Histology Matters: Individualizing Treatment in Non-Small Cell Lung Cancer

This editorial discusses the role of histology in non-small cell lung cancer treatment

A picogram and nanometer scale photonic crystal opto-mechanical cavity

We describe the design, fabrication, and measurement of a cavity opto-mechanical system consisting of two nanobeams of silicon nitride in the near-field of each other, forming a so-called "zipper" cavity. A photonic crystal patterning is applied to the nanobeams to localize optical and mechanical energy to the same cubic-micron-scale volume. The picrogram-scale mass of the structure, along with the strong per-photon optical gradient force, results in a giant optical spring effect. In addition, a novel damping regime is explored in which the small heat capacity of the zipper cavity results in blue-detuned opto-mechanical damping.Comment: 15 pages, 4 figure

Influence of Thoracic Fluid Compartments on Pulmonary Congestion in Chronic Heart Failure

Introduction: Pulmonary congestion is a common finding of heart failure (HF), but it remains unclear how pulmonary and heart blood volumes (Vp and Vh, respectively) and extravascular lung water (EVLW) change in stable HF and affect lung function. Methods: Fourteen patients with HF (age 68 ± 11 y, LVEF 33 ± 8%) and 12 control subjects (age 65 ± 9 y) were recruited. A pulmonary function test, thoracic computerized tomographic (CT) scan, and contrast perfusion scan were performed. From the thoracic scan, a histogram of CT attenuation of lung tissue was generated and skew, kurtosis, and full-width half-max (FWHM) calculated as surrogates of EVLW. Blood volumes were calculated from the transit time of the contrast through the great vessels of the heart. Results: Patients with HF had greater Vp and Vh (Vp 0.55 ± 0.21 L vs 0.41 ± 0.13 L; Vh 0.53 ± 0.33 L vs 0.40 ± 0.15 L) and EVLW (skew 3.2 ± 0.5 vs 3.7 ± 0.7; kurtosis 19.4 ± 6.6 vs 25.9 ± 9.4; FWHM 73 ± 13 HU vs 59 ± 9 HU). Spirometric measures were decreased in HF (percentage of predicted: forced vital capacity 86 ± 17% vs 104 ± 9%; forced expiratory volume in 1 second 83 ± 20% vs 105 ± 11%; maximal mid-expiratory flow 82 ± 42% vs 115 ± 43%). Vp was associated with decreased expiratory flows, and EVLW was associated with decreased lung volumes. Conclusions: Congestion in stable patients with HF includes expanded Vp and Vh and increased EVLW associated with reductions in lung volumes and expiratory flows

Measuring Coverage in MNCH:A Validation Study Linking Population Survey Derived Coverage to Maternal, Newborn, and Child Health Care Records in Rural China

Accurate data on coverage of key maternal, newborn, and child health (MNCH) interventions are crucial for monitoring progress toward the Millennium Development Goals 4 and 5. Coverage estimates are primarily obtained from routine population surveys through self-reporting, the validity of which is not well understood. We aimed to examine the validity of the coverage of selected MNCH interventions in Gongcheng County, China.We conducted a validation study by comparing women's self-reported coverage of MNCH interventions relating to antenatal and postnatal care, mode of delivery, and child vaccinations in a community survey with their paper- and electronic-based health care records, treating the health care records as the reference standard. Of 936 women recruited, 914 (97.6%) completed the survey. Results show that self-reported coverage of these interventions had moderate to high sensitivity (0.57 [95% confidence interval (CI): 0.50-0.63] to 0.99 [95% CI: 0.98-1.00]) and low to high specificity (0 to 0.83 [95% CI: 0.80-0.86]). Despite varying overall validity, with the area under the receiver operating characteristic curve (AUC) ranging between 0.49 [95% CI: 0.39-0.57] and 0.90 [95% CI: 0.88-0.92], bias in the coverage estimates at the population level was small to moderate, with the test to actual positive (TAP) ratio ranging between 0.8 and 1.5 for 24 of the 28 indicators examined. Our ability to accurately estimate validity was affected by several caveats associated with the reference standard. Caution should be exercised when generalizing the results to other settings.The overall validity of self-reported coverage was moderate across selected MNCH indicators. However, at the population level, self-reported coverage appears to have small to moderate degree of bias. Accuracy of the coverage was particularly high for indicators with high recorded coverage or low recorded coverage but high specificity. The study provides insights into the accuracy of self-reports based on a population survey in low- and middle-income countries. Similar studies applying an improved reference standard are warranted in the future

The implications of the United Nations Paris Agreement on climate change for globally significant biodiversity areas

Climate change is already affecting species and their distributions. Distributional range changes have occurred and are projected to intensify for many widespread plants and animals, creating associated risks to many ecosystems. Here, we estimate the climate change-related risks to the species in globally significant biodiversity conservation areas over a range of climate scenarios, assessing their value as climate refugia. In particular, we quantify the aggregated benefit of countries’ emission reduction pledges (Intended Nationally Determined Contributions and Nationally Determined Contributions under the Paris Agreement), and also of further constraining global warming to 2 °C above pre-industrial levels, against an unmitigated scenario of 4.5 °C warming. We also quantify the contribution that can be made by using smart spatial conservation planning to facilitate some levels of autonomous (i.e. natural) adaptation to climate change by dispersal. We find that without mitigation, on average 33% of each conservation area can act as climate refugium (or 18% if species are unable to disperse), whereas if warming is constrained to 2 °C, the average area of climate refuges doubles to 67% of each conservation area (or, without dispersal, more than doubles to 56% of each area). If the country pledges are fulfilled, an intermediate estimate of 47–52% (or 31–38%, without dispersal) is obtained. We conclude that the Nationally Determined Contributions alone have important but limited benefits for biodiversity conservation, with larger benefits accruing if warming is constrained to 2 °C. Greater benefits would result if warming was constrained to well below 2 °C as set out in the Paris Agreement

Complete chloroplast genome sequence of Holoparasite Cistanche Deserticola (Orobanchaceae) reveals gene loss and horizontal gene transfer from Its host Haloxylon Ammodendron (Chenopodiaceae)

The central function of chloroplasts is to carry out photosynthesis, and its gene content and structure are highly conserved across land plants. Parasitic plants, which have reduced photosynthetic ability, suffer gene losses from the chloroplast (cp) genome accompanied by the relaxation of selective constraints. Compared with the rapid rise in the number of cp genome sequences of photosynthetic organisms, there are limited data sets from parasitic plants. The authors report the complete sequence of the cp genome of Cistanche deserticola, a holoparasitic desert species belonging to the family Orobanchaceae

A fresh look at the evolution and diversification of photochemical reaction centers

In this review, I reexamine the origin and diversification of photochemical reaction centers based on the known phylogenetic relations of the core subunits, and with the aid of sequence and structural alignments. I show, for example, that the protein folds at the C-terminus of the D1 and D2 subunits of Photosystem II, which are essential for the coordination of the water-oxidizing complex, were already in place in the most ancestral Type II reaction center subunit. I then evaluate the evolution of reaction centers in the context of the rise and expansion of the different groups of bacteria based on recent large-scale phylogenetic analyses. I find that the Heliobacteriaceae family of Firmicutes appears to be the earliest branching of the known groups of phototrophic bacteria; however, the origin of photochemical reaction centers and chlorophyll synthesis cannot be placed in this group. Moreover, it becomes evident that the Acidobacteria and the Proteobacteria shared a more recent common phototrophic ancestor, and this is also likely for the Chloroflexi and the Cyanobacteria. Finally, I argue that the discrepancies among the phylogenies of the reaction center proteins, chlorophyll synthesis enzymes, and the species tree of bacteria are best explained if both types of photochemical reaction centers evolved before the diversification of the known phyla of phototrophic bacteria. The primordial phototrophic ancestor must have had both Type I and Type II reaction centers

Cardiogenic Induction of Pluripotent Stem Cells Streamlined Through a Conserved SDF-1/VEGF/BMP2 Integrated Network

BACKGROUND: Pluripotent stem cells produce tissue-specific lineages through programmed acquisition of sequential gene expression patterns that function as a blueprint for organ formation. As embryonic stem cells respond concomitantly to diverse signaling pathways during differentiation, extraction of a pro-cardiogenic network would offer a roadmap to streamline cardiac progenitor output. METHODS AND RESULTS: To resolve gene ontology priorities within precursor transcriptomes, cardiogenic subpopulations were here generated according to either growth factor guidance or stage-specific biomarker sorting. Innate expression profiles were independently delineated through unbiased systems biology mapping, and cross-referenced to filter transcriptional noise unmasking a conserved progenitor motif (55 up- and 233 down-regulated genes). The streamlined pool of 288 genes organized into a core biological network that prioritized the "Cardiovascular Development" function. Recursive in silico deconvolution of the cardiogenic neighborhood and associated canonical signaling pathways identified a combination of integrated axes, CXCR4/SDF-1, Flk-1/VEGF and BMP2r/BMP2, predicted to synchronize cardiac specification. In vitro targeting of the resolved triad in embryoid bodies accelerated expression of Nkx2.5, Mef2C and cardiac-MHC, enhanced beating activity, and augmented cardiogenic yield. CONCLUSIONS: Transcriptome-wide dissection of a conserved progenitor profile thus revealed functional highways that coordinate cardiogenic maturation from a pluripotent ground state. Validating the bioinformatics algorithm established a strategy to rationally modulate cell fate, and optimize stem cell-derived cardiogenesis