Redetermination of (E)-N,N′-bis­(4-bromo­phen­yl)formamidine

In comprison with the previous structural study [Anulewicz et al. (1991 ▶). Pol. J. Chem. 65, 465–471], for which only the coordinates of all non-H atoms and of some H atoms were reported, the current redetermination of the title compound, C13H10Br2N2, additionally reports anisotropic displacement parameters for all non-H atoms and the coordinates of all H atoms, accompanied by higher accuracy of the geometric parameters. Two independent half-mol­ecules are present in the asymmetric unit, which are completed by a twofold rotation axis as symmetry element. In the crystal, inter­molecular N—H⋯N hydrogen bonds link the mol­ecules into dimers. Linear chains parallel to [102] are formed by inter­molecular Br⋯Br inter­actions of 3.4328 (7) Å between two Br atoms of adjacent mol­ecules. The dihedral angles between the benzene rings are 50.05 (15) and 75.61 (11)° in the two independent molecules. Owing to the twofold symmetry of the mol­ecules, H atoms attached to the N atoms are only half-occupied, leading to them being disordered over two positions of equal occupancy

Different carbon isotope fractionation patterns during the development of phototrophic freshwater and marine biofilms

Natural phototrophic biofilms are influenced by a broad array of abiotic and biotic factors and vary over temporal and spatial scales. Different developmental stages can be distinguished and growth rates will vary due to the thickening of the biofilm, which is expected to lead to a limitation of light or mass transport. This study shows that variation in CO<sub>2(aq)</sub> availability leads to a fractionation shift and thereby affects δ<sup>13</sup>C signatures during biofilm development. For phototrophic freshwater biofilms it was found that the δ<sup>13</sup>C value became less negative with the thickening of the biofilm, while the opposite trend was found in marine biofilms. Modeling and pH profiling indicated that the trend in the freshwater system was caused by an increase in CO<sub>2(aq)</sub> limitation resulting in an increase of HCO<sub>3</sub><sup>−</sup> as C-source. The opposite trend in the marine system could be explained by a higher heterotrophic biomass and activity causing a higher carbon recycling and thereby lower δ<sup>13</sup>C values. We conclude that δ<sup>13</sup>C was more related to the net areal photosynthesis rate and carbon recycling, rather than to the growth rate of the biofilms

Successful elimination of falciparum malaria following the introduction of community-based health workers in Eastern Myanmar: a retrospective analysis

Background: Myanmar has a large majority of all malaria in the Greater Mekong Subregion. In the past decade, substantial progress was made in malaria control. The residual burden of malaria is in remote areas where currently recommended malaria elimination approaches are generally not feasible. In such hard-to-reach communities in Mon state, East Myanmar, Medical Action Myanmar introduced community health workers (CHWs) to deliver early diagnosis and treatment for malaria. We conducted a retrospective analysis to assess the impact of this intervention. Methods and findings: This retrospective analysis involved data collected routinely from a CHW programme in Mon state conducted between 2011 and 2018. A network of 172 CHWs serving a population of 236,340 was deployed. These CHWs carried out 260,201 malaria rapid diagnostic tests (RDTs) to investigate patients with acute febrile illness. The median blood examination rate was 1.33%; interquartile range (IQR) (0.38 to 3.48%); 95% CI [1.28%, 1.36%] per month. The changes in malaria incidence and prevalence in patients presenting with fever were assessed using negative binomial regression mixed effects models fitted to the observed data. The incidence of Plasmodium falciparum malaria (including mixed infections) declined by 70%; 95% CI [65%, 75%]; p < 0.001 for each year of CHW operation. The incidence of P. vivax malaria declined by 56%; 95% CI [50%, 62%]; p < 0.001 per year. Malaria RDT positivity rates for P. falciparum and P. vivax declined by 69%; 95% CI [62%, 75%]; p < 0.001 and 53%; 95% CI [47%, 59%]; p < 0.001 per year, respectively. Between 2017 and 2018, only 1 imported P. falciparum case was detected in 54,961 RDTs. The main limitations of the study are use of retrospective data with possible unidentified confounders and uncharacterised population movement. Conclusions: The introduction of CHWs providing community-based malaria diagnosis and treatment and basic health care services in remote communities in Mon state was associated with a substantial reduction in malaria. Within 6 years, P. falciparum was eliminated and the incidence of P. vivax fell markedly

Dispersal Ability Predicts Spatial Genetic Structure in Native Mammals Persisting across an Urbanization Gradient

As the rate of urbanization continues to increase globally, a growing body of research is emerging that investigates how urbanization shapes the movement—and consequent gene flow—of species in cities. Of particular interest are native species that persist in cities, either as small relict populations or as larger populations of synanthropic species that thrive alongside humans in new urban environments. In this study, we used genomic sequence data (SNPs) and spatially explicit individual‐based analyses to directly compare the genetic structure and patterns of gene flow in two small mammals with different dispersal abilities that occupy the same urbanized landscape to evaluate how mobility impacts genetic connectivity. We collected 215 white‐footed mice (Peromyscus leucopus) and 380 big brown bats (Eptesicus fuscus) across an urban‐to‐rural gradient within the Providence, Rhode Island (U.S.A.) metropolitan area (population =1,600,000 people). We found that mice and bats exhibit clear differences in their spatial genetic structure that are consistent with their dispersal abilities, with urbanization having a stronger effect on Peromyscus mice. There were sharp breaks in the genetic structure of mice within the Providence urban core, as well as reduced rates of migration and an increase in inbreeding with more urbanization. In contrast, bats showed very weak genetic structuring across the entire study area, suggesting a near‐panmictic gene pool likely due to the ability to disperse by flight. Genetic diversity remained stable for both species across the study region. Mice also exhibited a stronger reduction in gene flow between island and mainland populations than bats. This study represents one of the first to directly compare multiple species within the same urban‐to‐rural landscape gradient, an important gap to fill for urban ecology and evolution. Moreover, here we document the impacts of dispersal capacity on connectivity for native species that have persisted as the urban landscape matrix expands

Curved Tails in Polymerization-Based Bacterial Motility

The curved actin ``comet-tail'' of the bacterium Listeria monocytogenes is a visually striking signature of actin polymerization-based motility. Similar actin tails are associated with Shigella flexneri, spotted-fever Rickettsiae, the Vaccinia virus, and vesicles and microspheres in related in vitro systems. We show that the torque required to produce the curvature in the tail can arise from randomly placed actin filaments pushing the bacterium or particle. We find that the curvature magnitude determines the number of actively pushing filaments, independent of viscosity and of the molecular details of force generation. The variation of the curvature with time can be used to infer the dynamics of actin filaments at the bacterial surface.Comment: 8 pages, 2 figures, Latex2

Sequential decoupling of negative-energy states in Douglas-Kroll-Hess theory

Here, we review the historical development, current status, and prospects of Douglas--Kroll--Hess theory as a quantum chemical relativistic electrons-only theory.Comment: 15 page

Changes in the serum proteome associated with the development of hepatocellular carcinoma in hepatitis C-related cirrhosis

Early diagnosis of hepatocellular carcinoma (HCC) is the key to the delivery of effective therapies. The conventional serological diagnostic test, estimation of serum alpha-fetoprotein (AFP) lacks both sensitivity and specificity as a screening tool and improved tests are needed to complement ultrasound scanning, the major modality for surveillance of groups at high risk of HCC. We have analysed the serum proteome of 182 patients with hepatitis C-induced liver cirrhosis (77 with HCC) by surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI). The patients were split into a training set (84 non-HCC, 60 HCC) and a ‘blind' test set (21 non-HCC, 17 HCC). Neural networks developed on the training set were able to classify the blind test set with 94% sensitivity (95% CI 73–99%) and 86% specificity (95% CI 65–95%). Two of the SELDI peaks (23/23.5 kDa) were elevated by an average of 50% in the serum of HCC patients (P<0.001) and were identified as κ and λ immunoglobulin light chains. This approach may permit identification of several individual proteins, which, in combination, may offer a novel way to diagnose HCC

Mass drug administration for the acceleration of malaria elimination in a region of Myanmar with artemisinin-resistant falciparum malaria: a cluster-randomised trial

Background: To contain multidrug-resistant Plasmodium falciparum, malaria elimination in the Greater Mekong subregion needs to be accelerated while current antimalarials remain effective. We evaluated the safety, effectiveness, and potential resistance selection of dihydroartemisinin–piperaquine mass drug administration (MDA) in a region with artemisinin resistance in Myanmar. Methods: We did a cluster-randomised controlled trial in rural community clusters in Kayin (Karen) state in southeast Myanmar. Malaria prevalence was assessed using ultrasensitive quantitative PCR (uPCR) in villages that were operationally suitable for MDA (villages with community willingness, no other malaria control campaigns, and a population of 50–1200). Villages were eligible to participate if the prevalence of malaria (all species) in adults was greater than 30% or P falciparum prevalence was greater than 10% (or both). Contiguous villages were combined into clusters. Eligible clusters were paired based on P falciparum prevalence (estimates within 10%) and proximity. Community health workers provided routine malaria case management and distributed long-lasting insecticidal bed-nets (LLINs) in all clusters. Randomisation of clusters (1:1) to the MDA intervention group or control group was by public coin-flip. Group allocations were not concealed. Three MDA rounds (3 days of supervised dihydroartemisinin–piperaquine [target total dose 7 mg/kg dihydroartemisinin and 55 mg/kg piperaquine] and single low-dose primaquine [target dose 0·25 mg base per kg]) were delivered to intervention clusters. Parasitaemia prevalence was assessed at 3, 5, 10, 15, 21, 27, and 33 months. The primary outcomes were P falciparum prevalence at months 3 and 10. All clusters were included in the primary analysis. Adverse events were monitored from the first MDA dose until 1 month after the final dose, or until resolution of any adverse event occurring during follow-up. This trial is registered with ClinicalTrials.gov, NCT01872702. Findings: Baseline uPCR malaria surveys were done in January, 2015, in 43 villages that were operationally suitable for MDA (2671 individuals). 18 villages met the eligibility criteria. Three villages in close proximity were combined into one cluster because a border between them could not be defined. This gave a total of 16 clusters in eight pairs. In the intervention clusters, MDA was delivered from March 4 to March 17, from March 30 to April 10, and from April 27 to May 10, 2015. The weighted mean absolute difference in P falciparum prevalence in the MDA group relative to the control group was −10·6% (95% CI −15·1 to −6·1; p=0·0008) at month 3 and −4·5% (−10·9 to 1·9; p=0·14) at month 10. At month 3, the weighted P falciparum prevalence was 1·4% (0·6 to 3·6; 12 of 747) in the MDA group and 10·6% (7·0 to 15·6; 56 of 485) in the control group. Corresponding prevalences at month 10 were 3·2% (1·5 to 6·8; 34 of 1013) and 5·8% (2·5 to 12·9; 33 of 515). Adverse events were reported for 151 (3·6%) of 4173 treated individuals. The most common adverse events were dizziness (n=109) and rash or itching (n=20). No treatment-related deaths occurred. Interpretation: In this low-transmission setting, the substantial reduction in P falciparum prevalence resulting from support of community case management was accelerated by MDA. In addition to supporting community health worker case management and LLIN distribution, malaria elimination programmes should consider using MDA to reduce P falciparum prevalence rapidly in foci of higher transmission. Funding: The Global Fund to Fight AIDS, Tuberculosis and Malaria

Preclinical and post-treatment changes in the HCC-associated serum proteome

SELDI-based proteomic profiling of body fluids is currently in widespread use for cancer biomarker discovery. We have successfully used this technology for the diagnosis of hepatocellular carcinoma (HCC) in hepatitis C patients and now report its application to serial serum samples from 37 hepatitis C patients before development of HCC, with HCC and following radiofrequency ablation of the tumour. As with alpha-fetoprotein, an accepted biomarker for HCC, we hypothesised that HCC-associated proteomic features would ‘return to normal' following successful treatment and the primary aim of our study was to test this hypothesis. Several SELDI peaks that changed significantly during HCC development were detected but they did not reverse following treatment. These data may be interpreted to suggest that the characteristic SELDI profile is not linearly related to tumour burden but may result from the progression of underlying liver disease or from the emergence of precancerous lesions. β2-Microglobulin, a protein previously reported to be markedly elevated in patients with HCV related HCC, was also the most significantly HCC associated proteomic feature (m/z 11720) in this study

Ultrafast structure and dynamics in ionic liquids: 2D-IR spectroscopy probes the molecular origin of viscosity

The viscosity of imidazolium ionic liquids increases dramatically when the strongest hydrogen bonding location is methylated. In this work, ultrafast two-dimensional vibrational spectroscopy of dilute thiocyanate ion ([SCN] -) in 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([C4C1im][NTf2]) and 1-butyl-2,3- dimethylimidazolium bis(trifluoromethylsulfonyl)imide ([C4C 1C12im][NTf2]) shows that the structural reorganization occurs on a 26 ± 3 ps time scale and on a 47 ± 15 ps time scale, respectively. The results suggest that the breakup of local ion-cages is the fundamental event that activates molecular diffusion and determines the viscosity of the fluids. © 2014 American Chemical Society