Recessively Inherited Deficiency of Secreted WFDC2 (HE4) Causes Nasal Polyposis and Bronchiectasis.

Rationale: Bronchiectasis is a pathological dilatation of the bronchi in the respiratory airways associated with environmental or genetic causes (e.g., cystic fibrosis, primary ciliary dyskinesia, and primary immunodeficiency disorders), but most cases remain idiopathic. Objectives: To identify novel genetic defects in unsolved cases of bronchiectasis presenting with severe rhinosinusitis, nasal polyposis, and pulmonary Pseudomonas aeruginosa infection. Methods: DNA was analyzed by next-generation or targeted Sanger sequencing. RNA was analyzed by quantitative PCR and single-cell RNA sequencing. Patient-derived cells, cell cultures, and secretions (mucus, saliva, seminal fluid) were analyzed by Western blotting and immunofluorescence microscopy, and mucociliary activity was measured. Blood serum was analyzed by electrochemiluminescence immunoassay. Protein structure and proteomic analyses were used to assess the impact of a disease-causing founder variant. Measurements and Main Results: We identified biallelic pathogenic variants in WAP four-disulfide core domain 2 (WFDC2) in 11 individuals from 10 unrelated families originating from the United States, Europe, Asia, and Africa. Expression of WFDC2 was detected predominantly in secretory cells of control airway epithelium and also in submucosal glands. We demonstrate that WFDC2 is below the limit of detection in blood serum and hardly detectable in samples of saliva, seminal fluid, and airway surface liquid from WFDC2-deficient individuals. Computer simulations and deglycosylation assays indicate that the disease-causing founder variant p.Cys49Arg structurally hampers glycosylation and, thus, secretion of mature WFDC2. Conclusions: WFDC2 dysfunction defines a novel molecular etiology of bronchiectasis characterized by the deficiency of a secreted component of the airways. A commercially available blood test combined with genetic testing allows its diagnosis.

Pathogenic variants in CFAP46, CFAP54, CFAP74, and CFAP221 cause Primary Ciliary Dyskinesia with a defective C1d projection of the central apparatus.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare genetic disorder caused by insufficient mucociliary clearance leading to chronic airway infections. The diagnostic guideline of the European Respiratory Society (ERS) primarily recommends the evaluation of the clinical history (e. g. by the PICADAR prediction tool), nasal nitric oxide (nNO) production rate measurements, high-speed videomicroscopy analysis (HSVMA) of ciliary beating, and the assessment of ciliary axonemes via transmission electron microscopy (TEM). Genetic testing can be implemented as a last step. QUESTION: In this study, we aimed to characterise PCD with a defective C1d projection of the ciliary central apparatus (CA) and evaluated the applicability of the ERS diagnostic guideline to this PCD type. METHODS: Using a high-throughput sequencing approach of genes encoding C1d components, we identified pathogenic variants in the novel PCD genes CFAP46 and CFAP54, and the known PCD gene CFAP221. To fully assess this PCD type, we also analysed individuals with pathogenic variants in CFAP74. RESULTS: Careful evaluation revealed that C1d-defective PCD is associated with normal situs composition, normal nNO-production rates, normal ciliary ultrastructure by TEM, and normal ciliary beating by HSVMA. Despite chronic respiratory disease, PICADAR does not reliably detect this PCD type. However, we could show by in-vitro ciliary transport assays that affected individuals exhibit insufficient ciliary clearance. CONCLUSIONS: Overall, this study extends the spectrum of PCD genes and highlights that C1d-defective PCD individuals elude diagnosis in the current diagnostic algorithm. To enable diagnosis, genetic testing should be prioritised in future diagnostic guidelines.

A range of 30-62% of functioning multiciliated airway cells is sufficient to maintain ciliary airway clearance.

BACKGROUND: Primary ciliary dyskinesia is a genetic disorder caused by aberrant motile cilia function that results in defective ciliary airway clearance and subsequently leads to recurrent airway infections and bronchiectasis. We aimed to determine: how many functional multiciliated airway cells are sufficient to maintain ciliary airway clearance? METHODS: To answer this question we exploited the molecular defects of the X-linked recessive primary ciliary dyskinesia variant caused by pathogenic variants in DNAAF6 (PIH1D3), characterised by immotile cilia in affected males. We carefully analysed the clinical phenotype and molecular defect (using immunofluorescence and transmission electron microscopy) and performed in vitro studies (particle tracking in air-liquid interface cultures) and in vivo studies (radiolabelled tracer studies) to assess ciliary clearance of respiratory cells from female individuals with heterozygous and male individuals with hemizygous pathogenic DNAAF6 variants. RESULTS: Primary ciliary dyskinesia male individuals with hemizygous pathogenic DNAAF6 variants displayed exclusively immotile cilia, absence of ciliary clearance and severe primary ciliary dyskinesia symptoms. Owing to random or skewed X-chromosome inactivation in six female carriers with heterozygous pathogenic DNAAF6 variants, 54.3±10% (range 38-70%) of multiciliated cells were defective. Nevertheless, in vitro and in vivo assessment of the ciliary airway clearance was normal or slightly abnormal. Consistently, heterozygous female individuals showed no or only mild respiratory symptoms. CONCLUSIONS: Our findings indicate that having 30-62% of multiciliated respiratory cells functioning can generate either normal or slightly reduced ciliary clearance. Because heterozygous female carriers displayed either no or subtle respiratory symptoms, complete correction of 30% of cells by precision medicine could improve ciliary airway clearance in individuals with primary ciliary dyskinesia, as well as clinical symptoms.

Immunofluorescence analyses of respiratory epithelial cells aid the diagnosis of nephronophthisis.

BACKGROUND: Nephronophthisis (NPH) comprises a heterogeneous group of inherited renal ciliopathies clinically characterized by progressive kidney failure. So far, definite diagnosis is based on molecular testing only. Here, we studied the feasibility of NPHP1 and NPHP4 immunostaining of nasal epithelial cells to secure and accelerate the diagnosis of NPH. METHODS: Samples of 86 individuals with genetically determined renal ciliopathies were analyzed for NPHP1 localization using immunofluorescence microscopy (IF). A sub-cohort of 35 individuals was also analyzed for NPHP4 localization. Western blotting was performed to confirm IF results. RESULTS: NPHP1 and NPHP4 were both absent in all individuals with disease-causing NPHP1 variants including one with a homozygous missense variant (c.1027G > A; p.Gly343Arg) formerly classified as a "variant of unknown significance." In individuals with an NPHP4 genotype, we observed a complete absence of NPHP4 while NPHP1 was severely reduced. IF results were confirmed by immunoblotting. Variants in other genes related to renal ciliopathies did not show any impact on NPHP1/NPHP4 expression. Aberrant immunostaining in two genetically unsolved individuals gave rise for a further genetic workup resulting in a genetic diagnosis for both with disease-causing variants in NPHP1 and NPHP4, respectively. CONCLUSIONS: IF of patient-derived respiratory epithelial cells may help to secure and accelerate the diagnosis of nephronophthisis-both by verifying inconclusive genetic results and by stratifying genetic diagnostic approaches. Furthermore, we provide in vivo evidence for the interaction of NPHP1 and NPHP4 in a functional module.

Biallelic DAW1 variants cause a motile ciliopathy characterized by laterality defects and subtle ciliary beating abnormalities.

PURPOSE: The clinical spectrum of motile ciliopathies includes laterality defects, hydrocephalus, and infertility as well as primary ciliary dyskinesia when impaired mucociliary clearance results in otosinopulmonary disease. Importantly, approximately 30% of patients with primary ciliary dyskinesia lack a genetic diagnosis. METHODS: Clinical, genomic, biochemical, and functional studies were performed alongside in vivo modeling of DAW1 variants. RESULTS: In this study, we identified biallelic DAW1 variants associated with laterality defects and respiratory symptoms compatible with motile cilia dysfunction. In early mouse embryos, we showed that Daw1 expression is limited to distal, motile ciliated cells of the node, consistent with a role in left-right patterning. daw1 mutant zebrafish exhibited reduced cilia motility and left-right patterning defects, including cardiac looping abnormalities. Importantly, these defects were rescued by wild-type, but not mutant daw1, gene expression. In addition, pathogenic DAW1 missense variants displayed reduced protein stability, whereas DAW1 loss-of-function was associated with distal type 2 outer dynein arm assembly defects involving axonemal respiratory cilia proteins, explaining the reduced cilia-induced fluid flow in particle tracking velocimetry experiments. CONCLUSION: Our data define biallelic DAW1 variants as a cause of human motile ciliopathy and determine that the disease mechanism involves motile cilia dysfunction, explaining the ciliary beating defects observed in affected individuals.

Layering of magnetic nanoparticles at amorphous magnetic templates with perpendicular anisotropy.

We reveal the assembly of magnetite nanoparticles of sizes 5 nm, 15 nm and 25 nm from dilute water-based ferrofluids onto an amorphous magnetic template with out-of-plane anisotropy. From neutron reflectometry experiments we extract density profiles and show that the particles self-assemble into layers at the magnetic surface. The layers are extremely stable against cleaning and rinsing of the substrate. The density of the layers is determined by and increases with the remanent magnetic moment of the particles.

Long-Term Monitoring of the Internal Energy Distribution of Isolated Cluster Systems.

A method is presented to monitor the internal energy distribution of cluster anions via delayed electron detachment by pulsed photoexcitation and demonstrated on Co_{4}^{-} in an electrostatic ion beam trap. In a cryogenic operation, we calibrate the detachment delay to internal energy. By laser frequency scans, at room temperature, we reconstruct the time-dependent internal energy distribution of the clusters. The mean energies of ensembles from a cold and a hot ion source both approach thermal equilibrium. Our data yield a radiative emission law and the absorptivity of the cluster for thermal radiation.

A Unifying Hypothesis for the Genome Dynamics Proposed to Underlie Neuropsychiatric Phenotypes.

The sheer number of gene variants and the extent of the observed clinical and molecular heterogeneity recorded in neuropsychiatric disorders (NPDs) could be due to the magnified downstream effects initiated by a smaller group of genomic higher-order alterations in response to endogenous or environmental stress. Chromosomal common fragile sites (CFS) are functionally linked with microRNAs, gene copy number variants (CNVs), sub-microscopic deletions and duplications of DNA, rare single-nucleotide variants (SNVs/SNPs), and small insertions/deletions (indels), as well as chromosomal translocations, gene duplications, altered methylation, microRNA and L1 transposon activity, and 3-D chromosomal topology characteristics. These genomic structural features have been linked with various NPDs in mostly isolated reports and have usually only been viewed as areas harboring potential candidate genes of interest. The suggestion to use a higher level entry point (the 'fragilome' and associated features) activated by a central mechanism ('stress') for studying NPD genetics has the potential to unify the existing vast number of different observations in this field. This approach may explain the continuum of gene findings distributed between affected and unaffected individuals, the clustering of NPD phenotypes and overlapping comorbidities, the extensive clinical and molecular heterogeneity, and the association with certain other medical disorders.

Modeling Zero-inflated Count Data Using Generalized Poisson and Ordinal Logistic Regression Models in Medical Research.

Objectives: In medical research, the study's design and statistical methods are pivotal, as they guide interpretation and conclusion. Selecting appropriate statistical models hinges on the distribution of the outcome measure. Count data, frequently used in medical research, often exhibit over-dispersion or zero inflation. Occasionally, count data are considered ordinal (with a maximum outcome value of 5), and this calls for the application of ordinal regression models. Various models exist for analyzing over-dispersed data such as negative binomial, generalized Poisson (GP), and ordinal regression model. This study aims to examine whether the GP model is a superior alternative to the ordinal logistic regression (OLR) model, specifically in the context of zero-inflated Poisson models using both simulated and real-time data. Methods: Simulated data were generated with varied estimates of regression coefficients, sample sizes, and various proportions of zeros. The GP and OLR models were compared using fit statistics. Additionally, comparisons were made using real-time datasets. Results: The simulated results consistently revealed lower bias and mean squared error values in the GP model compared to the OLR model. The same trend was observed in real-time datasets, with the GP model consistently demonstrating lower standard errors. Except when the sample size was 1000 and the proportions of zeros were 30% and 40%, the Bayesian information criterion consistently favored the GP model over the OLR model. Conclusions: This study establishes that the proposed GP model offers a more advantageous alternative to the OLR model. Moreover, the GP model facilitates easier modeling and interpretation when compared to the OLR model.

Effects of Myofascial Release Techniques on Joint Range of Motion of Athletes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Although myofascial release techniques (MRTs) are commonly used to improve athletes' range of motion (ROM), the effectiveness of MRTs may vary depending on the specific method performed. This systematic review and meta-analysis aimed to evaluate the effects of MRTs on the ROM performance of athletes. (2) Methods: The electronic databases of Cochrane Library, PubMed, Scopus, and Web of Science were searched to identify relevant articles published up to June 2023. This study utilized the PRISMA guidelines, and four databases were searched. The methodological quality of the studies was assessed using the PEDro scale, and the certainty of evidence was reported using the GRADE scale. The overall effect size was calculated using the robust variance estimator, and subgroup analyses were conducted using the Hotelling Zhang test. (3) Ten studies met the inclusion criteria. The overall effect size results indicated that the myofascial release intervention had a moderate effect on ROM performance in athletes when compared to the active or passive control groups. (4) Conclusions: Alternative MRTs, such as myofascial trigger point therapy, can further improve the ROM performance of athletes. Gender, duration of intervention, and joint type may have a moderating effect on the effectiveness of MRTs.

Exact correction factor for estimating the OR in the presence of sparse data with a zero cell in 2 × 2 tables.

In case-control studies, odds ratios (OR) are calculated from 2 × 2 tables and in some instances, we observe small cell counts or zero counts in one of the cells. The corrections to calculate the ORs in the presence of empty cells are available in literature. Some of these include Yates continuity correction and Agresti and Coull correction. However, the available methods provided different corrections and the situations where each could be applied are not very apparent. Therefore, the current research proposes an iterative algorithm of estimating an exact (optimum) correction factor for the respective sample size. This was evaluated by simulating data with varying proportions and sample sizes. The estimated correction factor was considered after obtaining the bias, standard error of odds ratio, root mean square error and the coverage probability. Also, we have presented a linear function to identify the exact correction factor using sample size and proportion.

Unveiling the local structure of the amorphous metal [Formula: see text] combining first-principles-based simulations and modelling of EXAFS spectra.

Amorphous alloys exhibit useful properties such as the excellent soft magnetic behaviour of Fe-based metallic glasses. The detailed structure of amorphous [Formula: see text] with x = 0.07, 0.10, and 0.20 is in this work explored through a synergetic combination of atomistic simulations and experimental characterisation. Thin-film samples were investigated using X-ray diffraction and extended X-ray absorption fine structure (EXAFS), while the corresponding atomic structures were simulated using an efficient first-principles-based method called stochastic quenching (SQ). The simulated local atomic arrangements are investigated by constructing the radial- and angular-distribution functions, as well as by Voronoi tesselation. The radial distribution functions are then used to construct a model to fit simultaneously the experimental EXAFS data of multiple samples with different compositions, creating a simple yet accurate description of the atomic structures valid for any composition in the range x = 0.07 to 0.20, using a minimal number of free parameters. This approach significantly improves the accuracy of the fitted parameters and allows us to relate the compositional dependence of the amorphous structures with the magnetic properties. The proposed EXAFS fitting process can be generalised to other amorphous systems, contributing to the understanding of structure-property relationships and the development of amorphous alloys with tailored functional properties.

The Relationship between Magnetic Resonance Imaging and Functional Tests Assessment in Patients with Lumbar Disk Hernia.

Although magnetic resonance imaging (MRI) findings are the gold standard for diagnosing herniated discs, there are many limitations to accessing MRI scanning devices in practice. This study aimed to evaluate the relationship between functional tests (the visual analog scale (VAS), the SLUMP test, the Sciatica Bothersomeness Index (SBI), the Oswestry Disability Index (ODI), and the LASEGUE test and MRI findings (LSA, IVDH L4-L5, IVDH L5-S1, DHS L4-L5, and DHS L5-S1) in patients diagnosed with disc herniation. Seventy-eight patients who met the inclusion criteria participated in the study. Radiologists and neurologists evaluated patients with disc herniation. After the disc hernia diagnosis, the patients were referred to a physical therapist for conservative management of the disk hernia. The physical therapists assessed the pain level and performed functional tests on patients. All statistical analyses were performed using R (Core Team) software. The correlation between the measured variables was conducted using the Pearson and Spearman tests. The study results indicated statistically significant correlations between DHS L4-L5 vertebral level and functional tests (VAS: r = 0.49, p = 0.00; SBI: r = 0.44, p = 0.00; ODI: r = 0.49, p = 0.00; LASEGUE: r = -0.48, p = 0.00; SLUMP: r = 0.50, p = 0.00). In conclusion, physiotherapists may prefer functional tests to diagnose the herniated disc, and these functional tests may contribute to performing evidence-based assessments.

Effectiveness of Interventions Aimed at Changing Movement Patterns in People With Patellofemoral Pain: A Systematic Review With Network Meta-analysis.

OBJECTIVE: To summarize the effectiveness of interventions for changing movement during weight-bearing functional tasks in people with patellofemoral pain (PFP). DESIGN: Systematic review with network meta-analysis (NMA). LITERATURE SEARCH: Medline, Embase, CINAHL, SPORTDiscus, and Cochrane Library were searched from inception up to May 2023. STUDY SELECTION CRITERIA: Randomized controlled trials involving people with PFP and nonsurgical, nonpharmacological interventions on task kinematics were included. DATA SYNTHESIS: NMA was conducted for frontal knee movement data, and pairwise meta-analysis was used to pool data when NMA was not possible. Reduced movements were those changes that indicated movements occurring with less amplitude. The GRADE approach was used to grade the certainty of the evidence. RESULTS: Thirty-seven trials were included (n = 1235 participants). Combining knee/hip exercises with internal feedback had the strongest effect on reducing frontal knee movements (standardized mean difference [SMD] from NMA = -2.66; GRADE: moderate evidence). On pairwise comparisons, the same combination of interventions reduced frontal hip movements (SMD = -0.47; GRADE: moderate evidence) and increased sagittal knee movements (SMD = 1.03; GRADE: moderate evidence), with no effects on sagittal hip movements (GRADE: very low evidence), compared to knee/hip exercises alone. There was no effect for single applications of braces on the frontal knee movement (GRADE: very low evidence) and taping on movements of the knee, hip, and ankle (GRADE: very low to low evidence) compared to no intervention. CONCLUSION: Knee/hip exercises combined with internal feedback techniques may change knee and hip movements in people with PFP. The combination of these interventions can reduce frontal knee and hip movements, and can increase sagittal knee movements. J Orthop Sports Phys Ther 2023;53(12):1-13. Epub 14 September 2023. doi:10.2519/jospt.2023.11956.

Occult hepatitis B - the result of the host immune response interaction with different genomic expressions of the virus.

With over 40 years of history, occult hepatitis B infection (OBI) continues to remain an important and challenging public health problem. Defined as the presence of replication-competent hepatitis B virus (HBV) DNA (i.e., episomal HBV covalently closed circular DNA) in the liver and/or HBV DNA in the blood of people who test negative for hepatitis B surface antigen (HBsAg) in currently available assays, OBI is currently diagnosed using polymerase chain reaction (PCR) and real-time PCR assays. However, all efforts should be made to exclude a false negative HBsAg in order to completely follow the definition of OBI. In recent years, significant advances have been made in understanding the HBV lifecycle and the molecular mechanisms that lead to the persistence of the virus in the occult form. These factors are mainly related to the host immune system and, to a smaller proportion, to the virus. Both innate and adaptive immune responses are important in HBV infection management, and epigenetic changes driven by host mechanisms (acetylation, methylation, and microRNA implication) are added to such actions. Although greater genetic variability in the S gene of HBV isolated from OBIs was found compared with overt infection, the mechanisms of OBI are not mainly viral mutations.

Valorization of tannery solid wastes for sustainable enzyme induced carbonate precipitation process.

Biocementation via enzyme induced carbonate precipitation (EICP) is an emerging ground improvement technique that utilizes urease for calcium carbonate precipitation. Usage of expensive laboratory grade chemicals in EICP hinders its implementation at field level applications. In this study, the feasibility of utilizing solid wastes generated from leather industry was investigated for EICP process. Initially, the proteinaceous fleshing waste was used as nitrogen source for production of an extracellular urease from Arthrobacter creatinolyticus MTCC 5604 followed by its subsequent use in EICP with suspended solids of tannery lime liquor, as alternative calcium source. The calcium ion solution was prepared by treating suspended solids of lime liquor with 1 N HCl. The EICP was optimum with 1000 U of urease, 1.0 M urea and 1.0 M CaCl2.2H2O for test tube experiments. Sand solidification experiments under optimal conditions with five times addition of cementation solution yielded a maximum unconfined compressive strength (UCS) of 810 kPa with laboratory grade CaCl2.2H2O and 780 kPa with calcium from lime liquor. The crystalline phases and morphology of the CaCO3 precipitate were analyzed by XRD, FTIR and SEM-EDX. The results showed the formation of more stable calcite in EICP with calcium obtained from lime liquor, while calcite and vaterite polymorphs were obtained with CaCl2.2H2O. Utilization of fleshing waste and lime liquor in EICP could reduce the pollution load and sludge formation that are generated during the pre-tanning operations of leather manufacturing. The results indicated the viability of process to achieve cost effective and sustainable biocementation for large scale applications.

Histopathologically Confirmed Pulmonary Mucormycosis as a Complication of COVID-19: a Case Report from Romania and Insight into Pathology.

COVID-19 has proven to be an independent risk factor for secondary infectious complications. Amongst them, mucormycosis has recently been noticed more frequently than in the past. Caused by molds belonging to the Mucorales order, this is a rare, but potentially fatal infection unless adequately treated. Ear, nose and throat involvement is prevalent with often expansion to the orbit, sinuses or brain. Pulmonary, cutaneous and gastrointestinal infections are also recognized. Classical risk factors for progression to angioinvasive disease include poorly controlled diabetes mellitus, defects in phagocytic function (prolonged neutropenia, glucocorticoid treatment), immunosuppressive therapy associated with transplantation, malignancy, elevated levels of free iron as well as iron chelators (deferoxamine). In addition, immune dysregulation rendered by COVID-19 itself may contribute or solely lead to invasive mold disease. The largest experience comes from India, which has dealt with a challenging epidemic of COVID-19-associated mucormycosis (CAM). To our knowledge, no previous studies have reported CAM in Romania. We therefore present a case of severe COVID-19 pneumonia initially complicated by bacterial superinfection and secondary sepsis at admission in an unvaccinated 61-year-old male who presented in our clinic with respiratory failure and digestive symptoms. Although improvement occurred rapidly following antiviral, empiric large spectrum Intraantibiotics and pathogenic medication, unfavorable clinical course ensued later on. Biological and imaging investigations were consistent with pulmonary superinfection in the form of multiple different-sized upper right field opacities, which eventually evolved to form cavities. Differential diagnosis was thoroughly performed. Since unable to sterilize the lung by means of medication alone, the patient underwent major thoracic surgery with removal of the entire right lung. Microscopic study of the damaged tissue was able to determine the presence of broad, aseptate hyphae which morphologically belong to Mucorales. A diagnosis of pulmonary mucormycosis was established and proper antifungal treatment was initiated, with full recovery of the patient.

Acute severe hepatitis outbreak in children: A perfect storm. What do we know, and what questions remain?

During the first half of 2022, the World Health Organization reported an outbreak of acute severe hepatitis of unknown aetiology (AS-Hep-UA) in children, following initial alerts from the United Kingdom (UK) where a cluster of cases was first observed in previously well children aged <6 years. Sporadic cases were then reported across Europe and worldwide, although in most countries incidence did not increase above the expected baseline. There were no consistent epidemiological links between cases, and microbiological investigations ruled out known infectious causes of hepatitis. In this review, we explore the evidence for the role of viral infection, superimposed on a specific host genetic background, as a trigger for liver pathology. This hypothesis is based on a high prevalence of Human Adenovirus (HAdV) 41F in affected children, together with metagenomic evidence of adeno-associated virus (Adeno-associated viruses)-2, which is a putative trigger for an immune-mediated liver injury. Roles for superantigen-mediated pathology have also been explored, with a focus on the potential contribution of SARS-CoV-2 infection. Affected children also had a high frequency of the MHC allele HLA-DRB1*04:01, supporting an immunological predisposition, and may have been vulnerable to viral coinfections due to disruption in normal patterns of exposure and immunity as a result of population lockdowns during the COVID-19 pandemic. We discuss areas of ongoing uncertainty, and highlight the need for ongoing scrutiny to inform clinical and public health interventions for this outbreak and for others that may evolve in future.

Assessing Seasonality Variation with Harmonic Regression: Accommodations for Sharp Peaks.

The use of the harmonic regression model is well accepted in the epidemiological and biostatistical communities as a standard procedure to examine seasonal patterns in disease occurrence. While these models may provide good fit to periodic patterns with relatively symmetric rises and falls, for some diseases the incidence fluctuates in a more complex manner. We propose a two-step harmonic regression approach to improve the model fit for data exhibiting sharp seasonal peaks. To capture such specific behavior, we first build a basic model and estimate the seasonal peak. At the second step, we apply an extended model using sine and cosine transform functions. These newly proposed functions mimic a quadratic term in the harmonic regression models and thus allow us to better fit the seasonal spikes. We illustrate the proposed method using actual and simulated data and recommend the new approach to assess seasonality in a broad spectrum of diseases manifesting sharp seasonal peaks.

Non-enzymatic reduction of Cr (VI) and it's effective biosorption using heat-inactivated biomass: A fermentation waste material.

The effectiveness of heat-inactivated fungal biomass a fermentation waste of newly isolated laccase enzyme producer Leiotrametes flavida was studied for Cr (VI) removal in water and applied for Cr (VI) removal from tannery effluent. Adsorption parameters pH, biomass concentration and contact time were optimized using Box-Behnken design of response surface methodology. The adsorption process fits the Langmuir isotherm. Thermodynamic and kinetic studies showed that the process is spontaneous at ambient temperature and followed the second-order kinetics model, respectively. The values of the kinetic model indicated that the adsorption process is a combination of physisorption and chemisorption. Chromium adsorption onto the biomass was confirmed by SEM-EDAX, FTIR, XPS and XRD analysis. XPS analysis confirmed the reduction of Cr (VI) to Cr (III). The amount of chromium adsorbed was 72.38 % and 68.33 % for water and effluent, respectively. Chromium adsorbed onto biomass was desorbed at pH 9 with 1 M NaOH. Total chromium desorbed was 61.40 and 59.38 percent from water and effluent, respectively. The amount of Cr (III) in the desorbed sample was 71 and 68 percent, respectively. The heat-inactivated biomass of Leiotrametes flavida is a suitable material for efficient Cr (VI) removal and detoxification.