public Health and Economic Impact of Respiratory Syncytial Virus Vaccination with Variable Duration of Protection for Adults ≥60 Years in Belgium".

We have read the commentary from Baudouin Standaert [...].

Predicted Public Health and Economic Impact of Respiratory Syncytial Virus Vaccination with Variable Duration of Protection for Adults ≥60 Years in Belgium.

Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infection (ARI) in older adults. This study used a static, cohort-based decision-tree model to estimate the public health and economic impact of vaccination against RSV in Belgians aged ≥60 years compared with no vaccination for different vaccine duration of protection profiles from a healthcare payer perspective. Three vaccine protection durations were compared (1, 3, and 5 years), and several sensitivity and scenario analyses were performed. Results showed that an RSV vaccine with a 3-year duration of protection would prevent 154,728 symptomatic RSV-ARI cases, 3688 hospitalizations, and 502 deaths over three years compared to no vaccination in older adults and would save EUR 35,982,857 in direct medical costs in Belgium. The number needed to vaccinate to prevent one RSV-ARI case was 11 for the 3-year duration profile, while it was 28 and 8 for the 1- and 5-year vaccine duration profiles, respectively. The model was generally robust in sensitivity analyses varying key input values. This study suggested that vaccination could substantially decrease the public health and economic burden of RSV in adults ≥60 years in Belgium, with benefits increasing with a longer duration of vaccine protection.

Method of compensating for pixel migration in volume holographic optical disc (VHOD).

Volume holographic optical disc (VHOD) technology is simpler than the angular multiplexing holographic system. However, disc rotation usually causes pixel migration, thus reducing signal quality. This study proposes a special geometrical arrangement to counteract pixel migration. Using paraxial approximation analysis, an optimal geometrical distance ratio, K, is calculated to compensate for pixel migration and improve image quality during disc rotation. The results of approximation analysis are confirmed by both simulation and experimental results.

Survival and comorbidities in lung cancer patients: Evidence from administrative claims data in Germany.

Lung cancer is the most common cancer type worldwide and has the highest and second highest mortality rate for men and women respectively in Germany. Yet, the role of comorbid illnesses in lung cancer patient prognosis is still debated. We analyzed administrative claims data from one of the largest statutory health insurance (SHI) funds in Germany, covering close to 9 million people (11% of the national population); observation period was from 2005 to 2019. Lung cancer patients and their concomitant diseases were identified by ICD-10-GM codes. Comorbidities were classified according to the Charlson Comorbidity Index (CCI). Incidence, comorbidity prevalence and survival are estimated considering sex, age at diagnosis, and place of residence. Kaplan Meier curves with 95% confidence intervals were built in relation to common comorbidities. We identified 70,698 lung cancer incident cases in the sample. Incidence and survival figures are comparable to official statistics in Germany. Most prevalent comorbidities are chronic obstructive pulmonary disease (COPD) (36.7%), followed by peripheral vascular disease (PVD) (18.7%), diabetes without chronic complications (17.4%), congestive heart failure (CHF) (16.5%) and renal disease (14.7%). Relative to overall survival, lung cancer patients with CHF, cerebrovascular disease (CEVD) and renal disease are associated with largest drops in survival probabilities (9% or higher), while those with PVD and diabetes without chronic complications with moderate drops (7% or lower). The study showed a negative association between survival and most common comorbidities among lung cancer patients, based on a large sample for Germany. Further research needs to explore the individual effect of comorbidities disentangled from that of other patient characteristics such as cancer stage and histology.

How Much Does It Cost to Research and Develop a New Drug? A Systematic Review and Assessment.

BACKGROUND: Debate over the viability of the current commercial research and development (R&D) model is ongoing. A controversial theme is the cost of bringing a new molecular entity (NME) to market. OBJECTIVE: Our aim was to evaluate the range and suitability of published R&D cost estimates as to the degree to which they represent the actual costs of industry. METHODS: We provided a systematic literature review based on articles found in the Pubmed, Embase and EconLit electronic databases, and in a previously published review. Articles published before March 2020 that estimated the total R&D costs were included (22 articles with 45 unique cost estimates). We included only literature in which the methods used to collect the information and to estimate the R&D costs were clearly described; therefore, three reports were excluded. We extracted average pre-launch R&D costs per NME and converted the values to 2019 US dollars (US$) using the gross domestic product (GDP) price deflator. We appraised the suitability of the R&D estimated costs by using a scoring system that captures three domains: (1) how success rates and development time used for cost estimation were obtained; (2) whether the study considered potential sources contributing to the variation in R&D costs; and (3) what the components of the cost estimation were. RESULTS: Estimates of total average capitalized pre-launch R&D costs varied widely, ranging from $161 million to $4.54 billion (2019 US$). Therapeutic area-specific estimates were highest for anticancer drugs (between $944 million and $4.54 billion). Our analysis identified a trend of increasing R&D costs per NME over time but did not reveal a relation between cost estimates and study ranking when the suitability scores were assessed. We found no evidence of an increase in suitability scores over time. CONCLUSION: There is no universally correct answer regarding how much it costs, on average, to research and develop an NME. Future studies should explicitly address previously neglected variables, which likely explain some variability in estimates, and consider the trade-off between the transparency and public accessibility of data and their specificity. Use of our proposed suitability scoring system may assist in addressing such issues.

The Effect of Feeding Restriction on the Microbiota and Metabolome Response in Late-Phase Laying Hens.

This study investigated cecal bacterial community profile, cecal and serum metabolites, and its biosynthesis pathway in late-phase laying hens during 6 weeks feeding restriction (FR), using 16S rDNA as gene sequencing and non-targeted LC-MS/MS as metabolomics approach. We used three groups (ad libitum, FR20, and FR40). FR can reduce excessive fat in late-phase laying hens, while egg production rate is not affected, except for the FR40 group. In phylum level, FR20 had more population of Bacteriodetes and Firmicutes amongst groups. The same result is at genus level, FR20 were higher of the predominant genus (Bacteroides and Rikenellaceae_RC9_gut_group). Both of FR20 and FR40 reduced Proteobacteria as potential pathogenic bacteria. Non-targeted metabolomic analysis revealed that FR20 modified 20 metabolites in cecal and 10 metabolites in serum of laying hens, whereas 48 cecal metabolites and 31 serum metabolites has revealed in FR40. KEGG assay showed FR20 and FR40 upregulated lipid, carbohydrate, amino acid, nucleic acid pathway, and FR40 modified steroid metabolism in cecal analysis. In serum, only FR40 modified lipid, amino acid pathway, and carbohydrate biosynthesis were shown. This study showed that FR during late-phase laying hens altered the microbiome composition, modified metabolites profile and biosynthesis of the cecal as well as serum.