Contezolid (MRX-I), a new oxazolidinone, is an antibiotic in development for treating complicated skin and soft tissue infections (cSSTI) caused by resistant Gram-positive bacteria. This was a thorough QT study conducted in 52 healthy subjects who were administered oral contezolid at a therapeutic (800 mg) dose, a supratherapeutic (1600 mg) dose, placebo, and oral moxifloxacin 400 mg in 4 separate treatment periods. The pharmacokinetic profile of contezolid was also evaluated. Time-point analysis indicated that the upper bounds of the two-sided 90% confidence interval (CI) for placebo-corrected change-from-baseline QTc (QTc) were <10 ms for the contezolid therapeutic dose at each time point. The upper bound of the 90% CI for QTc were slightly more than 10 ms with the contezolid supratherapeutic dose at 3 and 4 hours postdose, and the prolongation effect on the QT/QTc interval was less than that of the positive control, moxifloxacin 400 mg. At 3 and 4 h after the moxifloxacin dose, the moxifloxacin group met the assay sensitivity criteria outlined in ICH Guidance E14 with having a lower confidence bound ≥5 ms. The results of a linear exposure-response model which were similar to that of a time point analysis demonstrated a slightly positive relationship between contezolid plasma levels and QTcF interval with a slope of 0.227 ms per mg/L (90% CI: 0.188 to 0.266). In summary, contezolid did not prolong the QT interval at a therapeutic dose and may have a slight effect on QT interval prolongation at a supratherapeutic dose.

In vitro and in vivo interactions of minocycline and azoles including itraconazole, voriconazole, and posaconazole against filamentous pathogenic fungi were investigated. A total of 56 clinical isolates were studied in vitro via broth microdilution checkerboard technique, including 20 strains of Aspergillus fumigatus, 7 strains of A. flavus, 16 strains of Exophiala dermatitidis, 10 strains of Fusarium solani and 3 strain s of F. oxysporum. The results revealed that minocycline individually did not exhibit any significant antifungal activity against all tested strains. However, favorable synergy of minocycline with itraconazole, voriconazole, or posaconazole were observed against 34 (61%), 28 (50%), and 38 (69%) isolates, respectively, including azole resistant A. fumigatus and Fusarium spp. with inherently high MICs of azoles. Synergistic combinations resulted in 4 fold to 16-fold reduction of effective MICs of minocycline and azoles. No antagonism was observed. In vivo effect of minocycline-azole combinations were evaluated by survival assay in Galleria mellonella model infected with E. dermatitidis strain BMU00034, F. solani strain FS9, A. fumigatus strain AF293, AFR1 and AFR2 . Minocycline acted synergistically with azoles and significantly increased larvae survival in all isolates (P<0.001), including azole resistant A. fumigatus and azole-inactive Fusarium spp.. In conclusion, the results suggested that minocycline combined with azoles may help to enhance the antifungal susceptibilities of azoles against pathogenic fungi and had the potential to overcome azole resistance issues.

Background: MRSA pose significant therapeutic challenges, related to their: frequency in clinical infections; innate virulence properties; and propensity for multi-antibiotic resistance. MRSA are among the most common causes of endovascular infections, including infective endocarditis (IE).

Objective: To employ transthoracic echocardiography (TTE) to evaluate the effect of exebacase, a novel direct lytic agent, in experimental aortic valve MRSA IE.

Study Design: TTE was utilized to evaluate the in vivo effect of exebacase on MRSA-infected vegetation progression when combined with daptomycin (vs daptomycin alone). Primary intravegetation outcomes were: maximum size; weights at sacrifice; and MRSA counts at infection baseline vs after 4 days of daptomycin treatment (alone or in addition to exebacase administered once on treatment Day 1).

Results: A single dose of exebacase in addition to daptomycin cleared significantly more intravegetation MRSA than daptomycin alone. This was associated with a statistical trend toward reduced maximum vegetation size in the exebacase + daptomycin vs the daptomycin-alone therapy groups (p = 0.07). Also, mean vegetation weights in the exebacase-treated group were significantly lower vs daptomycin-alone (p < 0.0001). Maximum vegetation size by TTE correlated with vegetation weight (p = 0.005). In addition, intravegetation MRSA counts in the combination group were significantly lower vs untreated controls (p<0.0001) and the daptomycin-alone group (p<0.0001).

Conclusion: This study suggests that exebacase has a salutary impact on MRSA-infected vegetation progression when combined with daptomycin, especially in terms of vegetation MRSA burden, size and weight. Moreover, TTE appears to be an efficient non-invasive tool to assess therapeutic efficacies in experimental MRSA IE.

The Penn State Smeal College of Business Center for the Business of Sustainability recently hosted the first in a series of virtual fireside discussions titled “The Impact of Coronavirus on Sustainability and Social Impact,” to explore how recent momentum in sustainability efforts has been altered.

A new Council of the Great City Schools effort aims to fill in a training gap for an important constituency: school boards.

CONTEXT:

Pneumococcal conjugate vaccines (PCVs) (pneumococcal 13-valent conjugate vaccine [PCV-13] and pneumococcal 10-valent conjugate vaccine [PCV-10]) are available for prevention of pneumococcal infections in children.

If researchers hope to identify programs that will prepare students for the future, then they cannot continue to measure innovation based on the ideas from the past.

Zoom-bombings have been making headlines across the country this spring, and Penn State is no exception to the increase in security threats and breaches. To address these recent incidents in Zoom meetings, University-wide Zoom default setting changes will be implemented on May 11.

Now we're typing with scan lines!

The reason young people fail to vote is not because they don't care about politics or policy, but because they don't know how to translate their ideals into action, a new book argues.

Governor Markell announced on Friday that Delaware has effectively ended veteran homelessness, receiving certification last month from the United States Interagency Council on Homelessness, the U.S. Department of Housing and Urban Development and the U.S. Department of Veterans Affairs.

Researchers in Penn State’s College of Engineering, College of Agricultural Sciences and College of Medicine say direct LTP treatment and plasma-activated media are effective treatments against bacteria found in liquid cultures and have devised a way to create plasma directly in liquids.

An experimental drug has proved effective against the new coronavirus in a major study, shortening the time it takes for patients to recover by four days on average, U.

Alireza Mansouri and Fattaneh Taghiyareh: Human interactions and opinion exchanges lead to social opinion dynamics, which is well described by opinion formation models. In these models, a random parameter is usually considered as the system noise, indicating the individual's inexplicable opinion changes. This noise could be an indicator of any other influential factors, such as public media, affects, and emotions. We study phase transitions, changes from one social phase to another, for various noise levels in a discrete opinion formation model based on the social impact theory with a scale-free random network as its interaction network topology. We also generate another similar model using the concept of social power based on the agents' node degrees in the interaction network as an estimation for their persuasiveness and supportiveness strengths and compare both models from phase transition viewpoint. We show by agent-based simulation and analytical considerations how opinion phases, including majority and non-majority, are formed in terms of the initial population of agents in opinion groups and noise levels. Two factors affect the system phase in equilibrium when the noise level increases: breaking up more segregated groups and dominance of stochastic behavior of the agents on their deterministic behavior. In the high enough noise levels, the system reaches a non-majority phase in equilibrium, regardless of the initial combination of opinion groups. In relatively low noise levels, the original model and the model whose agents' strengths are proportional to their centrality have different behaviors. The presence of a few high-connected influential leaders in the latter model consequences a different behavior in reaching equilibrium phase and different thresholds of noise levels for phase transitions.

 Exchange Rate notification for Import / Export of goods with effect from 1st October, 2010

 Amends Notification

The Hon’ble court after observing reports given by various technical authorities like the Varadharajan Committee and The Central Board for the prevention and Control of Water Pollution, held that the emissions generated by the coke/coal consuming industries are air-pollutants and have a damaging effect on the Taj and the people living in TTZ. The court directed the atmospheric pollution generated in TTZ to be eliminated and the industries to use natural gas as an industrial fuel and those industries who are not in a position to obtain gas connections to relocate themselves.

Wilmington --

Due to the presence of Coronavirus (COVID-19) in Delaware, business closures, reductions in staffing and lower ridership levels, effective Wednesday, March 18, DART public transit services will operate on the following reduced service schedule until further notice. On weekdays, regular fixed route services will operate on a Saturday service schedule statewide, with additional service on Routes 15, 18, 43 and 301. DART's regularly scheduled weekend service will operate normal service levels. [More]

Social media use surges; average time spent on platforms like Facebook and Instagram up by over 60%.

The EPFO’s decision to extend the due date for filing is expected to benefit about six lakh establishments, including four lakh establishments eligible under the Pradhan Mantri Garib Kalyan Yojana (PMGKY) package.

As credit risk funds may see redemption pressure because there are no takers for lower-rated paper, investors can opt for liquid and overnight funds.

The next two months will be weak and slowdown in Ulips to continue for the rest of the year

Reduce your debts, cut expenses and choose investment products prudently to build your retirement corpus.

Guleria said inhalation and ingestion of styrene can cause effect the skin and the eyes.

Coronavirus, COVID 19 latest news: The revelation has been made in a study published in the Canadian Medical Association Journal. The study looked at 144 geopolitical areas. These areas include large swathes of the US, Canada, Australia, and other countries around the world.

The central nervous system is affected by exposure to styrene smoke. It is the mucous membrane, which is primarily affected by styrene gas exposure. The styrene gas leak in Visakhapatnam triggered acute breathlessness among many men, some of whom were asphyxiated to death.

The threat for global warming is increasing in this world with each passing day. It is not a distant future when the effects of the global warming will hit hard the lives of the human. However, seeing the future threat Denmark has braced itself with…

What if you suspect something is wrong with your forecasting process? What if the process is consuming too much time and too many resources, while still delivering unsatisfactory results (lousy forecasts). What can you do about it? This post looks at the first two steps to effecting meaningful forecasting process [...]

The post 2 first steps to effecting forecasting process change appeared first on The Business Forecasting Deal.

Two weeks ago we looked at the first two steps in effecting forecasting process change: Justify your suspicions with data Communicate your findings That was the easy part. So why is it that so many organization realize they have a forecasting problem, yet are unable to do anything about it? [...]

The post The difficult step in effecting forecasting process change (1 of 2) appeared first on The Business Forecasting Deal.

Fildes and Goodwin (F&G) observed the subject (the regional subsidiary of a pharmaceutical company) was using a statistical forecasting system, but not fully trusting its output. Forecasters were making overrides to the system generated forecast to make it look like what they believed it should (e.g., following a life-cycle curve [...]

The post The difficult step in effecting forecasting process change (2 of 2) appeared first on The Business Forecasting Deal.

  Google recently unveiled a huge makeover to its Google Maps. Currently available in beta mode, it lets you discover changes in its interface and improved accessibilities. However, the search results i...

'New type of analysis' deployed to determine plastics' toxicity

Clearer scope and guidance document needed, says CII

Among the possibilities, the government could garner some revenues from sale of the BPCL’s 61% stake sale in Numaligarh Refinery, which will be sold to state-run firms.

Mills in Uttar Pradesh have produced 11.65 MT as on April 30, 2020, which is 3.72 lakh tonne higher than what was produced a year ago. Of 119 mills operated this year, 44 mills have ended their crushing. As many as 75 mills are operating as against 68 mills last year till April 30.

State governments seem to have collected the lowest-ever inflation-adjusted monthly tax revenue in April.

With the countrywide lockdown set to continue for two more weeks, banks have urged the Reserve Bank of India (RBI) to extend the three-month moratorium on loans by another three months beyond May 31.

The Union Home Ministry said that in an order under the Disaster Management Act, “Directions were issued that district and state borders should be effectively sealed. States were directed to ensure there is no movement of people across cities or on highways.”

In continuation of the travel advisory issued on March 11 and March 16, the following additional advisory has been issued.

Kotak Mahindra Bank, which has revised interest rate on daily balances in savings account multiple times over the past year or so, has again made a change.

The percentage of applicants is in low single digit as a share of the loan book, the bank said, but this could go up as it has not put a deadline or a cut-off for people to apply.

The development also shows the government's push for digital technology has enabled people to access banking services even when the pandemic spread its tentacles.

Google has already rolled out a few updates to Duo since the COVID-19 pandemic hit. Since video chat is more important than ever, Google is making Duo a priority, bring its video chat up to parity with its biggest competitors.This latest update packs in new AR effects which always make video calls a bit more ...

In this blog, I will brief you about two very useful Rapid Adoption Kits (RAKs) for Liberate LV Library Validation.(read more)

કોરોનાને કારણે બિલ્ડરોને પ્રોજેક્ટ પૂરા કરવામાં વધારે સમય લાગશે, લોકોને સમયસર પઝેશન નહીં મળી શકે.

This Metasploit module exploits an issue in Google Chrome version 80.0.3987.87 (64 bit). The exploit corrupts the length of a float array (float_rel), which can then be used for out of bounds read and write on adjacent memory. The relative read and write is then used to modify a UInt64Array (uint64_aarw) which is used for read and writing from absolute memory. The exploit then uses WebAssembly in order to allocate a region of RWX memory, which is then replaced with the payload shellcode. The payload is executed within the sandboxed renderer process, so the browser must be run with the --no-sandbox option for the payload to work correctly.