A welfare analysis of Medicaid and recidivism.

We present conservative estimates for the marginal value of public funds (MVPF) associated with providing Medicaid to inmates exiting prison. The MVPF measures the ratio between a policy's social benefits and its governmental costs. Our MVPF estimates suggest that every additional $1 the government spends on providing inmates exiting prison with Medicaid coverage can result in social benefits ranging between $3.45 and $10.62. A large proportion of the benefits we consider stems from the reduced future criminal involvement among former inmates who receive Medicaid. Employing a difference-in-differences approach, we find that Medicaid expansions reduce the average number of times a released inmate is reimprisoned within 1 year by approximately 11.5%. By combining this estimate with key values reported elsewhere (e.g., victimization costs, data on victimization and incarceration), we quantify specific benefits arising from the policy. These encompass diminished criminal harm due to lower reoffense rates, direct benefits to former inmates through Medicaid coverage, increased employment opportunities, and reduced loss of liberty resulting from fewer future reimprisonments. Net-costs consist of the cost of providing Medicaid net of changes in the governmental cost of imprisonment, changes in the tax revenue due to increased employment, and changes in spending on other public assistance programs. We interpret our estimates as conservative since we deliberately err on the side of under-estimating benefits and over-estimating costs when data on specific items are imprecise or incomplete. Our findings align closely with others in the sparse literature investigating the crime-related welfare impacts of Medicaid access, underscoring the substantial indirect benefits public health insurance programs can offer through crime reduction, in addition to their direct health-related advantages.

A genome-wide RNAi screen identifies potential drug targets in a C. elegans model of α1-antitrypsin deficiency.

α1-Antitrypsin deficiency (ATD) is a common genetic disorder that can lead to end-stage liver and lung disease. Although liver transplantation remains the only therapy currently available, manipulation of the proteostasis network (PN) by small molecule therapeutics offers great promise. To accelerate the drug-discovery process for this disease, we first developed a semi-automated high-throughput/content-genome-wide RNAi screen to identify PN modifiers affecting the accumulation of the α1-antitrypsin Z mutant (ATZ) in a Caenorhabditis elegans model of ATD. We identified 104 PN modifiers, and these genes were used in a computational strategy to identify human ortholog-ligand pairs. Based on rigorous selection criteria, we identified four FDA-approved drugs directed against four different PN targets that decreased the accumulation of ATZ in C. elegans. We also tested one of the compounds in a mammalian cell line with similar results. This methodology also proved useful in confirming drug targets in vivo, and predicting the success of combination therapy. We propose that small animal models of genetic disorders combined with genome-wide RNAi screening and computational methods can be used to rapidly, economically and strategically prime the preclinical discovery pipeline for rare and neglected diseases with limited therapeutic options.

Effects of Ticagrelor on Ionic Currents and Contractility in Rat Ventricular Myocytes.

PURPOSE: Antiplatelet therapy has been widely used for management of patients with ischaemic heart diseases or thrombotic events. Experimental studies have shown that ticlopidine and clopidogrel decreased L-type Ca(2+) currents (ICaL), altered action potential (AP) duration and thence exerted negative inotropic effects. In this study we tested if ticagrelor, a non-thienopyridine agent, has any influence on contractile and electrical properties of isolated ventricular myocytes. METHODS: Cardiomyocytes were isolated from male rat hearts with an enzymatic dissociation procedure and left ventricular myocytes were used for experiments. The effects of ticagrelor (1 µM) on sarcomere shortening, ionic currents and action potentials were measured at 36 ± 1 °C. RESULTS: Ticagrelor significantly reduced ICaL density (~18%, p < 0.01) of ventricular myocytes and this effect was reversible. In consistence, it also decreased sarcomere shortening of electrically stimulated cardiomyocytes (13%, p < 0.05), while it did not change relaxation rates. Repolarizing K(+) currents and AP duration were unaffected by 1 µM ticagrelor application. CONCLUSIONS: Ticagrelor exerts a significant influence on contractile properties and membrane currents of ventricular myocytes similarly to thienopyridine agents. The impact of ticagrelor on cardiac excitation-contraction coupling elements is important, since it is widely used for the treatment of patients with heart diseases.

Remote Targets for Right Coronary Artery Bypass: Distal Trunk or Posterior Descending Artery Grafting.

BACKGROUND: Choosing a good anastomotic site is crucial during surgical revascularization of the right coronary artery (RCA) system. In many instances of distal and/or sequential main trunk disease, either the right posterior descending coronary artery (RPDA) or distal part of the right main coronary artery (DRCA) is preferred as the target vessel. In this article, the saphenous vein graft (SVG) patency is compared between these two main targets in the long term. MATERIALS AND METHODS: Postoperative control coronary angiograms were obtained and assessed from 452 patients undergoing conventional on-pump coronary artery bypass grafting with either a DRCA (n = 305) or a RPDA graft (n = 147) after an average postoperative period of 5.8 ± 4.3 years (range: 2 months-20 years; a total of 2,627 patient-years). RESULTS: The overall graft patency was 60%. The 15-year patency rate was better for the DRCA grafts than that for the RPDA grafts (32 ± 5% vs. 19 ± 6%, respectively; p = 0.001), irrespective of target vessel caliber. Other factors adversely influencing the long-term graft patency were poor target vessel quality (p = 0.002) and hypercholesterolemia (p = 0.01). On the other hand, target vessel diameter, diabetes mellitus, hypertension, chronic renal insufficiency, obesity, peripheral arterial disease, or SVG quality were not associated with poor long-term graft patency in these patients having distal-type RCA disease. CONCLUSIONS: In the presence of distal and/or sequential right coronary disease, DRCA may be the target vessel of choice for bypass grafting, rather than the RPDA, mainly for better long-term SVG patency rates in this location.

[Adult patients treated for focal epilepsy with antiepileptic drugs (AEDs) in combination in France: description according to the 2009 ILAE definition of AED resistance (ESPERA study)]. / Patients adultes traités par une association d'antiépileptiques pour une épilepsie focale en France: description et mode de prise en charge selon les nouveaux critères de définition de la pharmacorésistance (étude ESPERA).

AIMS: To describe the adult population treated with antiepileptic drugs (AEDs) in combination for focal epilepsy according to the definition of AED resistance proposed by the International League Against Epilepsy (ILAE) in 2009 and to evaluate its implementation in current practice. METHODS: ESPERA was a multicenter, observational, cross-sectional study with a clinical data collection covering the past 12 months conducted by neurologists. Classifications according to AED responsiveness established by investigators for each enrolled patient were revised by two experts. RESULTS: Seventy-one neurologists enrolled 405 patients. Their mean age was 42.7 years (sex-ratioM/F 0.98). According to the investigators, 60% of epilepsies were drug-resistant, 37% drug-responsive and 3% had an undefined drug-responsiveness. After revision of experts, 71% of epilepsies were classified as drug resistant, 22% as responsive and 7% as undefined. Among the participating neurologists, 76% have made at least one error in classifying their patients according to the 2009 ILAE definition of AED resistance. Because of epilepsy, 24% of patients (age≤65) were inactive and 42% could not drive (respectively 29 and 49% of patients with AED resistant epilepsy). Half of patients had at least one other chronic condition. Number of prescribed drugs in combination and health care resource utilisation were significantly higher in patients with drug-resistant epilepsies than in patients with drug responsive epilepsies. CONCLUSION: ESPERA study shows that the use of new definition of drug-resistance in everyday practice seems difficult without any additional training and that the social and professional disability is frequent in adults with focal epilepsies treated with polytherapy.

An improved method compatible with metagenomic analyses to extract genomic DNA from soils in Tuber melanosporum orchards.

AIMS: The development of high-throughput methods such as pyrosequencing and microarrays has greatly improved our understanding of the microbial diversity in complex environments such as soils. Nevertheless, albeit advancements in such techniques, the first major step is to obtain high quantity and good quality genomic DNA (gDNA). The work presented here aims to present an inherent problem with 260 : 230 nm ratio of extracted gDNA from calcareous soils of Tuber melanosporum orchards and a protocol to overcome this problem. METHODS AND RESULTS: Using two commercial gDNA extraction kits on spatially distant truffle orchards, we demonstrated that the 260 : 230 nm ratio was very low, consequentially yielding gDNA incompatible with microarray analyses. In order to solve this problem, optimization steps were tested including several wash steps performed before and/or after lysis. These washes significantly improved the gDNA quality (ratio 260 : 230 nm >1·7) without modification of the structure of the bacterial communities as stated by temporal temperature gradient gel electrophoresis analysis. A final re-extraction with phenol/chloroform was required for one of the soil samples. CONCLUSIONS: A combination of wash steps included into the extraction protocol followed by phenol: chloroform re-extraction is recommended to obtain high-quality gDNA from calcareous soils of T. melanosporum orchards. SIGNIFICANCE AND IMPACT OF THE STUDY: The method recommended here significantly improves gDNA quality obtained from T. melanosporum orchards to make it acceptable for highly sensitive methods such as microarray.

Contributions of Ccr4 and Gcn2 to the Translational Response of C. neoformans to Host-Relevant Stressors and Integrated Stress Response Induction.

In response to the host environment, the human pathogen Cryptococcus neoformans must rapidly reprogram its translatome from one which promotes growth to one which is responsive to host stress. In this study, we investigate the two events which comprise translatome reprogramming: the removal of abundant, pro-growth mRNAs from the translating pool, and the regulated entry of stress-responsive mRNAs into the translating pool. Removal of pro-growth mRNAs from the translating pool is controlled primarily by two regulatory mechanisms, repression of translation initiation via Gcn2, and decay mediated by Ccr4. We determined that translatome reprogramming in response to oxidative stress requires both Gcn2 and Ccr4, whereas the response to temperature requires only Ccr4. Additionally, we assessed ribosome collision in response to host-relevant stress and found that collided ribosomes accumulated during temperature stress but not during oxidative stress. The phosphorylation of eIF2α that occurred as a result of translational stress led us to investigate the induction of the integrated stress response (ISR). We found that eIF2α phosphorylation varied in response to the type and magnitude of stress, yet all tested conditions induced translation of the ISR transcription factor Gcn4. However, Gcn4 translation did not necessarily result in canonical Gcn4-dependent transcription. Finally, we define the ISR regulon in response to oxidative stress. In conclusion, this study begins to reveal the translational regulation in response to host-relevant stressors in an environmental fungus which is capable of adapting to the environment inside the human host. IMPORTANCE Cryptococcus neoformans is a human pathogen capable of causing devastating infections. It must rapidly adapt to changing environments as it leaves its niche in the soil and enters the human lung. Previous work has demonstrated a need to reprogram gene expression at the level of translation to promote stress adaptation. In this work, we investigate the contributions and interplay of the major mechanisms that regulate entry of new mRNAs into the pool (translation initiation) and the clearance of unneeded mRNAs from the pool (mRNA decay). One result of this reprogramming is the induction of the integrated stress response (ISR) regulon. Surprisingly, all stresses tested led to the production of the ISR transcription factor Gcn4, but not necessarily to transcription of ISR target genes. Furthermore, stresses result in differential levels of ribosome collisions, but these are not necessarily predictive of initiation repression as has been suggested in the model yeast.

Beech roots are simultaneously colonized by multiple genets of the ectomycorrhizal fungus Laccaria amethystina clustered in two genetic groups.

In this study, we characterize and compare the genetic structure of aboveground and belowground populations of the ectomycorrhizal fungus Laccaria amethystina in an unmanaged mixed beech forest. Fruiting bodies and mycorrhizas of L. amethystina were mapped and collected in four plots in the Swietokrzyskie Mountains (Poland). A total of 563 fruiting bodies and 394 mycorrhizas were successfully genotyped using the rDNA IGS1 (intergenic spacer) and seven simple sequence repeat markers. We identified two different genetic clusters of L. amethystina in all of the plots, suggesting that a process of sympatric isolation may be occurring at a local scale. The proportion of individuals belonging to each cluster was similar among plots aboveground while it significantly differed belowground. Predominance of a given cluster could be explained by distinct host preferences or by priority effects and competition among genets. Both aboveground and belowground populations consisted of many intermingling small genets. Consequently, host trees were simultaneously colonized by many L. amethystina genets that may show different ecophysiological abilities. Our data showed that several genets may last for at least 1 year belowground and sustain into the next season. Ectomycorrhizal species reproducing by means of spores can form highly diverse and persistent belowground genets that may provide the host tree with higher resilience in a changing environment and enhance ecosystem performance.

Long Non-Coding RNAs in Cryptococcus neoformans: Insights Into Fungal Pathogenesis.

Long non-coding RNAs (lncRNAs) are highly expressed and can modulate multiple cellular processes including transcription, splicing, translation, and many diverse signaling events. LncRNAs can act as sponges for miRNAs, RNA and DNA binding proteins, functioning as competitive endogenous RNAs. The contribution of lncRNAs to microbial pathogenesis is largely neglected in eukaryotic pathogens despite the abundance of RNA sequencing datasets encompassing conditions of stress, gene deletions and conditions that mimic the host environment. The human fungal pathogen Cryptococcus neoformans encodes 6975 (84%) protein-coding and 1359 (16%) non-protein-coding RNAs, of which 1182 (14.2%) are lncRNAs defined by a threshold of greater than 200 nucleotides in length. Here, we discuss the current state of knowledge in C. neoformans lncRNA biology. Utilizing existing RNA seq datasets, we examine trends in lncRNA expression and discuss potential implications for pathogenesis.

Rare coexistence of Tay-Sachs disease, coarctation of the aorta and grade V vesicoureteral reflux. / Coexistencia infrecuente de la enfermedad de Tay-Sachs, coartación aórtica y reflujo vesicoureteral de grado V.

Tay-Sachs disease is a neurodegenerative inherited metabolic disease. There are four forms classified by the time of first clinical symptoms: infantile, late infantile, juvenile and adult. Infantile , Ebru Candab, Ertürk Leventc , The infantile form has the poorest clinical prognosis. First symptoms of this form, such as muscle weakness and hypotonia, occur around form has the poorest prognosis. Lately, different abnormalities which accompany metabolic disorders and affect the prognosis have been described. We present an infant with Tay-Sachs disease accompanied by coarctation of the aorta and bilateral grade V vesicoureteral reflux (VUR). The patient was followed up in the outpatient clinic of Pediatric Cardiology. The abdominal ultrasonography showed pelvicalyceal ectasia; bilateral grade V VUR in voiding cystourethrography was found. This coexistence has not been previously reported. This case emphasizes that abnormalities in the neurological examination of cardiac postsurgical patients should not be underestimated because the opportunity to diagnose inborn errors of metabolism could be missed.

La enfermedad de Tay-Sachs es una enfermedad metabólica hereditaria neurodegenerativa. Existen cuatro tipos según el inicio de los síntomas clínicos: infantil, infantil de inicio tardío, juvenil y adulto. El tipo infantil tiene el peor pronóstico. Recientemente, se describieron diferentes anomalías que acompañan a los trastornos metabólicos e influyen en el pronóstico. Presentamos el caso de un lactante con enfermedad de Tay-Sachs junto con coartación aórtica y reflujo vesicoureteral bilateral (RVU) de grado V. Se realizó el seguimiento del paciente en el consultorio externo de Cardiología Pediátrica. En la ecografía abdominal, se observó ectasia pielocalicial, y se detectó reflujo vesicoureteral bilateral de grado V en la cistouretrografía miccional. No se ha informado previamente la coexistencia de estas anomalías. Este caso pone de manifiesto que no se deben subestimar las anomalías del examen neurológico en los pacientes con una cirugía cardíaca reciente, porque podría perderse la oportunidad de diagnosticar enzimopatías congénitas.

Distribution and localization of microsatellites in the Perigord black truffle genome and identification of new molecular markers.

The level of genetic diversity and genetic structure in the Perigord black truffle (Tuber melanosporum Vittad.) has been debated for several years, mainly due to the lack of appropriate genetic markers. Microsatellites or simple sequence repeats (SSRs) are important for the genome organisation, phenotypic diversity and are one of the most popular molecular markers. In this study, we surveyed the T. melanosporum genome (1) to characterise its SSR pattern; (2) to compare it with SSR patterns found in 48 other fungal and three oomycetes genomes and (3) to identify new polymorphic SSR markers for population genetics. The T. melanosporum genome is rich in SSRs with 22,425 SSRs with mono-nucleotides being the most frequent motifs. SSRs were found in all genomic regions although they are more frequent in non-coding regions (introns and intergenic regions). Sixty out of 135 PCR-amplified mono-, di-, tri-, tetra, penta, and hexa-nucleotides were polymorphic (44%) within black truffle populations and 27 were randomly selected and analysed on 139 T. melanosporum isolates from France, Italy and Spain. The number of alleles varied from 2 to 18 and the expected heterozygosity from 0.124 to 0.815. One hundred and thirty-two different multilocus genotypes out of the 139 T. melanosporum isolates were identified and the genotypic diversity was high (0.999). Polymorphic SSRs were found in UTR regulatory regions of fruiting bodies and ectomycorrhiza regulated genes, suggesting that they may play a role in phenotypic variation. In conclusion, SSRs developed in this study were highly polymorphic and our results showed that T. melanosporum is a species with an important genetic diversity, which is in agreement with its recently uncovered heterothallic mating system.

Cryptococcus neoformans Coinfection Dampens the TNF-α Response in HIV-1-Infected Human THP-1 Macrophages.

Cryptococcus neoformans is a devastating opportunistic fungal pathogen. It mostly impacts people in an immunocompromised state, such as people living with HIV/AIDS and following organ transplantation. Macrophages, in addition to being a major cellular reservoir of HIV-1, represent a unique niche in which both C. neoformans and HIV-1 can coinhabit in the course of natural infection. Here, we report the observation that HIV-1 infection of THP-1 macrophages increases the rate at which they phagocytose C. neoformans cells. We investigated the tumor necrosis factor alpha (TNF-α) signaling and nuclear factor kappa B (NF-κB) activation in human monocyte-derived macrophages infected with HIV-1 alone, as well as those coinfected with HIV-1 and C. neoformans Our findings showed that while HIV-1 infection alone upregulates TNF-α production and activates NF-κB signaling, C. neoformans coinfection drastically and rapidly dampens this proinflammatory response. These data suggest an antagonism between two important human pathogens during coinfection of macrophages.IMPORTANCE Fungal infections are one of the leading causes of death for people who live with HIV/AIDS. Even though these pathogens are independently well studied, it is still enigmatic how coinfection with HIV-1 and C. neoformans alters gene expression and cellular processes, especially in clinically relevant cell types. Understanding the interplay between these two pathogens is especially critical because C. neoformans mortality largely depends on the host's immunocompromised state during viral infection. Studying this coinfection is challenging since HIV-1 only infects human cells, and the modified murine HIV-1 virus does not reproduce the clinical landmarks of HIV-1 infection or AIDS in mice. Our observations shed light on how these two pathogens trigger opposing trends in TNF-α and NF-κB signaling in human monocyte-derived macrophages.

A Conserved Gcn2-Gcn4 Axis Links Methionine Utilization and the Oxidative Stress Response in Cryptococcus neoformans.

The fungal pathogen Cryptococcus neoformans relies on post-transcriptional mechanisms of gene regulation to adapt to stressors it encounters in the human host, such as oxidative stress and nutrient limitation. The kinase Gcn2 regulates translation in response to stress by phosphorylating the initiation factor eIF2, and it is a crucial factor in withstanding oxidative stress in C. neoformans, and amino acid limitation in many fungal species. However, little is known about the role of Gcn2 in nitrogen limitation in C. neoformans. In this study, we demonstrate that Gcn2 is required for C. neoformans to utilize methionine as a source of nitrogen, and that the presence of methionine as a sole nitrogen source induces eIF2 phosphorylation. The stress imposed by methionine leads to an oxidative stress response at both the levels of transcription and translation, as seen through polysome profiling as well as increased abundance of select oxidative stress response transcripts. The transcription factor Gcn4 is also required for methionine utilization and oxidative stress resistance, and RT-qPCR data suggests that it regulates expression of certain transcripts in response to oxidative stress. The results of this study suggest a connection between nitrogen metabolism and oxidative stress in C. neoformans that is mediated by Gcn4, possibly indicating the presence of a compound stress response in this clinically important fungal pathogen.

Puf4 Mediates Post-transcriptional Regulation of Cell Wall Biosynthesis and Caspofungin Resistance in Cryptococcus neoformans.

The human fungal pathogen Cryptococcus neoformans is intrinsically resistant to the echinocandin antifungal drug caspofungin, which targets the ß-1,3-glucan synthase encoded by FKS1 Echinocandins have been on the market for 20 years, yet they are the newest class of antifungal drugs. Analysis of a C. neoformanspuf4Δ mutant, lacking the pumilio/FBF RNA binding protein family member Puf4, revealed exacerbated caspofungin resistance. In contrast, overexpression of PUF4 resulted in caspofungin sensitivity. The FKS1 mRNA contains three Puf4-binding elements (PBEs) in its 5' untranslated region. Puf4 binds with specificity to this region of FKS1 The FKS1 mRNA was destabilized in the puf4Δ mutant, and the abundance of the FKS1 mRNA was reduced compared to wild type, suggesting that Puf4 is a positive regulator of FKS1 mRNA stability. In addition to FKS1, the abundance of additional cell wall biosynthesis genes, including chitin synthases (CHS3, CHS4, and CHS6) and deacetylases (CDA1, CDA2, and CDA3) as well as a ß-1,6-glucan synthase gene (SKN1), was regulated by Puf4. The use of fluorescent dyes to quantify cell wall components revealed that the puf4Δ mutant had increased chitin content, suggesting a cell wall composition that is less reliant on ß-1,3-glucan. Overall, our findings suggest a mechanism by which caspofungin resistance, and more broadly, cell wall biogenesis, is regulated post-transcriptionally by Puf4.IMPORTANCECryptococcus neoformans is an environmental fungus that causes pulmonary and central nervous system infections. It is also responsible for 15% of AIDS-related deaths. A significant contributor to the high morbidity and mortality statistics is the lack of safe and effective antifungal therapies, especially in resource-poor settings. Yet, antifungal drug development has stalled in the pharmaceutical industry. Therefore, it is essential to understand the mechanism by which C. neoformans is resistant to caspofungin to design adjunctive therapies to potentiate the drug's activity toward this important pathogen.

Quantitative Proteomics Identifies Secreted Diagnostic Biomarkers as well as Tumor-Dependent Prognostic Targets for Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the third most common and most malignant urological cancer, with a 5-year survival rate of 10% for patients with advanced tumors. Here, we identified 10,160 unique proteins by in-depth quantitative proteomics, of which 955 proteins were significantly regulated between tumor and normal adjacent tissues. We verified four putatively secreted biomarker candidates, namely, PLOD2, FERMT3, SPARC, and SIRPα, as highly expressed proteins that are not affected by intratumor and intertumor heterogeneity. Moreover, SPARC displayed a significant increase in urine samples of patients with ccRCC, making it a promising marker for the detection of the disease in body fluids. Furthermore, based on molecular expression profiles, we propose a biomarker panel for the robust classification of ccRCC tumors into two main clusters, which significantly differed in patient outcome with an almost three times higher risk of death for cluster 1 tumors compared with cluster 2 tumors. Moreover, among the most significant clustering proteins, 13 were targets of repurposed inhibitory FDA-approved drugs. Our rigorous proteomics approach identified promising diagnostic and tumor-discriminative biomarker candidates which can serve as therapeutic targets for the treatment of ccRCC. IMPLICATIONS: Our in-depth quantitative proteomics analysis of ccRCC tissues identifies the putatively secreted protein SPARC as a promising urine biomarker and reveals two molecular tumor phenotypes.

Do comorbidities influence objective and subjective recovery rates of nasal polyposis?

OBJECTIVES: To investigate the clinical and laboratory outcomes both objectively and subjectively in nasal polyposis patients with or without comorbidity (CoM; asthma and allergy). PATIENTS AND METHODS: Thirty-three nasal polyposis patients (13 women and 20 men) were included into the study. Their mean age was 39.23 +/- 9.13 years. CoM(+) and CoM(-) nasal polyposis patients were compared with each other. Evaluations contained endoscopic nasal examination, acoustic rhinometry, rhinomanometry, visual analog scale score of nasal blockage, olfactory function score, respiratory function test, skin prick tests, and paranasal sinus computed tomography. RESULTS: Recovery was statistically significant in all observed evaluations for endoscopic and radiologic staging, nasal obstruction, and sense of smell compared with the first evaluation in all patients regardless of the subgroups. Although objective measurements of respiratory functions did not show any change, clinical improvement was detected in CoM(+) patients with a decrease of need to their antiasthmatic medical treatment. CONCLUSIONS: Results of CoM(+) patients led to no statistical difference when compared with CoM(-) subgroup. When applying predefined nasal polyposis treatment protocol, the polyp patients with CoMs do not need close follow-up compared to the patients without CoMs.

Access to substance use disorder treatment during COVID-19: Implications from reduced local jail populations.

Many states have responded to the spread of COVID-19 by implementing policies which have led to a dramatic reduction in jail populations. We consider the benefits associated with providing the population of individuals who would, but for these policies, be incarcerated with substance use disorder (SUD) treatment. We discuss problems that may prevent this population from receiving SUD treatment as well as policies which may mitigate these problems.

454 Pyrosequencing analyses of forest soils reveal an unexpectedly high fungal diversity.

* Soil fungi play a major role in ecological and biogeochemical processes in forests. Little is known, however, about the structure and richness of different fungal communities and the distribution of functional ecological groups (pathogens, saprobes and symbionts). * Here, we assessed the fungal diversity in six different forest soils using tag-encoded 454 pyrosequencing of the nuclear ribosomal internal transcribed spacer-1 (ITS-1). No less than 166 350 ITS reads were obtained from all samples. In each forest soil sample (4 g), approximately 30 000 reads were recovered, corresponding to around 1000 molecular operational taxonomic units. * Most operational taxonomic units (81%) belonged to the Dikarya subkingdom (Ascomycota and Basidiomycota). Richness, abundance and taxonomic analyses identified the Agaricomycetes as the dominant fungal class. The ITS-1 sequences (73%) analysed corresponded to only 26 taxa. The most abundant operational taxonomic units showed the highest sequence similarity to Ceratobasidium sp., Cryptococcus podzolicus, Lactarius sp. and Scleroderma sp. * This study validates the effectiveness of high-throughput 454 sequencing technology for the survey of soil fungal diversity. The large proportion of unidentified sequences, however, calls for curated sequence databases. The use of pyrosequencing on soil samples will accelerate the study of the spatiotemporal dynamics of fungal communities in forest ecosystems.

Endoscopic removal technique of a huge ethmoido-orbital osteoma.

Osteomas are slow-growing benign tumors of the paranasal sinuses. They originate from the sinus wall and generally fills the sinus cavity. Many osteomas are asymptomatic and diagnosed incidentally on radiographs. The well-circumscribed, dense bony appearance on radiographs is usually diagnostic. Osteomas become symptomatic when they extend to the orbit or cranium. We report a rare case of ethmoido-orbital osteoma. Case reports and a review of the literature concerning osteoma and surgical techniques are presented. Treatment is not recommended in asymptomatic osteomas. If treatment is indicated, external or endoscopic approach can be chosen. The choice of surgical approach depends on the size of the lesion, location, and the experience of the surgeon.

Improving the repeatability of two-rate model parameter estimations by using autoencoder networks.

The adaptive changes elicited in visuomotor adaptation experiments are usually well explained at group level by two-rate models (Smith et al., 2006), but parameters fitted to individuals show considerable variance. Data cleaning can mitigate this problem, but the assumption of smoothness can be problematic due to fast adaptive changes with discontinuous derivatives. In this paper, we collected time-series data from an experimental paradigm involving repeated training and investigated the effect of various cleaning methods, including an autoencoder network (AE), on the parameter estimation. We compared changes in the fitted parameters across different methods and across training repetitions. The results suggest that AE performed best overall, without introducing an underestimation bias on bf like moving average or piecewise polynomials, and that it reduced the within-subject variance overall and especially that of the fast retention rate af by >50%.