Clinical outcome and drug expenses of intravitreal therapy for diabetic macular edema: A retrospective study in Sardinia, Italy

Background: Diabetic macular edema (DME) is a leading cause of visual loss in working-age adults. The purpose of this retrospective study was to perform an epidemiological analysis on DME patients treated with intravitreal drugs in a tertiary hospital. The clinical outcome, adverse drug reactions (ADRs), and intravitreal drug expenses were assessed. Methods: All DME patients treated with Ranibizumab, Aflibercept, Dexamethasone implant, and Fluocinolone Acetonide implant at the Sassari University Hospital, Italy, between January 2017 and June 2020 were included. Central macular thickness (CMT) and best corrected visual acuity (BCVA) were measured. ADRs and drug expenses were analyzed. Results: Two-hundred thirty-one DME patients (mean age: 65 years) received intravitreal agents. Mean CMT and BCVA were 380 μm and 0.5 LogMAR at baseline, 298 μm and 0.44 logMAR after one year (p = 0.04), and 295 μm and 0.4 logMAR at the end of the follow-up period. A total of 1501 intravitreal injections were given; no major ADRs were reported. Treatment cost was €915,000 (€261,429/year). Twenty non-responders to Ranibizumab or Afliber-cept were switched to a Dexamethasone implant. In these patients, mean CMT and BCVA were 468 µm and 0.5 LogMar at the time of switching and 362 µm and 0.3 LogMar at the end of the follow-up (p = 0.00014 and p = 0.08, respectively). Conclusion: Results confirm that Ranibizumab, Afliber-cept, and Dexamethasone implant are effective and safe in DME treatment. A switch to Dexame-thasone implant for patients receiving Aflibercept or Ranibizumab with minimal/no clinical benefit should be considered

Vitellogenin Dynamics and Reproductive Morphology at Sexual Maturity of Philippine Mallard (Anas Platyrhynchos Domesticus L) Fed with Zinc Supplemented Diet

The vitellogenin (Vtg) is a precursor for the synthesis of egg yolk protein. Feeding with zinc-supplemented diet is hypothesized to increase the circulating Vtg thereby enhancing reproductive development. A total of 80 ducks,aged 16 weeks old, were randomly assigned to treatment groups; namely: group A with 40 ducks fed with 30 ppm zinc-supplemented diet (zinc positive) and group B with 40 ducks fed with no added zinc (zinc negative). Thecirculating Vtg at sexual maturity (155.11±10.83 days old) were determined from the blood sera. The sera were assayed for Vtg in duplicate using 96–well microplate and read the optical density at 415nm. The zinc concentrationof the samples was calculated using the nonlinear regression =OD = a x [Zn2+] / (b + [Zn2+]. Results show that the circulating Vtg in the blood sera of ducks at sexual maturity were 0.69±0.07 Gg Zn dL-1. The feeding of zinc-treateddiet had no significant influenced on the concentration of circulating Vtg. There was also insignificant difference in the reproductive morphology of ducks fed with or without added zinc. The Vtg concentration had no correlation withreproductive parameters but found to be positively correlated with liver weight (H=0.21) and negatively correlated with body weight (H = -0.24)

Cosmological Parameters Degeneracies and Non-Gaussian Halo Bias

We study the impact of the cosmological parameters uncertainties on the measurements of primordial non-Gaussianity through the large-scale non-Gaussian halo bias effect. While this is not expected to be an issue for the standard LCDM model, it may not be the case for more general models that modify the large-scale shape of the power spectrum. We consider the so-called local non-Gaussianity model and forecasts from planned surveys, alone and combined with a Planck CMB prior. In particular, we consider EUCLID- and LSST-like surveys and forecast the correlations among $f_{\rm NL}$ and the running of the spectral index $\alpha_s$, the dark energy equation of state $w$, the effective sound speed of dark energy perturbations $c^2_s$, the total mass of massive neutrinos $M_\nu=\sum m_\nu$, and the number of extra relativistic degrees of freedom $N_\nu^{rel}$. Neglecting CMB information on $f_{\rm NL}$ and scales $k > 0.03 h$/Mpc, we find that, if $N_\nu^{\rm rel}$ is assumed to be known, the uncertainty on cosmological parameters increases the error on $f_{\rm NL}$ by 10 to 30% depending on the survey. Thus the $f_{\rm NL}$ constraint is remarkable robust to cosmological model uncertainties. On the other hand, if $N_\nu^{\rm rel}$ is simultaneously constrained from the data, the $f_{\rm NL}$ error increases by $\sim 80$. Finally, future surveys which provide a large sample of galaxies or galaxy clusters over a volume comparable to the Hubble volume can measure primordial non-Gaussianity of the local form with a marginalized 1--$\sigma$ error of the order $\Delta f_{\rm NL} \sim 2-5$, after combination with CMB priors for the remaining cosmological parameters. These results are competitive with CMB bispectrum constraints achievable with an ideal CMB experiment.Comment: 17 pages, 1 figure added, typos corrected, comments added, matches the published versio

Товарно-материальные запасы и финансовые показатели промышленных индонезийских и немецких компаний, зарегистрированных на бирже

Inventory management is a fundamental supply chain management phase that affects the country’s economy.The purpose of the study is to determine the effectiveness of inventory management and its impact on the financial performance in the factoring industry, as it has become one of the leading sectors in boosting the development of the national economy.Descriptive and quantitative methods were used, which mainly relied on financial data for 2013–2017 on the selected publicly listed manufacturing companies in Indonesia and Germany based on the LQ45 and DAX stock index, respectively. Several software programs (Microsoft Excel, SPSS, and AMOS) were used for solving the inventory-financial performance and value analysis based on Structural Equation Modeling.The results of the study confirm that inventory performance significantly influences financial performance, as the p-value is below 5%. Inventory performance has an explanatory power of 30.6% for financial performance. An increase in inventory performance will increase financial performance as well. Each indicator has an explanatory power of DSI (101.2%), INVTO (96.4%), FGI (63.3%), WIP (58.3%), and RMI (51.7%) towards inventory performance, which will increase performance as well. For financial performance, each indicator has an explanatory power of ROIC (97.0%); ROE (85.1%); ROA (76.9%); GR (46.7%); PM (5.6%), and OM (5.3%) towards financial performance, which will also contribute to improved efficiency.Управление товарными запасами является одним из основных звеньев менеджмента в цепочке поставок, влияющим на экономику страны.Цель исследования —  определить эффективность управления запасами и его влияние на финансовые показатели факторинговой отрасли, которая стала одним из ведущих секторов, способствующих развитию национальной экономики. Использованы описательный и количественный методы, которые в основном опирались на финансовые данные за 2013–2017 гг. по выбранным публично зарегистрированным производственным компаниям в Индонезии и Германии на основе фондового индекса LQ45 и DAX соответственно. Для анализа финансовой эффективности и стоимости запасов на основе моделирования структурных уравнений использовалось несколько программных продуктов (Microsoft Excel, SPSS и AMOS). Результаты исследования подтверждают, что эффективность использования товарно-материальных запасов существенно влияет на финансовые результаты, так как p-значение ниже 5%. Объясняющая способность показателей товарно-материальных запасов по отношению к финансовым результатам составляет 30,6%. Повышение эффективности использования запасов приведет к росту финансовых показателей. Объясняющая способность каждого показателя DSI (101,2%), INVTO (96,4%), FGI (63,3%), WIP (58,3%) и RMI (51,7%) по отношению к показателям товарно-материальных запасов также приведет к росту эффективности. Для финансовых результатов каждый показатель имеет объясняющую способность ROIC (97,0%), ROE (85,1%), ROA (76,9%), GR (46,7%), PM (5,6%) и OM (5,3%) по отношению к финансовым результатам, что также будет способствовать повышению эффективности

Histochemical Evaluation of Human Prostatic Tissues with Cratylia mollis Seed Lectin

Lectins, proteins which selectively recognize carbohydrates, have been used in histochemistry for the evaluation of changes in glycosylation in processes of cellular differentiation and/or dedifferentiation. Cratylia mollis seed lectins (Cramoll 1,4 and Cramoll 3), conjugated to horseradish peroxidase, were used as histochemical probes in human prostate tissues: normal (NP), hyperplasia (BPH), and prostate carcinoma (PCa). The staining pattern of Con-A and Cramoll 1,4 in BPH was more intense than in NP. These lectins also showed staining differences between BPH and PCa; the latter showing decreased staining intensity with an increased degree of malignancy. PNA and Cramoll 3 stained epithelial cells similarly in all diagnoses although they did present intense staining of PCa glands lumen. Corpora amylacea were not differentially recognized by any of the lectins. Cramoll 1,4 and Cramoll 3 seed lectins present themselves as candidates for histochemical probes for prostate pathologies when compared to commercial lectins such as Con-A and PNA

Collaborative Development of Clinical Trials Education Programs for African-American Community-Based Organizations

This paper describes the use of a unique ”Learning and Feedback” approach to tailor cancer clinical trials education programs for Community Bridges, a peer training intervention designed for African American communities in North Carolina. Generic community education modules were demonstrated with key community leaders who were designated as trainers. Quantitative and qualitative assessments were provided on understanding of content, comfort with material and cultural relevance. The generic materials were adapted into three revised modules, all featuring key messages about cancer clinical trials, discussion regarding distrust of medical research, common misconceptions about trials, patient protections, and a call to action to prompt increased inquiry about locally available trials. The revised modules were then used as part of a train-the-trainer program with 12 African American community leaders. ENACCT’s use of the Learning and Feedback process is an innovative method for culturally adapting clinical trials education

Proteinuria as a modifiable risk factor for the progression of non-diabetic renal disease

Proteinuria as a modifiable risk factor for the progression of non-diabetic renal disease.BackgroundAngiotensin-converting enzyme (ACE) inhibitors reduce urine protein excretion and slow the progression of renal disease. The beneficial effect in slowing the progression of renal disease is greater in patients with higher urine protein excretion at the onset of treatment. We hypothesized that the greater beneficial effect of ACE inhibitors on the progression of renal disease in patients with higher baseline levels of proteinuria is due to their greater antiproteinuric effect in these patients.MethodsData were analyzed from 1860 patients enrolled in 11 randomized controlled trials comparing the effect of antihypertensive regimens, including ACE inhibitors to regimens not including ACE inhibitors on the progression of non-diabetic renal disease. Multivariable linear regression analysis was used to assess the relationship between the level of proteinuria at baseline and changes in urine protein excretion during follow-up. The Cox proportional hazards analysis was used to assess the relationship between changes in urine protein excretion during follow-up and the effect of ACE inhibitors on the time to doubling of baseline serum creatinine values or onset of end-stage renal disease.ResultsMean (median) baseline urine protein excretion was 1.8 (0.94) g/day. Patients with higher baseline urine protein excretion values had a greater reduction in proteinuria during the follow-up in association with treatment with ACE inhibitors and in association with lowering systolic and diastolic blood pressures (interaction P < 0.001 for all). A higher level of urine protein excretion during follow-up (baseline minus change) was associated with a greater risk of progression [relative risk 5.56 (3.87 to 7.98) for each 1.0 g/day higher protein excretion]. After controlling for the current level of urine protein excretion, the beneficial effect of ACE inhibitors remained significant [relative risk for ACE inhibitors vs. control was 0.66 (0.52 to 0.83)], but there was no significant interaction between the beneficial effect of ACE inhibitors and the baseline level of urine protein excretion.ConclusionsThe antiproteinuric effects of ACE inhibitors and lowering blood pressure are greater in patients with a higher baseline urine protein excretion. The greater beneficial effect of ACE inhibitors on renal disease progression in patients with higher baseline proteinuria can be explained by their greater antiproteinuric effects in these patients. The current level of urine protein excretion is a modifiable risk factor for the progression of non-diabetic renal disease. ACE inhibitors provide greater beneficial effect at all levels of current urine protein excretion

Evidence of Aquaporin 4 Regulation by Thyroid Hormone During Mouse Brain Development and in Cultured Human Glioblastoma Multiforme Cells

Accumulating evidence indicates that thyroid function and the thyroid hormones L-thyroxine (T4) and L-triiodothyronine (T3) are important factors contributing to the improvement of various pathologies of the central nervous system, including stroke, and various types of cancer, including glioblastoma multiforme (GBM). Low levels of T3 are correlated with the poorest outcome of post-stroke brain function, as well as an increased migration and proliferation of GBM tumor cells. Thyroid hormones are known to stimulate maturation and brain development. Aquaporin 4 (AQP4) is a key factor mediating the cell swelling and edema that occurs during ischemic stroke, and plays a potential role in the migration and proliferation of GBM tumor cells. In this study, as a possible therapeutic target for GBM, we investigated the potential role of T3 in the expression of AQP4 during different stages of mouse brain development. Pregnant mice at gestational day 18, or young animals at postnatal days 27 and 57, received injection of T3 (1 μg/g) or NaOH (0.02 N vehicle). The brains of mice sacrificed on postnatal days 0, 30, and 60 were perfused with 4% paraformaldehyde and sections were prepared for immunohistochemistry of AQP4. AQP4 immunofluorescence was measured in the mouse brains and human GBM cell lines. We found that distribution of AQP4 was localized in astrocytes of the periventricular, subpial, and cerebral parenchyma. Newborn mice treated with T3 showed a significant decrease in AQP4 immunoreactivity followed by an increased expression at P30 and a subsequent stabilization of aquaporin levels in adulthood. All GBM cell lines examined exhibited significantly lower AQP4 expression than cultured astrocytes. T3 treatment significantly downregulated AQP4 in GBM-95 cells but did not influence the rate of GBM cell migration measured 24 h after treatment initiation. Collectively, our results showed that AQP4 expression is developmentally regulated by T3 in astrocytes of the cerebral cortex of newborn and young mice, and is discretely downregulated in GBM cells. These findings indicate that higher concentrations of T3 thyroid hormone would be more suitable for reducing AQP4 in GBM tumorigenic cells, thereby resulting in better outcomes regarding the reduction of brain tumor cell migration and proliferation

Measuring the neutrino mass from future wide galaxy cluster catalogues

We present forecast errors on a wide range of cosmological parameters obtained from a photometric cluster catalogue of a future wide-field Euclid-like survey. We focus in particular on the total neutrino mass as constrained by a combination of the galaxy cluster number counts and correlation function. For the latter we consider only the shape information and the Baryon Acoustic Oscillations (BAO), while marginalising over the spectral amplitude and the redshift space distortions. In addition to the cosmological parameters of the standard LCDM+nu model we also consider a non-vanishing curvature, and two parameters describing a redshift evolution for the dark energy equation of state. For completeness, we also marginalise over a set of "nuisance" parameters, representing the uncertainties on the cluster mass determination. We find that combining cluster counts with power spectrum information greatly improves the constraining power of each probe taken individually, with errors on cosmological parameters being reduced by up to an order of magnitude. In particular, the best improvements are for the parameters defining the dynamical evolution of dark energy, where cluster counts break degeneracies. Moreover, the resulting error on neutrino mass is at the level of \sigma(M_\nu)\sim 0.9 eV, comparable with that derived from present Ly-alpha forest measurements and Cosmic Microwave background (CMB) data in the framework of a non-flat Universe. Further adopting Planck priors and reducing the number of free parameters to a LCDM+nu cosmology allows to place constraints on the total neutrino mass of \sigma(M_\nu) \sim 0.08 eV, close to the lower bound enforced by neutrino oscillation experiments. [abridged]Comment: 25 pages, 2 figures, 2 tables, matches the JCAP accepted versio

Euclid: Constraining ensemble photometric redshift distributions with stacked spectroscopy

The ESA Euclid mission will produce photometric galaxy samples over 15000 square degrees of the sky that will be rich for clustering and weak lensing statistics. The accuracy of the cosmological constraints derived from these measurements will depend on the knowledge of the underlying redshift distributions based on photometric redshift calibrations. A new approach is proposed to use the stacked spectra from Euclid slitless spectroscopy to augment broad-band photometric information to constrain the redshift distribution with spectral energy distribution fitting. The high spectral resolution available in the stacked spectra complements the photometry and helps to break the colour-redshift degeneracy and constrain the redshift distribution of galaxy samples. We modelled the stacked spectra as a linear mixture of spectral templates. The mixture may be inverted to infer the underlying redshift distribution using constrained regression algorithms. We demonstrate the method on simulated Vera C. Rubin Observatory and Euclid mock survey data sets based on the Euclid Flagship mock galaxy catalogue. We assess the accuracy of the reconstruction by considering the inference of the baryon acoustic scale from angular two-point correlation function measurements. We selected mock photometric galaxy samples at redshift z>1 using the self-organising map algorithm. Considering the idealised case without dust attenuation, we find that the redshift distributions of these samples can be recovered with 0.5% accuracy on the baryon acoustic scale. The estimates are not significantly degraded by the spectroscopic measurement noise due to the large sample size. However, the error degrades to 2% when the dust attenuation model is left free. We find that the colour degeneracies introduced by attenuation limit the accuracy considering the wavelength coverage of Euclid near-infrared spectroscopy