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•UDs transplant with PTCY for myelodysplastic neoplasms may improve OS and PFS as compared with ATG.•PTCY may also decrease the incidence of grade 2 to 4 acute GVHD.

Faecal microbiota transplantation (FMT) aims to restore intestinal microbiota balance with the objective of normalising its composition and achieve therapeutic benefits. The procedure involves the administration of fresh or frozen faecal microbes from a healthy donor into the recipient’s gastrointestinal tract with the intent to restore the proper structure and functionality of the recipient’s intestinal microbial community. Evidence showing the positive effects of FMT is abundant, however, less attention has been devoted to FMT-associated adverse events, especially in relation to liver diseases. Based on literature review, studies and reports regarding FMT-associated adverse events since the beginning of FMT use, have been analysed. The review covering the period 2010-2022 was undertaken in accordance with the PRISMA guidelines.

We retrospectively compared outcomes of 404 MDS patients undergoing 1st matched sibling donor allo-HCT receiving either PTCy-based (n= 66) or other “conventional prophylaxis” (n= 338; mostly calcineurin inhibitor + methotrexate or MMF). Baseline characteristics were balanced, except for higher use of myeloablative regimens in the PTCy group (52.3% vs. 38.2%, p= 0.047). Incidences of neutrophil (Day +28: 89% vs. 97%, p= 0.011) and platelet (Day +100: 89% vs. 97%, p< 0.001) engraftment were lower for PTCy-based. Day +100 cumulative incidences of grade II–IV and III–IV aGVHD, and 5-year CI of extensive cGVHD were 32%, 18% and 18% for PTCy-based and 25% (p= 0.3), 13% (p= 0.4) and 31% (p= 0.09) for the conventional cohort. Five-year OS (51% vs. 52%, p= 0.6) and GRFS (33% vs. 25%, p= 0.6) were similar between groups. Patients receiving PTCy had a trend to a lower cumulative incidence of relapse (20% vs. 33%, p= 0.06), not confirmed on multivariable analysis (p= 0.3). Although higher NRM rates were observed in patients receiving PTCy (32% vs. 21%, p= 0.02) on univariate analysis, this was not confirmed on multivariate analysis (HR 1.46, p= 0.18), and there was no resultant effect on OS (HR 1.20, p= 0.5). Based on these data, PTCy prophylaxis appears to be an attractive option for patients with MDS undergoing MSD allo-HCT.

The light absorbing component of organic aerosols, brown carbon (BrC), directly affects climate and can play a role in the oxidative aging of organic aerosols. Recent estimates suggest that globally BrC may have a warming potential that is approximately 20% that of black carbon, and photochemistry from BrC compounds can increase or transform aqueous SOA. Photobleaching of BrC is estimated to occur with a timescale of hours to days, a range that complicates estimates of the effects of BrC on climate and aerosol chemistry. The chemical environment (e.g.pH, ionic strength, and non-BrC organic content) of aqueous aerosols can also affect the reactivity of BrC, potentially altering absorption spectra and reactions of excited states formed upon irradiation. A range of solar illumination sources have been used in studying the photochemistry of BrC compounds, making direct comparisons between results difficult. Higher energy, single wavelength studies (e.g.308 nm) show much larger quantum yields than broadband studies, indicating wavelength dependent quantum yields for a wide range of atmospherically relevant substituted aromatics. In this work we investigate the wavelength dependence of the quantum yield for loss of a prototypical BrC compound found in wildfire emissions, vanillin, using several narrow band UV-LEDs that span the 295–400 nm range. These wavelength dependent quantum yields will allow a more direct comparison between photochemical experiments with laboratory irradiation sources and actual actinic fluxes. Vanillin photochemical loss rates are concentration-dependent due to direct reaction between triplet excited state and ground state vanillin molecules. The quantum yield for photochemical loss of vanillin can be approximated by a Gaussian decay from 295 nm to ∼365 nm. This function is used to directly calculate the solar zenith angle (SZA) dependence for photochemical loss. Computational results show the presence of two π → π* transitions responsible for the observed UV-vis spectrum and that the rate of intersystem crossing has a wavelength dependence remarkably similar to that of the quantum yield for loss. A strong kinetic salt effect is observed, showing a doubling of the loss rate at high ionic strength.

Therapy-related myeloid neoplasms (t-MN), either myelodysplastic neoplasms (t-MDS) or acute myeloid leukemias (t-AML), have a poor prognosis and allogeneic haematopoietic cell transplantation (allo-HCT) represents the only curative option. In this multicenter, registry-based study, we analyzed outcomes of 378 patients undergoing first allo-HCT between 2006–2017 for t-MN arising secondary to lymphoma treatment. Median age was 58 years at allo-HCT; 222 (59%) had a diagnosis of t-MDS and 156 (41%) of t-AML, respectively. At the time of allo-HCT, 46% of t-MN cases were reported as in complete remission (CR) and 15% of lymphomas were recorded as not in remission. A reduced intensity conditioning regimen was used in 70% of cases. For the entire cohort, 5-year OS, and t-MN PFS, relapse incidence and NRM were 32%, 28%, 35% and 37%, respectively. In multivariable analysis, undergoing allo-HCT with t-MN not in CR and older age were associated with significantly worse OS, PFS and NRM. At 5 years post allo-HCT, the relapse incidence of lymphoma was low at 3%, while the rate of secondary malignancies was 8%. This analysis shows the curative potential of allo-HCT for patients with t-MN arising secondary to lymphoma treatment in approximately a third of patients.

Management of Richter transformation (RT) is particularly challenging, with survival estimates <1 year. We report on outcomes of 66 RT patients undergoing allogeneic-HCT (allo-HCT) between 2008 and 2018 registered with the EBMT. Median age at allo-HCT was 56.2 years (interquartile range (IQR), 51.3–63.1). Median time from RT to allo-HCT was 6.9 months (IQR, 4.9–11) and 28 (42.4%) were in complete remission (CR). The majority underwent reduced intensity conditioning (66.2%) using peripheral blood derived stem cells. Eighteen (27.3%) patients had a matched sibling donor, 24 (36.4%) a matched unrelated donor and the remaining were mismatched. Median follow-up was 6.6 years; 1- and 3- year overall and progression free survival (PFS) (95% CI) was 65% (54–77) and 39% (27–51) and 53% (41–65) and 29% (18–40), respectively. Patients in CR at time of allo-HCT had significantly better 3-year PFS (39% vs.21%, p= 0.032). Cumulative incidences of grade II–IV acute graft versus host disease (GVHD) at day +100 was 41% (95% CI 29–53) and chronic GVHD at 3 years was 53% (95% CI 41–65). High rates of non-relapse mortality (NRM) were observed; 38% (95% CI, 26–50) at 3 years. Although potentially curative, approaches to reduce considerable NRM and chronic GVHD rates are required.

We aimed to compare outcomes following treosulfan (TREO) or busulfan (BU) conditioning in a large cohort of myelofibrosis (MF) patients from the EBMT registry. A total of 530 patients were included; 73 received TREO and 457 BU (BU ≤ 6.4 mg/kg in 134, considered RIC, BU > 6.4 mg/kg in 323 considered higher dose (HD)). Groups were compared using adjusted Cox models. Cumulative incidences of engraftment and acute GVHD were similar across the 3 groups. The TREO group had significantly better OS than BU-HD (HR:0.61, 95% CI: 0.39–0.93) and a trend towards better OS over BU-RIC (HR: 0.66, 95% CI: 0.41–1.05). Moreover, the TREO cohort had a significantly better Progression-Free-Survival (PFS) than both the BU-HD (HR: 0.57, 95% CI: 0.38–0.84) and BU-RIC (HR: 0.60, 95% CI: 0.39–0.91) cohorts, which had similar PFS estimates. Non-relapse mortality (NRM) was reduced in the TREO and BU-RIC cohorts (HR: 0.44, 95% CI: 0.24–0.80 TREO vs BU-HD; HR: 0.54, 95% CI: 0.28–1.04 TREO vs BU-RIC). Of note, relapse risk did not significantly differ across the three groups. In summary, within the limits of a registry-based study, TREO conditioning may improve PFS in MF HSCT and have lower NRM than BU-HD with a similar relapse risk to BU-RIC. Prospective studies are needed to confirm these findings.

Bortezomib (Vel)- Melphalan 200 mg/m2 (Mel200) (Vel-Mel) has been utilised to intensify conditioning in autologous hematopoietic stem cell transplantation (AHCT) for multiple myeloma (MM). This EBMT registry-based study compared Vel-Mel with Mel200 during upfront AHCT. Between 2010 and 2017, MM patients who received Vel-Mel (n = 292) conditioning were compared with 4,096 Mel200 patients in the same 58 centres. Pre-AHCT, compared to Mel200 patients, Vel-Mel patients had similar International Staging System (ISS) scores and cytogenetic risk profiles; a similar proportion had received bortezomib-based induction (85% and 87.3%, respectively) though they were younger with a better performance status. Vel-Mel patients were more likely to achieve CR post-induction (40.6% vs 20.3%, p < 0.001) and by day 100 of AHCT (CR/VGPR: 70.2 % vs. 57.2%, p < 0.001). There was no difference in 3-year PFS (49% vs 46%, p = 0.06) or early post-AHCT mortality. In multivariable analysis, Vel-Mel associated with inferior PFS (HR: 1.69 (1.27–2.25, p < 0.001) and OS (HR:1.46 (1.14–1.86,p = 0.002), similar to negative effects on PFS of advanced ISS (HR:1.56 (1.33–1.83, p < 0.001), high-risk cytogenetics (HR:1.43(1.18–1.74, p < 0.001) and poor post-induction response(<=PR)(HR: 1.43(1.25–1.62, p < 0.001) Overall, despite superior pre- and post-AHCT responses, there was no improvement in PFS or OS following Vel-Mel. This data supports the findings of the smaller prospective IFM study.

While varying greatly in size, European clausiliids have a remarkably consistent and characteristic shell form that distinguishes them from all other land snails in the region. They are found in a wide range of habitats and are geographically widespread, occurring in boreal through to mediterranean climates. There are, however, regional differences in species richness and range sizes, and striking differences in the number of species that may be found syntopically, even in habitats that appear similar. Regions of high diversity do not always support many species co-occurring at site level. We explore these differences, using information on habitat and microhabitat differences between species to assess the extent to which co-occurrence might be limited by competition or environmental constraints. Neither provide a satisfactory explanation for all patterns, and the effects of Quaternary climate change and limited powers of dispersal are clearly important.

Molecular phylogenetic studies have provided new insights into the relationships within the highly speciose clausiliid subfamily Phaedusinae, but they have also triggered new questions about the position of Synprosphyma A. J. Wagner 1920 within that subfamily. This study shows that Synprosphyma constitutes a c. 37.3 million-year-old lineage within Clausiliidae, which is neither closely connected with the remaining Phaedusinae nor with any other clausiliid taxon. Synprosphyma is therefore placed in a separate subfamily, Synprosphyminae. It constitutes a third eastern Eurasian lineage of Clausiliidae, next to Garnieriinae and the redefined Phaedusinae. Our phylogeographic analysis points to a larger role of eastern Eurasia in the biogeographic history of Clausiliidae than previously assumed; however, it is not yet resolved whether this was as part of a wide ancestral Eurasian range of Clausiliidae or as an area that was repeatedly colonized from western Eurasia. The distributional pattern of Phaedusinae, Synprosphyminae, and Garnieriinae in Eurasia is similar to that of relict floras, which suggests similar climatic preferences coupled with a comparable role of historical range contractions and/or passive dispersal.

The possibilities of using the atomic-layer-deposition method to modify microchannel plates in order to increase their efficiency are investigated. The object of the study is two types of nanolayers: resistive and emissive. The following compositions are chosen as the resistive layer: zinc oxide and indium-tin oxide, and aluminum oxide as the emissive layer.

The recent application of whole exome or whole genome sequencing unveiled a plethora of germline variants predisposing to myeloid disorders, particularly myelodysplastic neoplasms. The presence of such variants in patients with myelodysplastic syndromes has important clinical repercussions for haematopoietic stem-cell transplantation, from donor selection and conditioning regimen to graft-versus-host disease prophylaxis and genetic counselling for relatives. No international guidelines exist to harmonise management approaches to this particular clinical scenario. Moreover, the application of germline testing, and how this informs clinical decisions, differs according to the expertise of individual clinical practices and according to different countries, health-care systems, and legislations. Leveraging the global span of the European Society for Blood and Marrow Transplantation (EBMT) network, we took a snapshot of the current European situation on these matters by disseminating an electronic survey to EBMT centres experienced in myelodysplastic syndromes transplantation. An international group of haematologists, transplantation physicians, paediatricians, nurses, and experts in molecular biology and constitutional genetics with experience in myelodysplastic syndromes contributed to this Position Paper. The panel met during multiple online meetings to discuss the results of the EBMT survey and to establish suggested harmonised guidelines for such clinical situations, which are presented here.

The primary tool that central banks have to fight recessions is to cut interest rates so as to encourage enough borrowing and spending to return the economy to full employment. [...]

ABSTRACTDeep learning models offer great potential for advancing land monitoring using satellite data. However, they face challenges due to imbalanced real-world data distributions of land cover and crop types, hindering scalability and transferability. This letter presents a novel data augmentation method employing Generative Adversarial Neural Networks (GANs) with pixel-to-pixel transformation (pix2pix). This approach generates realistic synthetic satellite images with artificial ground truth masks, even for rare crop class distributions. It enables the creation of additional minority class samples, enhancing control over training data balance and outperforming traditional augmentation methods. Implementing this method improved the overall map accuracy (OA) and intersection over union (IoU) by 1.5% and 2.1%, while average crop type classes’ user accuracy (UA) and producer accuracies (PA), as well as IoU, were improved by 11.2%, 6.4% and 10.2%.

This work reports two novel drug–drug cocrystals of antifungal clotrimazole (CLT) with nonsteroidal anti-inflammatory drugs, including niflumic acid (NFA) and diclofenac (DIC). They were synthesized by slurry and solution crystallization methods and characterized by powder and single-crystal X-ray diffraction and differential scanning calorimetry. The cocrystals were found to have similar molecular packing, and to highlight their distinctness, the crystal lattice energies and intermolecular interaction energies were calculated by using the CLP-PIXEL software package. A series of competitive slurry experiments were carried out to qualitatively assess the thermodynamic stability of the cocrystals. The solubility, dissolution, and diffusion of the novel drug–drug cocrystals were investigated in a pH 1.2 buffer solution. There is a correlation between cocrystal stability and dissolution/diffusion behavior.

In this work, the important scientific and technical problem of creating multifunctional composite materials for shipbuilding and ocean engineering was solved. The work aimed to study the thermal deformation processes of sintering glass microspheres to obtain lightweight glass composites with a cellular structure that provides positive buoyancy and sound insulation properties. For this purpose, glass microspheres of Na2O‒SiO2and Na2O‒B2O3‒SiO2composition with a dispersion of 10 to 60 μm were used as raw materials. They were sintered to form a closed, porous structure. The theoretical substantiation of technological parameters is based on the concepts of solid state and glassy state chemistry and physicochemical concepts of glass softening processes. The process of hot-pressing glass microspheres without plasticisers and additives was investigated. The author’s own laboratory equipment was used for the experiments. The sintering intensity was determined from the results of shrinkage processes; the kinetic shrinkage curves were constructed in semilogarithmic coordinates. The glass composite samples were examined by optical and electron microscopy. As a criterion, the storage of spherical microspheres under the influence of simultaneous heating to 700 °C with the application of pressure in the range of 0,5 to 1,5 MPa was chosen. It was established that the formation of a predominantly closed-porous structure of glass composites with a density of 350...600 kg/m3occurs by the mechanisms of viscous glass phase flow through liquefaction processes in the walls of microspheres. At the same time, shrinkage processes in the linear direction reach up to 50%.

The role of high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) in the treatment of myeloma (MM) patients with severe and/or dialysis-dependent renal impairment remains uncertain. We report on the outcomes of 110 patients (median age 57 years) who had become dialysis-dependent pre-ASCT and who underwent a first ASCT between 1997 and 2017. Sixty-three (57%) patients had light chain MM. All patients required dialysis (94% hemodialysis and 6% peritoneal). Forty-four of 71 (62%) patients received bortezomib-based induction regimens and 42 (39%) patients had achieved at least a very good partial response (VGPR) pre-ASCT. Melphalan dosing was as follows: ≤140 mg/m2(82%), and >140 mg/m2(18%). The median PFS after ASCT was 35 months (95% CI: 21.5–42.2) and the median OS 102 months (95% CI: 70.4–129.1). At 1, 2, and 5 years after ASCT, 8% (95% CI 3–14%), 13% (6–20%), and 20% (12–29%) of patients, respectively, had achieved dialysis independence. In multivariate analyses of OS and PFS including age at ASCT, response at ASCT, and year of ASCT, younger age at ASCT and better response at ASCT (CR/VGPR/PR vs. MR/SD/progression) were significantly associated with better OS and PFS.

Objective:Inappropriate handling of cells can generate modifications in the genomic DNA. The additional risk is cross-contamination. Isoenzyme analysis with gel agarose electrophoresis is a known, fast, and cheap technique for detection of species-specific isoforms of intracellular enzymes. The aim of the experimental work was to check if variations in the cell growth conditions can affect morphology and/or nuclear anomalies including micronuclei (MN) in the L929 cells; and to define how sensitive and selective is the classic gel agarose electrophoresis for analysis of isoforms of the selected enzymes to detect cross-contamination of L929 cultures with HeLa cells or with the related species, such as CHO-K1 cells, in the case of unavailability of the commercial kits.Methods:The experiments were done with use of the National Collection of Type Cultures clone 929 (L929)—mouse fibroblasts from subcutaneous connective tissue; HeLa—human cervix adenocarcinoma; and CHO-K1—epithelial-like hamster ovary cells. Cell morphology was evaluated with a light/fluorescence microscope. MN were determined with the cytokinesis-block micronucleus assay, and the isoenzyme analysis was performed using gel agarose electrophoresis.Results:As shown, the overgrown cultures result in a significant increase of the MN in the L929 cells. The band patterns for lactate dehydrogenate, glucose-6-phosphate dehydrogenase, or malate dehydrogenase allow identification of the single L929, HeLa, or CHO-K1 cell line and to detect the cross-contamination, even up to 0.4%.Conclusions:There can be no exceptions from the recommended cell culture conditions in the passage scheme. The sensitivity of the gel agarose separation depends on the cells and on the type of enzyme tested and seems to be sufficient in a quick screening of the CHO-K1, L929, or HeLa cell cultures through the possible mutual contamination.

Allogeneic hematopoietic cell transplantation (allo-HCT) is curative for myelofibrosis (MF) but assessing risk-benefit in individual patients is challenging. This complexity is amplified in CALR-mutated MF patients, as they live longer with conventional treatments compared to other molecular subtypes. We analyzed outcomes of 346 CALR-mutated MF patients who underwent allo-HCT in 123 EBMT centers between 2005 and 2019. After a median follow-up of 40 months, the estimated overall survival (OS) rates at 1, 3, and 5 years were 81%, 71%, and 63%, respectively. Patients receiving busulfan-containing regimens achieved a 5-year OS rate of 71%. Non-relapse mortality (NRM) at 1, 3, and 5 years was 16%, 22%, and 26%, respectively, while the incidence of relapse/progression was 11%, 15%, and 17%, respectively. Multivariate analysis showed that older age correlated with worse OS, while primary MF and HLA mismatched transplants had a near-to-significant trend to decreased OS. Comparative analysis between CALR- and JAK2-mutated MF patients adjusting for confounding factors revealed better OS, lower NRM, lower relapse, and improved graft-versus-host disease-free and relapse-free survival (GRFS) in CALR-mutated patients. These findings confirm the improved prognosis associated with CALRmutation in allo-HCT and support molecular profiling in prognostic scoring systems to predict OS after transplantation in MF.

The optimal conditioning for patients with higher risk MDS receiving potentially curative allogeneic haematopoietic stem cell transplant(allo-HCT) remains to be defined. This is particularly the case for patients with excess of blasts at time of allo-HCT. Sequential (Seq) conditioning, whereby chemotherapy is followed rapidly by transplant conditioning, offers an opportunity to decrease disease burden, potentially improving outcomes allo-HCT outcomes. Herein we present the only analysis comparing Seq to myeloablative (MAC) and reduced intensity conditioning (RIC) specifically focussed on MDS patients with excess of blasts at allo-HCT. 303 patients were identified in the EBMT registry, receiving RIC (n= 158), Seq (n= 105), and MAC (n= 40). Median follow-up was 67.2 months and median age at allo-HCT was 59.5 years (IQR 53.5–65.6). For the entire cohort, 3 y overall survival (OS) was 50% (95% CI 45–56%) and relapse free survival (RFS) 45% (95% CI 40–51%). No significant differences in OS (log-rank p= 0.13) and RFS (log-rank p= 0.18) were observed between conditioning protocols. On multivariable analysis, lower performance status, worse IPSS-R cytogenetics, sibling donor (compared to 8/8 MUD) and ≥20% blasts at allo-HCT were associated with worse outcomes. In conclusion, the Seq protocol did little to influence the outcome in this high-risk group of patients, with outcomes mostly determined by baseline disease risk and patient characteristics such as performance status.

Cocrystallization and coamorphization are similar yet independent approaches toward modifying various pharmaceutically relevant properties of modern drug compounds, in particular, solubility, dissolution rate, and the associated bioavailability. In this work, both strategies were applied to enzalutamide (Enz), a poorly soluble nonsteroidal antiandrogen drug, which led to the development of new multicomponent crystalline and amorphous solid forms of the drug with saccharin (Schr) in a 1:1 molar ratio. The structural analysis of the cocrystal formed by Enz and Schr revealed multiple intermolecular interactions between the components. Both Enz···Enz and Schr···Schr interactions were observed in the crystal packing. With the aid of N–H···O, C–H···O, C–H···N, and C–H···S hydrogen bonds, the molecules were aggregated into a three-dimensional hydrogen-bonded network. In the coamorphous composition, however, the components do not seem to involve in any strong intermolecular interactions and undergo recrystallization separately upon storage at room and elevated temperatures. The thermodynamic solubility of the cocrystal, evaluated using eutectic concentrations of the components, was found to be higher than that of the parent enzalutamide over an entire range of physiological pH values. The advantages and drawbacks of both formulation methods were analyzed and discussed, taking into account a tradeoff between physical stability and dissolution performance of the considered coamorphous composition and the cocrystal.

Lyell’s syndrome, or toxic epidermal necrolysis (TEN) is a rare but life-threatening condition. It manifests with blistering of skin and mucous due to subepidermal bullae and keratinocyte necrosis. In most cases, it is an immune response to drugs or their metabolites. The mortality in TEN is high despite optimal infection and wound control. There are no unequivocal treatment guidelines in TEN. Immunosuppressive treatment may increase the wound infection risk and mortality. The aim of the study was to evaluate a 10-year experience with immunomodulatory therapy in TEN. We perform a combination of plasmapheresis and intravenous immunoglobulins to control the disease. There were 35 patients in the group and we performed a post hoc evaluation. Twenty-eight patients received the full protocol and there were seven patients who did not complete the treatment (single therapy group). The mortality in the test group was 14.29%, and the difference reached statistical significance in comparison with the single therapy group (P< .05). Our protocol reduced the mortality risk five times. Our study proved that simultaneous plasmaphereses with intravenous immunoglobulins administration were safe and improved patients’ outcome in TEN.

Antisense oligonucleotide technology is one of the most successful gene therapy (GT) approaches. However, low selectivity of antisense agents limits their application as anticancer drugs. To achieve activation of antisense agent selectively in cancer cells, herein, we propose the concept of binary antisense oligonucleotide (biASO) agent. biASO recognizes an RNA sequence of a gene associated with cancer development (marker) and then activates RNase H-dependent cleavage of a targeted messenger RNA. biASO was optimized to produce only the background cleavage of the targeted RNA in the absence of the activator. The approach lays the foundation for the development of highly selective and efficient GT agents.

The thermal expansion properties of the Ti6Al4V alloy deposited with direct energy subjected to severe plastic deformation through ECAP were studied in the temperature region 23–700 °C. The deposit samples exhibited two orientations: with the longitudinal axis in the deposition plane and perpendicular to the deposited layers. The microstructure of the deposited alloy and the alloy after thermomechanical treatment was analysed on a scanning electron microscope using the EBSD method. The ECAP process substantially refined the structure of the grains. The temperature dependence of the thermal expansion coefficient estimated for the alloy after ECAP processing exhibited a non-monotonous course. The microstructural changes are the reason for this finding.

The inpatient psychiatric facility prospective payment system (IPF-PPS), provides per diem payments for psychiatric hospitals and units, including 17 comorbid condition payment adjustors that cover 11 percent of patients. This study identifies an alternative set of 16 adjustors identifying three times as many high-cost patients and evaluates the improved predictive power in log per diem cost regression models. A model using the IPF-PPS adjustors achieved 8.8 percent of the feasible improvement from a no-adjustor baseline, while the alternative adjustors achieved 22.1 percent of the feasible improvement. The current adjustors may therefore be too restrictive, resulting in systematic over- or underpayment for many patients., BACKGROUND The Medicare acute inpatient prospective payment system (IPPS) was implemented in 1983 to pay acute care hospitals a per case payment using the diagnosis related groups (DRG). However, psychiatric [...]

Considerable attention has been given to evidence-based process indicators associated with quality of care, while much less attention has been given to the structure and key parameters of the various pay-for-performance (P4P) bonus and penalty arrangements using such measures. In this article we develop a general model of quality payment arrangements and discuss the advantages and disadvantages of the key parameters. We then conduct simulation analyses of four general P4P payment algorithms by varying seven parameters, including indicator weights, indicator inter-correlation, degree of uncertainty regarding intervention effectiveness, and initial baseline rates. Bonuses averaged over several indicators appear insensitive to weighting, correlation, and the number of indicators. The bonuses are sensitive to disease manager perceptions of intervention effectiveness, facing challenging targets, and the use of actual-to-target quality levels versus rates of improvement over baseline., INTRODUCTION The burgeoning research on the sizable geographic variation in surgery rates (Wennberg et al., 1999; Weinstein et al., 2004; 2006), the prevalence of medical errors, and the generally unacceptable [...]

Concern over rapidly rising Medicare expenditures prompted Congress to pass the 1997 Balanced Budget Act (BBA) that included provisions reducing graduate medical education (GME) payments and capped the growth in residents f or payment purposes. Using Medicare cost reports through 2001, we find that both actual and capped residents continued to grow post-BBA. While teaching hospital total margins declined, GME payment reductions of approximately 17 percent had minimal impact on revenue growth (-0.5 percent annually). Four years after BBA, residents remained a substantial line of business for nearly one-half of teaching hospitals with Medicare effective marginal subsidies exceeding resident stipends by nearly $50,000 on average. Coupled with an estimated replacement cost of over $100,000 per resident, it is not surprising that hospitals accepted nearly 4,000 residents beyond their allowable payment caps in just 4 years post-BBA., INTRODUCTION In 1984, Congress passed landmark legislation converting acute general hospitals from cost-based to inpatient prospective payment system (IPPS) payment (Prospective Payment Advisory Commission, 1986). In calibrating the system's payments, [...]

Objective: For a proposed Medicare prospective payment system for inpatient psychiatric facility treatment, the authors developed a casemix classification to capture differences in patients' real daily resource use. Method: Primary data on patient characteristics and daily time spent in various activities were collected in a survey of 696 patients from 40 inpatient psychiatric facilities. Survey data were combined with Medicare claims data to estimate intensity-adjusted daily cost. Classification and Regression Trees (CART) analysis of average daily routine and ancillary costs yielded several hierarchical classification groupings. Regression analysis was used to control for facility and day-of-stay effects in order to compare hierarchical models with models based on the recently proposed payment system of the Centers for Medicare & Medicaid Services. Results: CART analysis identified a small set of patient characteristics strongly associated with higher daily costs, including age, psychiatric diagnosis, deficits in daily living activities, and detox or ECT use. A parsimonious, 16-group, fully interactive model that used five major DSM-IV categories and stratified by age, illness severity, deficits in daily living activities, dangerousness, and use of ECT explained 40% (out of a possible 76%) of daily cost variation not attributable to idiosyncratic daily changes within patients. A noninteractive model based on diagnosis-related groups, age, and medical comorbidity had explanatory power of only 32%. Conclusions: A regression model with 16 casemix groups restricted to using 'appropriate' payment variables (i.e., those with clinical face validity and low administrative burden that are easily validated and provide proper care incentives) produced more efficient and equitable payments than did a noninteractive system based on diagnosis-related groups.

EXECUTIVE SUMMARY * THE VALUE MEASUREMENT AND REPORTING Collaborative (VMRC) is a global effort intended to help boards of directors, senior management, investors and other stakeholders make better strategic decisions [...]

Though the road to fitness is paved with good intentions, it is also littered with abandoned exercise gear, trashed resolutions, and--most disturbingly--the bodies of chubby, out-of-breath folks who fell off [...]

Previous analyses of the costs of Medicare psychiatric inpatients have been limited by the use of claims and provider cost reports that fail to quantify differences in patient characteristics and routine costs. This article uses new primary data from 66 psychiatric inpatient units in 40 facilities nationwide to measure the times staff spend in therapeutic and other activities caring for Medicare patients. Patient days are divided into two groups of very high and low staff intensity and patient characteristics compared in each group. Results identify key patient characteristics associated with high staffing days, including old age, dementia and cognitive impairment, severe psychiatric diagnosis, deficits in activities of daily living (ADLs), and assaultive or agitated behaviors. Policy implications and suggested enhancements are made with regard to the proposed CMS case-mix classification system based on claims data alone., INTRODUCTION Since 1982, psychiatric hospitals and distinct part units (DPUs) of acute general hospitals have been paid under the Tax Equity and Fiscal Responsibility Act (TEFRA) cost-based system. Patients treated [...]

Yes, you're a busy guy: Places to go, people to see, pegs to pump. So when there aren't enough hours in the day to fit it all in, you barrow [...]

Coaxial antennas with properties similar to those of a two-wire dipole antenna are presented and analyzed. Since coaxial antennas extend along a straight line and can have almost any radius, [...]

In humans, MAPK8IP3(also known as JIP3) is a neurodevelopmental disorder-associated gene. In Caenorhabditis elegans, the UNC-16ortholog of the MAPK8IP3 protein can regulate the termination of axon growth. However, its role in this process is not well understood. Here, we report that UNC-16promotes axon termination through a process that includes the LRK-1(LRRK-1/LRRK-2) kinase and the WDFY-3(WDFY3/Alfy) selective autophagy protein. Genetic analysis suggests that UNC-16promotes axon termination through an interaction between its RH1 domain and the dynein complex. Loss of unc-16function causes accumulation of late endosomes specifically in the distal axon. Moreover, we observe synergistic interactions between loss of unc-16function and disruptors of endolysosomal function, indicating that the endolysosomal system promotes axon termination. We also find that the axon termination defects caused by loss of UNC-16function require the function of a genetic pathway that includes lrk-1and wdfy-3, 2 genes that have been implicated in autophagy. These observations suggest a model where UNC-16promotes axon termination by interacting with the endolysosomal system to regulate a pathway that includes LRK-1and WDFY-3.

WE KNOW THEM like we know our own families: The Sopranos mob, Malcolm in the Middle's tribe, Raymond's clan, even the Will & Grace gang. And what with their erratic [...]

I know from experience that inside every out-of-shape woman lies a slim, well-proportioned one. That's why I've designed a program to accentuate the positives and eliminate the negatives of every [...]

Father Time is one heck of an illusionist; he snaps his fingers, and babies are begging for the car keys. He waves his wand, and 2 weeks worth of vacation [...]

At the mall one day, a woman bumps into an old friend and her new baby. Cooing over the stroller, she asks, "How old is he? "Almost a year," says [...]

In this work, four novel pharmaceutical cocrystals of nitrofurantoin, an antibacterial drug, with isonicotinamide, picolinamide, 2-hydroxybenzamide, and 2-aminobenzamide have been obtained and thoroughly characterized by various analytical techniques. The crystal structures of the solid forms have been elucidated by single-crystal X-ray diffraction, and the energy distribution of intermolecular interactions has been further quantified on the basis of QTAIMC analysis. Eight distinct supramolecular heterosynthons of hydrogen bonding have been identified in the studied crystals, and their relative stability has been ranked in terms of total interaction energies. The thermodynamics of the cocrystallization reactions has been systematically investigated using two independent experimental techniques, namely solution calorimetry and phase solubility diagram, which allowed us to assess both the enthalpic and the entropic contributions to the cocrystal formation driving force. The pH-solubility behavior of the cocrystals has been investigated at different pH values using eutectic concentrations of the components. Although all of the cocrystals reported here were found to be more soluble than the parent drug, their advantage in thermodynamic solubility did not translate into enhanced dissolution performance due to a rapid solution-mediated phase transformation in aqueous media. In addition, the effect of cocrystallization on other pharmaceutically relevant properties of nitrofurantoin, including photostability and membrane permeability, has been considered and analyzed.

Autologous hematopoietic cell transplantation (auto-HCT) may be performed in multiple myeloma (MM) patients relapsing after a previous auto-HCT. For those without an adequate dose of stored stem cells, remobilization is necessary. This retrospective study included patients who, following disease relapse after the first auto-HCT(s), underwent stem cell remobilization and auto-HCT performed using these cells. There were 305 patients, 68% male, median age at salvage auto-HCT was 59 years. The median time to relapse after the first-line penultimate auto-HCT(s) was 30.6 months, the median follow-up after salvage auto-HCT 31 months. The 2- and 4-year non-relapse mortality (NRM) after the salvage auto-HCT was 5 and 9%, the relapse incidence 56 and 76%, respectively. Overall survival (OS) after 2 and 4 years was 76 and 52%, progression-free survival (PFS) 39 and 15%. In multivariable analysis an increasing interval between the penultimate auto-HCT and relapse was associated with better OS and PFS, later calendar year of salvage auto-HCT with better OS. In conclusion, salvage auto-HCT performed with cells remobilized after a previous auto-HCT was associated with acceptable NRM. The leading cause of failure was disease progression of MM, which correlated with a shorter interval from the penultimate auto-HCT to the first relapse.

In the mid-fourteenth century a cemetery for the burial of the destitute, pilgrims and non-citizens of Gdańsk, Poland, was founded beyond the city walls. During epidemics, the local urban population was buried there in mass graves. Excavations in Gdańsk led to the discovery of four mass graves, the largest of which contained the remains of 759 people who were probably killed by the same plague. In addition to being used as a plague cemetery, this site also served as a burial ground for criminals. Following a single mass execution, 41 decapitated bodies were interred in a mass grave dated to the fifteenth century. The skulls of these individuals were not found during excavation. Skeletal analysis suggests that the executions may have been performed using a mechanical device: a guillotine.