Educators are wrestling with tough questions as more schools embrace personalized learning and its accompanying belief in giving students more control over their academic experiences.

Education Week takes a close look at the obstacles and opportunities for American Indian children in finding success in school and beyond.

Valor Collegiate Academies has been in the top 5 percent of Tennessee schools on growth and achievement every year since it started in 2014. But Tom visited Valor because of the well-regarded Valor Compass, a holistic human-development program.

Countries that score highest on an international measure of student achievement tend to have these three things in common when it comes to professional development for teachers.

Allon Raiz is CEO of business incubator Raizcorp. In this series of articles, he offers entrepreneurs advice on surviving a crisis.

Now, more than ever, we need to be listening for market signals and ensuring that our businesses are primed to both take advantage of opportunities and to mitigate risks, says Allon Raiz.

La fièvre des élections s’empare de l’Afrique centrale. Pour la seconde fois depuis la fin des guerres qui ont dévasté la région, les scrutins s’enchaînent au Burundi, au Rwanda, en République centrafricaine et au Congo.

Election fever has spread across Central Africa. For the second time since the end of the disastrous civil wars in the region, electoral processes have been launched in Burundi, Rwanda, Central African Republic and the Congo.

Vu du centre de l’Afrique – Tchad, République centrafricaine (RCA) et RD Congo –, le cinquantenaire des indépendances est un anniversaire à l’envers : on en parle davantage à Paris et Bruxelles qu’à N’Djamena, Bangui et Kinshasa. Sans doute parce que, en Europe, il s’agit avant tout de gérer des diasporas turbulentes et une relation bilatérale devenue épineuse tandis que, dans les capitales africaines, il s’agit d’éviter à tout prix le droit d’inventaire.

Dans de nombreux pays, le pétrole suscite des débats controversés sur son rôle de moteur de changements économiques, sociaux et géopolitiques. Depuis quelques années, les réflexions sur la question du pétrole ont démontré une corrélation négative entre son exploitation, le développement socioéconomique, la gouvernance et le regain des conflits dans les pays producteurs.

Extreme poverty and armed conflict in the diamond-rich areas of the Central African Republic (CAR) put thousands of lives in danger and demand urgent reform of the mining sector.

The international watchdog which seeks to prevent diamonds from fuelling conflict, the Kimberley Process, should take a very close look at the situation in the Central African Republic

Le processus électoral hors délai constitutionnel qui se déroule depuis le 23 janvier en Centrafrique n'est pas seulement une nouvelle opportunité manquée pour la démocratisation du pays mais c'est aussi un risque sérieux pour la paix.

More than a decade after the Economic Community of Central African States (ECCAS) was requested by the African Union (AU) to give life to a new peace and security architecture, political and security cooperation on the continent is still in need of reinforcement.

La rechute est le risque majeur des pays post-conflit et l'une des principales raisons de cette rechute s'appelle la corruption.

The collapse of the state and the disappearance of security forces from a large part of the territory may turn the Central African Republic (CAR) into a source of instability in the heart of Africa.
Please note the full report is only available in French.

All this foreign involvement has failed to prevent the recent coup or stabilize its aftermath. BINUCA has not been able to implement a disarmament, demobilisation and reintegration program, and it failed to convince Bozizé’s regime to reform the security sector or consolidate the peace. ECCAS has been unable to restore order in one of the smallest capitals of Africa, and troop-contributing countries have proved unable to deliver the 600 extra soldiers they committed to provide in April. Paradoxically, France, while securing Bangui’s airport, is also hosting ousted president Bozizé, who declared from exile in Paris his wish to retake power by force with the “support” of private actors.

L’indifférence internationale est un facteur aggravant pour les conflits dans les petits pays. Cependant, en ce qui concerne la République centrafricaine (RCA), le contexte est paradoxalement différent.

Since the March 24 coup by the Seleka, a loose coalition of Muslim rebels, the Central African Republic has been in free fall. There are about 400,000 internally displaced people, 64,000 refugees, and burned villages, largely in the western part of the country. Banditry, the rise of self-defense militias and clashes between Christian and Muslim communities are now part of daily life for this mineral-rich country in the heart of Africa. The expanding insecurity makes the delivery of humanitarian assistance difficult, and the United Nations has even warned of the risk of genocide.

Los conflictos en los países pequeños suelen agravarse debido a la indiferencia internacional. Sin embargo, en el caso de la República Centroafricana (RCA), el problema es ligeramente distinto. Hay una importante presencia internacional en este Estado, pero los actores principales han decidido mantenerse al margen y esperar en vez de intervenir activamente en la crisis.

As the Central African Republic (CAR) stares into an abyss of potentially appalling proportions, the international community must focus on the quickest, most decisive means of restoring security to its population.

By failing to engage when Crisis Group and others warned that the Central African Republic had become a phantom state, the international community has now had to become much more heavily involved, at much greater expense, after horrifying loss of life and massive displacement, with much greater odds of failure.

Incapable d’agir quand Crisis Group et d’autres organisations envoyaient des signaux d’alerte et qualifiaient la Centrafrique d’Etat fantôme, la communauté internationale doit dorénavant s’impliquer massivement, à des coûts largement supérieurs, suite aux pertes humaines considérables et aux déplacements massifs de population, et avec des chances de succès beaucoup plus faibles.

Sensible, inclusive regulation of pastoralism that has mitigated tension in parts of the Sahel should be extended to the Democratic Republic of Congo (DRC) and the Central African Republic (CAR), where conflicts have worsened with the southward expansion of pastoralism.

The United Nations Security Council decided on 10 April to deploy a peacekeeping mission in the Central African Republic (CAR) which will take over the mission of the African Union (MISCA), which itself succeeded the mission of the Economic Community of Central African States (MICOPAX).

To stabilise the Central African Republic (CAR), the transitional government and its international partners need to prioritise, alongside security, action to fight corruption and trafficking of natural resources, as well as revive the economy.

In Central African Republic, the conflict between armed groups is now compounded by a conflict between armed communities. The roadmap to end the crisis including elections late 2015 presents only a short-term answer and risks exacerbating existing tensions. The transitional authorities and their international partners must address crucial issues by implementing a comprehensive disarmament policy and reaffirming that Muslims belong within the nation.

En Centrafrique, la course aux élections qui prévoit des scrutins présidentiel et législatif avant la fin de l’année est aussi irréaliste que dangereuse. Alors que le plan initial de la transition a complètement déraillé, l’obstination des internationaux, et plus particulièrement de la France, à faire voter les Centrafricains à l’ombre des groupes armés, avec une administration territoriale squelettique et des haines inter-communautaires tenaces ressemble plus à une fuite en avant qu’à un processus de transition accompli.

Carbapenems are currently the preferred agents for the treatment of serious Acinetobacter infections. However, whether cefepime/cefpirome can be used to treat Acinetobacter bloodstream infection (BSI) if it is active against the causative pathogens is not clear. This study aimed to compare the efficacy of cefepime/cefpirome and carbapenem monotherapy in patients with Acinetobacter BSI. The population included 360 patients with monomicrobial Acinetobacter BSI receiving appropriate antimicrobial therapy admitted to four medical centres in Taiwan in 2012–2017. The predictors of 30-day mortality were determined by Cox regression analysis. The overall 30-day mortality rate in the appropriate antibiotic treatment group was 25.0% (90/360 patients), respectively. The crude 30-day mortality rates for cefepime/cefpirome and carbapenem therapy were 11.5% (7/61 patients) and 26.3% (21/80 patients), respectively. The patients receiving cefepime/cefpirome/carbapenem therapy were infected by Acinetobacter nosocomialis (51.8%), A. baumannii (18.4%) and A. pittii (12.1%). After adjusting for age, Sequential Organ Failure Assessment (SOFA) score, invasive procedures, and underlying diseases, cefepime/cefpirome therapy was not independently associated with a higher or lower 30-day mortality compared to the carbapenem therapy. SOFA score (hazard ratio [HR], 1.324; 95% confidence interval [CI], 1.137–1.543; P < 0.001) and neutropenia (HR, 7.060; 95% CI, 1.607–31.019; P = 0.010) were independent risk factors for 30-day mortality of patients receiving cefepime/cefpirome or carbapenem monotherapy. The incidence density of 30-day mortality for cefepime/cefpirome versus carbapenem therapy was 0.40% versus 1.04%. The therapeutic response of cefepime/cefpirome therapy was comparable to that of carbapenems among patients with Acinetobacter BSI receiving appropriate antimicrobial therapy.

QPX7728 is an ultra-broad-spectrum boronic acid beta-lactamase inhibitor that demonstrates inhibition of key serine and metallo beta-lactamases at a nano molar range in biochemical assays with purified enzymes. The broad-spectrum inhibitory activity of QPX7728 observed in biochemical experiments translates into enhancement of the potency of many beta-lactams against strains of target pathogens producing beta-lactamases. The impact of bacterial efflux and permeability on inhibitory potency were determined using isogenic panels of KPC-3 producing isogenic strains of K. pneumoniae and P. aeruginosa and OXA-23-producing strains of A. baumannii with various combinations of efflux and porin mutations. QPX7728 was minimally affected by multi-drug resistance efflux pumps in either Enterobacteriaceae, or in non-fermenters such as P. aeruginosa or A. baumannii. In P. aeruginosa, the potency of QPX7728 was further enhanced when the outer membrane is permeabilized. The potency of QPX7728 in P. aeruginosa is not affected by inactivation of the carbapenem porin OprD. While changes in OmpK36 (but not OmpK35) reduced the potency of QPX7728 (8-16-fold), QPX7728 (4 μg/ml) nevertheless completely reversed KPC-mediated meropenem resistance in strains with porin mutations, consistent with a lesser effect of these mutations on the potency of QPX7728 compared to other agents. The ultra-broad-spectrum beta-lactamase inhibition profile combined with enhancement of the activity of multiple beta-lactam antibiotics with varying sensitivity to the intrinsic resistance mechanisms of efflux and permeability indicate QPX7728 is a useful inhibitor for use with multiple beta-lactam antibiotics.

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.

The human diseases caused by the fungal pathogens Cryptococcus neoformans and C. gattii are associated with high indices of mortality, and toxic and/or cost-prohibitive therapeutic protocols. The need for affordable antifungals to combat cryptococcal disease is unquestionable. Previous studies suggested benzimidazoles as promising anti-cryptococcal agents combining low cost and high antifungal efficacy, but their therapeutic potential has not been demonstrated so far. In this study, we investigated the antifungal potential of fenbendazole, the most effective anti-cryptococcal benzimidazole. Fenbendazole was inhibitory against 17 different isolates of C. neoformans and C. gattii at a low concentration. The mechanism of anti-cryptococcal activity of fenbendazole involved microtubule disorganization, as previously described for human parasites. In combination with fenbendazole, the concentrations of the standard antifungal amphotericin B required to control cryptococcal growth were lower than those required when this antifungal was used alone. Fenbendazole was not toxic to mammalian cells. During macrophage infection, the anti-cryptococcal effects of fenbendazole included inhibition of intracellular proliferation rates and reduced phagocytic escape through vomocytosis. Fenbendazole deeply affected the cryptococcal capsule. In a mice model of cryptococcosis, the efficacy of fenbendazole to control animal mortality was similar to that observed for amphotericin B. These results indicate that fenbendazole is a promising candidate for the future development of an efficient and affordable therapeutic tool to combat cryptococcosis.

Durlobactam (DUR, also known as ETX2514) is a novel β-lactamase inhibitor with broad activity against Ambler class A, C, and D β-lactamases. Addition of DUR to sulbactam (SUL) in vitro restores SUL activity against clinical isolates of Acinetobacter baumannii. The safety and pharmacokinetics (PK) of DUR alone and with SUL and/or imipenem/cilastatin (IMI/CIL) were evaluated in healthy subjects. This was a randomized, placebo-controlled study. In Part A, subjects including an elderly cohort (DUR 1 g) received single ascending doses of DUR 0.25-8 g. In Part B, multiple ascending dose of DUR 0.25-2 g were administered every 6 hours (q6h) for 29 doses. In Parts C and D, the drug-drug interaction (DDI) potential, including safety, of DUR (1 g) with SUL (1 g) and/or IMI/CIL (0.5/0.5 g) was investigated after single and multiple doses. Plasma and urine concentrations of DUR, SUL, and IMI/CIL were determined. Among 124 subjects, DUR was generally safe and well tolerated either alone or in combination with SUL and/or IMI/CIL. After single and multiple doses, DUR demonstrated linear dose proportional exposure across the studied dose ranges. Renal excretion was a predominant clearance mechanism. No drug:drug interaction potential was identified between DUR and SUL and/or IMI/CIL. SUL-DUR, 1 g (of each component) administered q6h with a 3 hour IV infusion, is under development for the treatment of serious infections due to A. baumannii.

We report the first clinical Escherichia. coli strain EC3000 with concomitant chromosomal colistin and carbapenem resistance. A novel in-frame deletion, 6-11(RPISLR), in pmrB contributing to colistin resistance was verified using recombinant DNA techniques. Although decreased fitness compared to the wild-type (WT) strain or EC3000 revertant (chromosomal replacement of WT pmrB in EC3000), a portion of serially passaged EC3000 strains preserving colistin resistance without selective pressure raises the concern for further spread.

Dihydroartemisinin-piperaquine has shown excellent efficacy and tolerability in malaria treatment. However, concerns have been raised of potentially harmful cardiotoxic effects associated with piperaquine. The population pharmacokinetics and cardiac effects of piperaquine were evaluated in 1,000 patients, mostly children enrolled in a multicentre trial from 10 sites in Africa. A linear relationship described the QTc-prolonging effect of piperaquine, estimating a 5.90ms mean QTc-prolongation per 100ng/mL increase in piperaquine concentration. The effect of piperaquine on absolute QTc-interval estimated a mean maximum QTc-interval of 456ms (EC₅₀=209ng/mL). Simulations from the pharmacokinetic-pharmacodynamic models predicted 1.98-2.46% risk of having QTc-prolongation > 60ms in all treatment settings. Although piperaquine administration resulted in QTc-prolongation, no cardiovascular adverse events were found in these patients. Thus, the use of dihydroartemisinin-piperaquine should not be limited by this concern.

Aspergillus niger, the third species responsible for invasive aspergillosis has been considered as a homogeneous species until DNA-based identification uncovered many cryptic species. These species have been recently reclassified into the Aspergillus section Nigri. However little is yet known among the section Nigri about the species distribution and the antifungal susceptibility pattern of each cryptic species. A total of 112 clinical isolates collected from 5 teaching hospitals in France and phenotypically identified as A. niger were analyzed. Identification to the species level was carried out by nucleotide sequence analysis. The Minimum Inhibitory Concentrations (MICs) of itraconazole, voriconazole, posaconazole, isavuconazole and amphotericin B were determined by both the EUCAST and gradient concentration strips methods. Aspergillus tubingensis (n=51, 45.5%) and A. welwitschiae (n=50, 44.6%) were the most common species while A. niger accounted for only 6.3% (n=7). The MICs of azoles drugs were higher for A. tubingensis than for A. welwitschiae. The MIC of amphotericin B was 2 mg/L or less for all isolates. Importantly, MICs determined by EUCAST showed no correlation with those determined by gradient concentration strips methods, these latter being lower than the former (Spearman's rank correlation tests ranging - depending on the antifungal agent - from 0.01 to 0.25; p>0.4). In conclusion, A. niger should be considered as a minority species in the section Nigri. The differences in MICs between species for different azoles underline the importance of accurate identification. Significant divergences in the determination of MIC between EUCAST and gradient concentration strips methods require further investigation.

Anidulafungin and micafungin were quantified in cerebrospinal fluid (CSF) of critically ill adults and in cerebral cortex of deceased patients. In CSF, anidulafungin levels (<0.01-0.66 μg/ml) and micafungin levels (<0.01-0.16 μg/ml) were lower than the simultaneous plasma concentrations (0.77-5.07 μg/ml and 1.21-8.70 μg/ml, respectively). In cerebral cortex, anidulafungin and micafungin levels were 0.21-2.34 μg/g and 0.18-2.88 μg/g, respectively. Thus, MIC values of several pathogenic Candida strains exceed concentrations in CSF and in brain.

Treatment of exacerbations of chronic Pseudomonas aeruginosa infections in patients with cystic fibrosis (CF) is highly challenging due to hypermutability, biofilm formation and an increased risk of resistance emergence. We evaluated the impact of ciprofloxacin and meropenem as monotherapy and in combination in the dynamic in vitro CDC biofilm reactor (CBR). Two hypermutable P. aeruginosa strains, PAOmutS (MIC_{ciprofloxacin} 0.25 mg/L, MIC_meropenem 2 mg/L) and CW44 (MIC_{ciprofloxacin} 0.5 mg/L, MIC_meropenem 4 mg/L), were investigated for 120h. Concentration-time profiles achievable in epithelial lining fluid (ELF) following FDA-approved doses were simulated in the CBR. Treatments were ciprofloxacin 0.4g every 8h as 1h-infusions (80% ELF penetration), meropenem 6 g/day as continuous infusion (CI; 30% and 60% ELF penetration) and their combinations. Counts of total and less-susceptible planktonic and biofilm bacteria and MICs were determined. Antibiotic concentrations were quantified by UHPLC-PDA. For both strains, all monotherapies failed with substantial regrowth and resistance of planktonic (≥8log₁₀ CFU/mL) and biofilm (>8log₁₀ CFU/cm²) bacteria at 120h (MIC_{ciprofloxacin} up to 8 mg/L, MIC_meropenem up to 64 mg/L). Both combination treatments demonstrated synergistic bacterial killing of planktonic and biofilm bacteria of both strains from ~48h onwards and suppressed regrowth to ≤4log₁₀ CFU/mL and ≤6log₁₀ CFU/cm² at 120h. Overall, both combination treatments suppressed amplification of resistance of planktonic bacteria for both strains, and biofilm bacteria for CW44. The combination with meropenem at 60% ELF penetration also suppressed amplification of resistance of biofilm bacteria for PAOmutS. Thus, combination treatment demonstrated synergistic bacterial killing and resistance suppression against difficult-to-treat hypermutable P. aeruginosa strains.

Parenting styles run the gamut and so do the features in parental control and monitoring utilities. We've tested the top hardware- and software-based services to help you choose the right one for your family.

Given that GoDaddy's GoCentral Online Store is an add-on service to its web hosting product, you'll find its features a little more limited than much of the competition. But if you're a GoDaddy customer, then it's a great way to start quickly.

Jose, an Argentinian worker serving in Southeast Asia, tells of how he entered overseas service and what he has seen God do through his not-so-typical ministry.

Jose, an Argentinian worker serving in Southeast Asia, tells of how he entered overseas service and what he has seen God do through his not-so-typical ministry.