Efficient luminescent solar concentrators based on self-absorption free, Tm2+ doped halides

The optical and luminescence properties of CaI2 and NaCl doped with divalent thulium are reported for solar energy applications. These halides strongly absorb solar light from the UV up to 900 nm due to the intense Tm2+ 4f13→4f125d1 electronic transitions. Absorption is followed by emission of 1140 nm light due to the 2F5/2→2F7/2 transition of the 4f13 configuration that can be efficiently converted to electric power by thin film CuInSe2 (CIS) solar cells. Because of a negligible spectral overlap between absorption and emission spectra, a luminescent solar concentrator (LSC) based on these black luminescent materials would not suffer from self-absorption losses. The Tm2+ doped halides may therefore lead to efficient semi-transparent power generating windows that absorb solar light over the whole visible spectrum. It will be shown that the power efficiency of the Tm2+ based LSCs can be up to four times higher compared to LSCs based on organic dyes or quantum dots.

The elusive S2 state, the S1/S2 splitting, and the excimer states of the benzene dimer

We observe the weak S 0 → S 2 transitions of the T-shaped benzene dimers (Bz)2 and (Bz-d 6)2 about 250 cm−1 and 220 cm−1 above their respective S 0 → S 1 electronic origins using two-color resonant two-photon ionization spectroscopy. Spin-component scaled (SCS) second-order approximate coupled-cluster (CC2) calculations predict that for the tipped T-shaped geometry, the S 0 → S 2 electronic oscillator strength f el (S 2) is ∼10 times smaller than f el (S 1) and the S 2 state lies ∼240 cm−1 above S 1, in excellent agreement with experiment. The S 0 → S 1 (ππ ∗) transition is mainly localized on the “stem” benzene, with a minor stem → cap charge-transfer contribution; the S 0 → S 2 transition is mainly localized on the “cap” benzene. The orbitals, electronic oscillator strengths f el (S 1) and f el (S 2), and transition frequencies depend strongly on the tipping angle ω between the two Bz moieties. The SCS-CC2 calculated S 1 and S 2 excitation energies at different T-shaped, stacked-parallel and parallel-displaced stationary points of the (Bz)2 ground-state surface allow to construct approximate S 1 and S 2 potential energy surfaces and reveal their relation to the “excimer” states at the stacked-parallel geometry. The f el (S 1) and f el (S 2) transition dipole moments at the C 2v -symmetric T-shape, parallel-displaced and stacked-parallel geometries are either zero or ∼10 times smaller than at the tipped T-shaped geometry. This unusual property of the S 0 → S 1 and S 0 → S 2 transition-dipole moment surfaces of (Bz)2 restricts its observation by electronic spectroscopy to the tipped and tilted T-shaped geometries; the other ground-state geometries are impossible or extremely difficult to observe. The S 0 → S 1/S 2 spectra of (Bz)2 are compared to those of imidazole ⋅ (Bz)2, which has a rigid triangular structure with a tilted (Bz)2 subunit. The S 0 → S 1/ S 2 transitions of imidazole-(benzene)2 lie at similar energies as those of (Bz)2, confirming our assignment of the (Bz)2 S 0 → S 2 transition.

Spatial genomic heterogeneity within localized, multifocal prostate cancer

Herein we provide a detailed molecular analysis of the spatial heterogeneity of clinically localized, multifocal prostate cancer to delineate new oncogenes or tumor suppressors. We initially determined the copy number aberration (CNA) profiles of 74 patients with index tumors of Gleason score 7. Of these, 5 patients were subjected to whole-genome sequencing using DNA quantities achievable in diagnostic biopsies, with detailed spatial sampling of 23 distinct tumor regions to assess intraprostatic heterogeneity in focal genomics. Multifocal tumors are highly heterogeneous for single-nucleotide variants (SNVs), CNAs and genomic rearrangements. We identified and validated a new recurrent amplification of MYCL, which is associated with TP53 deletion and unique profiles of DNA damage and transcriptional dysregulation. Moreover, we demonstrate divergent tumor evolution in multifocal cancer and, in some cases, tumors of independent clonal origin. These data represent the first systematic relation of intraprostatic genomic heterogeneity to predicted clinical outcome and inform the development of novel biomarkers that reflect individual prognosis.

Seven years of annual pollen influx at the forest limit in the Swiss Alps studied by pollen traps: relations to vegetation and climate

Annual pollen influx has been monitored in short transects across the altitudinal tree limit in four areas of the Swiss Alps with the use of modified Tauber traps placed at the ground surface. The study areas are Grindelwald (8 traps), Aletsch (8 traps), Simplon (5 traps), and Zermatt (5 traps). The vegetation around the traps is described. The results obtained are: (1) Peak years of pollen influx (one or two in seven years) follow years of high average air temperatures during June–November of the previous year for Larix and Picea, and less clearly for Pinus non-cembra, but not at all for Pinus cembra and Alnus viridis. (2) At the upper forest limit, the regional pollen influx of trees (trees absent within 100 m of the pollen trap) relates well to the average basal area of the same taxon within 10–15 km of the study areas for Pinus cembra, Larix, and Betula, but not for Picea, Pinus non-cembra, and Alnus viridis. (3) The example of Zermatt shows that pollen influx characterises the upper forest limit, if the latter is more or less intact. (4) Presence/absence of Picea, Pinus cembra, Larix, Pinus non-cembra, and Alnus viridis trees within 50–100 m of the traps is apparent in the pollen influx in peak years of pollen influx but not in other years, suggesting that forest-limit trees produce significant amounts of pollen only in some years. (5) Pollen influx averaged over the study period correlates well with the abundance of plants around the pollen traps for conifer trees (but not deciduous trees), Calluna, Gramineae, and Cyperaceae, and less clearly so Compositae Subfam. Cichorioideae and Potentilla-type. (6) Influx of extra-regional pollen derived from south of the Alps is highest in Simplon, which is open to southerly winds, slightly lower in Aletsch lying just north of Simplon, and lowest in Zermatt sheltered from the south by high mountains and Grindelwald lying north of the central Alps.

Palynostratigraphy of the last centuries in Switzerland based on 23 lake and mire deposits: chronostratigraphic pollen markers, regional patterns, and local histories

A total of 23 pollen diagrams [stored in the Alpine Palynological Data-Base (ALPADABA), Geobotanical Institute, Bern] cover the last 100 to over 1000 years. The sites include 15 lakes, seven mires, and one soil profile distributed in the Jura Mts (three sites), Swiss Plateau (two sites), northern Pre-Alps and Alps (six sites), central Alps (five sites), southern Alps (three sites), and southern Pre-Alps (four sites) in the western and southern part of Switzerland or just outside the national borders. The pollen diagrams have both a high taxonomic resolution and a high temporal resolution, with sampling distances of 0.5–3 cm, equivalent to 1 to 11 years for the last 100 years and 8 to 130 years for earlier periods. The chronology is based on absolute dating (14 sites: 210Pb 11 sites; 14C six sites; varve counting two sites) or on biostratigraphic correlation among pollen diagrams. The latter relies mainly on trends in Cannabis sativa, Ambrosia, Mercurialis annua, and Ostrya-type pollen. Individual pollen stratigraphies are discussed and sites are compared within each region. The principle of designating local, extra-local, and regional pollen signals and vegetation is exemplified by two pairs of sites lying close together. Trends in biostratigraphies shared by a major part of the pollen diagrams allow the following generalisations. Forest declined in phases since medieval times up to the late 19th century. Abies and Fagus declined consistently, whereas the behaviour of short-lived trees and trees of moist habitats differed among sites (Alnus glutinosa-type, Alnus viridis, Betula, Corylus avellana). In the present century, however, Picea and Pinus increased, followed by Fraxinus excelsior in the second half of this century. Grassland (traced by Gramineae and Plantago lanceolata-type pollen) increased, replacing much of the forest, and declined again in the second half of this century. Nitrate enrichment of the vegetation (traced by Urtica) took place in the first half of this century. These trends reflect the intensification of forest use and the expansion of grassland from medieval times up to the end of the last century, whereas subsequently parts of the grassland became used more intensively and the marginal parts were abandoned for forest regrowth. In most pollen diagrams human impact is the dominant factor in explaining inferred changes in vegetation, but climatic change plays a role at three sites.

Sedimentological and biostratigraphical analyses of short sediment cores from Hagelseewli (2339 m a.s.l.) in the Swiss Alps

Several short sediment cores of between 35 and 40 cm from Hagelseewli, a small, remote lake in the Swiss Alps at an elevation of 2339 m a.s.l. were correlated according to their organic matter content. The sediments are characterized by organic silts and show in their uppermost part a surprisingly high amount of organic matter (30-35%). Synchronous changes, occurring in pollen from snow-bed vegetation, the alga Pediastrum, chironomids, and grain-size composition, point to a climatic change interpreted as cooler or shorter summers that led to prolonged ice-cover on the lake. According to palynological results the sediments date back to at least the early 15th century A.D., with the cooling phase encompassing the period between late 16th and the mid-19th century thus coinciding with the Little Ice Age. Low concentrations of both chironomid head capsules and cladoceran remains in combination with results from fossil pigment analyses point to longer periods of bottom-water anoxia as a result of long-lasting ice-cover that prevented mixing of the water column. According to our results aquatic biota in Hagelseewli are mainly indirectly influenced by climate change. The duration of ice-cover on the lake controls the mixing of the water column as well as light-availability for phytoplankton blooms.

European S1 guideline for the treatment of hidradenitis suppurativa/acne inversa

Hidradenitis suppurativa/acne inversa (HS) is a chronic, inflammatory, recurrent, debilitating skin disease of the hair follicle that usually presents after puberty with painful, deep-seated, inflamed lesions in the apocrine gland-bearing areas of the body, most commonly the axillae, inguinal and anogenital regions. A mean disease incidence of 6.0 per 100,000 person-years and an average prevalence of 1% has been reported in Europe. HS has the highest impact on patients' quality of life among all assessed dermatological diseases. HS is associated with a variety of concomitant and secondary diseases, such as obesity, metabolic syndrome, inflammatory bowel disease, e.g. Crohn's disease, spondyloarthropathy, follicular occlusion syndrome and other hyperergic diseases. The central pathogenic event in HS is believed to be the occlusion of the upper part of the hair follicle leading to a perifollicular lympho-histiocytic inflammation. A highly significant association between the prevalence of HS and current smoking (Odds ratio 12.55) and overweight (Odds ratio 1.1 for each body mass index unit) has been documented. The European S1 HS guideline suggests that the disease should be treated based on its individual subjective impact and objective severity. Locally recurring lesions can be treated by classical surgery or LASER techniques, whereas medical treatment either as monotherapy or in combination with radical surgery is more appropriate for widely spread lesions. Medical therapy may include antibiotics (clindamycin plus rifampicine, tetracyclines), acitretin and biologics (adalimumab, infliximab). A Hurley severity grade-relevant treatment of HS is recommended by the expert group following a treatment algorithm. Adjuvant measurements, such as pain management, treatment of superinfections, weight loss and tobacco abstinence have to be considered.

Clinical Perspectives from Randomized Phase 3 Trials on Prostate Cancer: An Analysis of the ClinicalTrials.gov Database

AbstractBackground It is not easy to overview pending phase 3 trials on prostate cancer (PCa), and awareness of these trials would benefit clinicians. Objective To identify all phase 3 trials on {PCa} registered in the ClinicalTrials.gov database with pending results. Design and setting On September 29, 2014, a database was established from the records for 175 538 clinical trials registered on ClinicalTrials.gov. A search of this database for the substring “prostat” identified 2951 prostate trials. Phase 3 trials accounted for 441 studies, of which 333 concerned only PCa. We selected only ongoing or completed trials with pending results, that is, for which the primary endpoint had not been published in a peer-reviewed medical journal. Results and limitations We identified 123 phase 3 trials with pending results. Trials were conducted predominantly in North America (n = 63; 51) and Europe (n = 47; 38). The majority were on nonmetastatic disease (n = 82; 67), with 37 (30) on metastatic disease and four trials (3) including both. In terms of intervention, systemic treatment was most commonly tested (n = 71; 58), followed by local treatment 34 (28), and both systemic and local treatment (n = 11; 9), with seven (6) trials not classifiable. The 71 trials on systemic treatment included androgen deprivation therapy (n = 34; 48), chemotherapy (n = 15; 21), immunotherapy (n = 9; 13), other systemic drugs (n = 9; 13), radiopharmaceuticals (n = 2; 3), and combinations (n = 2; 3). Local treatments tested included radiation therapy (n = 27; 79), surgery (n = 5; 15), and both (n = 2; 2). A limitation is that not every clinical trial is registered on ClinicalTrials.gov. Conclusion There are many {PCa} phase 3 trials with pending results, most of which address questions regarding systemic treatments for both nonmetastatic and metastatic disease. Radiation therapy and androgen deprivation therapy are the interventions most commonly tested for local and systemic treatment, respectively. Patient summary This report describes all phase 3 trials on prostate cancer registered in the ClinicalTrials.gov database with pending results. Most of these trials address questions regarding systemic treatments for both nonmetastatic and metastatic disease. Radiation therapy and androgen deprivation therapy are the interventions most commonly tested for local and systemic treatment, respectively.

Diagnostic and Prognostic Impact of pc-ASPECTS Applied to Perfusion CT in the Basilar Artery International Cooperation Study

BACKGROUND AND PURPOSE The posterior circulation Acute Stroke Prognosis Early CT Score (pc-APECTS) applied to CT angiography source images (CTA-SI) predicts the functional outcome of patients in the Basilar Artery International Cooperation Study (BASICS). We assessed the diagnostic and prognostic impact of pc-ASPECTS applied to perfusion CT (CTP) in the BASICS registry population. METHODS We applied pc-ASPECTS to CTA-SI and cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) parameter maps of BASICS patients with CTA and CTP studies performed. Hypoattenuation on CTA-SI, relative reduction in CBV or CBF, or relative increase in MTT were rated as abnormal. RESULTS CTA and CTP were available in 27/592 BASICS patients (4.6%). The proportion of patients with any perfusion abnormality was highest for MTT (93%; 95% confidence interval [CI], 76%-99%), compared with 78% (58%-91%) for CTA-SI and CBF, and 46% (27%-67%) for CBV (P < .001). All 3 patients with a CBV pc-ASPECTS < 8 compared to 6/23 patients with a CBV pc-ASPECTS ≥ 8 had died at 1 month (RR 3.8; 95% CI, 1.9-7.6). CONCLUSION CTP was performed in a minority of the BASICS registry population. Perfusion disturbances in the posterior circulation were most pronounced on MTT parameter maps. CBV pc-ASPECTS < 8 may indicate patients with high case fatality.

Changes in chlamydia control activities in Europe between 2007 and 2012: a cross-national survey.

BACKGROUND In 2012, the levels of chlamydia control activities including primary prevention, effective case management with partner management and surveillance were assessed in 2012 across countries in the European Union and European Economic Area (EU/EEA), on initiative of the European Centre for Disease Control (ECDC) survey, and the findings were compared with those from a similar survey in 2007. METHODS Experts in the 30 EU/EEA countries were invited to respond to an online questionnaire; 28 countries responded, of which 25 participated in both the 2007 and 2012 surveys. Analyses focused on 13 indicators of chlamydia prevention and control activities; countries were assigned to one of five categories of chlamydia control. RESULTS In 2012, more countries than in 2007 reported availability of national chlamydia case management guidelines (80% vs. 68%), opportunistic chlamydia testing (68% vs. 44%) and consistent use of nucleic acid amplification tests (64% vs. 36%). The number of countries reporting having a national sexually transmitted infection control strategy or a surveillance system for chlamydia did not change notably. In 2012, most countries (18/25, 72%) had implemented primary prevention activities and case management guidelines addressing partner management, compared with 44% (11/25) of countries in 2007. CONCLUSION Overall, chlamydia control activities in EU/EEA countries strengthened between 2007 and 2012. Several countries still need to develop essential chlamydia control activities, whereas others may strengthen implementation and monitoring of existing activities.

Human graft-derived mesenchymal stromal cells potently suppress alloreactive T-cell responses

After organ transplantation, recipient T cells contribute to graft rejection. Mesenchymal stromal cells from the bone marrow (BM-MSCs) are known to suppress allogeneic T-cell responses, suggesting a possible clinical application of MSCs in organ transplantation. Human liver grafts harbor resident populations of MSCs (L-MSCs). We aimed to determine the immunosuppressive effects of these graft-derived MSCs on allogeneic T-cell responses and to compare these with the effects of BM-MSCs. BM-MSCs were harvested from aspirates and L-MSCs from liver graft perfusates. We cultured them for 21 days and compared their suppressive effects with the effects of BM-MSCs on allogeneic T-cell responses. Proliferation, cytotoxic degranulation, and interferon-gamma production of alloreactive T cells were more potently suppressed by L-MSCs than BM-MSCs. Suppression was mediated by both cell-cell contact and secreted factors. In addition, L-MSCs showed ex vivo a higher expression of PD-L1 than BM-MSCs, which was associated with inhibition of T-cell proliferation and cytotoxic degranulation in vitro. Blocking PD-L1 partly abrogated the inhibition of cytotoxic degranulation by L-MSCs. In addition, blocking indoleamine 2,3-dioxygenase partly abrogated the inhibitive effects of L-MSCs, but not BM-MSCs, on T-cell proliferation. In conclusion, liver graft-derived MSC suppression of allogeneic T-cell responses is stronger than BM-MSCs, which may be related to in situ priming and mobilization from the graft. These graft-derived MSCs may therefore be relevant in transplantation by promoting allohyporesponsiveness.

Towards mapping the late Quaternary vegetation change of Europe

The number of well-dated pollen diagrams in Europe has increased considerably over the last 30 years and many of them have been submitted to the European Pollen Database (EPD). This allows for the construction of increasingly precise maps of Holocene vegetation change across the continent. Chronological information in the EPD has been expressed in uncalibrated radiocarbon years, and most chronologies to date are based on this time scale. Here we present new chronologies for most of the datasets stored in the EPD based on calibrated radiocarbon years. Age information associated with pollen diagrams is often derived from the pollen stratigraphy itself or from other sedimentological information. We reviewed these chronological tie points and assigned uncertainties to them. The steps taken to generate the new chronologies are described and the rationale for a new classification system for age uncertainties is introduced. The resulting chronologies are fit for most continental-scale questions. They may not provide the best age model for particular sites, but may be viewed as general purpose chronologies. Taxonomic particularities of the data stored in the EPD are explained. An example is given of how the database can be queried to select samples with appropriate age control as well as the suitable taxonomic level to answer a specific research question.

Phenotype and genotype in 103 patients with tricho-rhino-phalangeal syndrome.

Tricho-rhino-phalangeal syndrome (TRPS) is characterized by craniofacial and skeletal abnormalities, and subdivided in TRPS I, caused by mutations in TRPS1, and TRPS II, caused by a contiguous gene deletion affecting (amongst others) TRPS1 and EXT1. We performed a collaborative international study to delineate phenotype, natural history, variability, and genotype-phenotype correlations in more detail. We gathered information on 103 cytogenetically or molecularly confirmed affected individuals. TRPS I was present in 85 individuals (22 missense mutations, 62 other mutations), TRPS II in 14, and in 5 it remained uncertain whether TRPS1 was partially or completely deleted. Main features defining the facial phenotype include fine and sparse hair, thick and broad eyebrows, especially the medial portion, a broad nasal ridge and tip, underdeveloped nasal alae, and a broad columella. The facial manifestations in patients with TRPS I and TRPS II do not show a significant difference. In the limbs the main findings are short hands and feet, hypermobility, and a tendency for isolated metacarpals and metatarsals to be shortened. Nails of fingers and toes are typically thin and dystrophic. The radiological hallmark are the cone-shaped epiphyses and in TRPS II multiple exostoses. Osteopenia is common in both, as is reduced linear growth, both prenatally and postnatally. Variability for all findings, also within a single family, can be marked. Morbidity mostly concerns joint problems, manifesting in increased or decreased mobility, pain and in a minority an increased fracture rate. The hips can be markedly affected at a (very) young age. Intellectual disability is uncommon in TRPS I and, if present, usually mild. In TRPS II intellectual disability is present in most but not all, and again typically mild to moderate in severity. Missense mutations are located exclusively in exon 6 and 7 of TRPS1. Other mutations are located anywhere in exons 4-7. Whole gene deletions are common but have variable breakpoints. Most of the phenotype in patients with TRPS II is explained by the deletion of TRPS1 and EXT1, but haploinsufficiency of RAD21 is also likely to contribute. Genotype-phenotype studies showed that mutations located in exon 6 may have somewhat more pronounced facial characteristics and more marked shortening of hands and feet compared to mutations located elsewhere in TRPS1, but numbers are too small to allow firm conclusions.

A legacy of human-induced ecosystem changes: spatial processes drive the taxonomic and functional diversities of testate amoebae in Sphagnum peatlands of the Galápagos

Aim Our aims were to compare the composition of testate amoeba (TA) communities from Santa Cruz Island, Galápagos Archipelago, which are likely in existence only as a result of anthropogenic habitat transformation, with similar naturally occurring communities from northern and southern continental peatlands. Additionally, we aimed at assessing the importance of niche-based and dispersal-based processes in determining community composition and taxonomic and functional diversity. Location The humid highlands of the central island of Santa Cruz, Galápagos Archipelago. Methods We survey the alpha, beta and gamma taxonomic and functional diversities of TA, and the changes in functional traits along a gradient of wet to dry habitats. We compare the TA community composition, abundance and frequency recorded in the insular peatlands with that recorded in continental peatlands of Northern and Southern Hemispheres. We use generalized linear models to determine how environmental conditions influence taxonomic and functional diversity as well as the mean values of functional traits within communities. We finally apply variance partitioning to assess the relative importance of niche- and dispersal-based processes in determining community composition. Results TA communities in Santa Cruz Island were different from their Northern Hemisphere and South American counterparts with most genera considered as characteristic for Northern Hemisphere and South American Sphagnum peatlands missing or very rare in the Galápagos. Functional traits were most correlated with elevation and site topography and alpha functional diversity to the type of material sampled and site topography. Community composition was more strongly correlated with spatial variables than with environmental ones. Main conclusions TA communities of the Sphagnum peatlands of Santa Cruz Island and the mechanisms shaping these communities contrast with Northern Hemisphere and South American peatlands. Soil moisture was not a strong predictor of community composition most likely because rainfall and clouds provide sufficient moisture. Dispersal limitation was more important than environmental filtering because of the isolation of the insular peatlands from continental ones and the young ecological history of these ecosystems.

Early growth characteristics and the risk of reduced lung function and asthma: A meta-analysis of 25,000 children

BACKGROUND Children born preterm or with a small size for gestational age are at increased risk for childhood asthma. OBJECTIVE We sought to assess the hypothesis that these associations are explained by reduced airway patency. METHODS We used individual participant data of 24,938 children from 24 birth cohorts to examine and meta-analyze the associations of gestational age, size for gestational age, and infant weight gain with childhood lung function and asthma (age range, 3.9-19.1 years). Second, we explored whether these lung function outcomes mediated the associations of early growth characteristics with childhood asthma. RESULTS Children born with a younger gestational age had a lower FEV1, FEV1/forced vital capacity (FVC) ratio, and forced expiratory volume after exhaling 75% of vital capacity (FEF75), whereas those born with a smaller size for gestational age at birth had a lower FEV1 but higher FEV1/FVC ratio (P < .05). Greater infant weight gain was associated with higher FEV1 but lower FEV1/FVC ratio and FEF75 in childhood (P < .05). All associations were present across the full range and independent of other early-life growth characteristics. Preterm birth, low birth weight, and greater infant weight gain were associated with an increased risk of childhood asthma (pooled odds ratio, 1.34 [95% CI, 1.15-1.57], 1.32 [95% CI, 1.07-1.62], and 1.27 [95% CI, 1.21-1.34], respectively). Mediation analyses suggested that FEV1, FEV1/FVC ratio, and FEF75 might explain 7% (95% CI, 2% to 10%) to 45% (95% CI, 15% to 81%) of the associations between early growth characteristics and asthma. CONCLUSIONS Younger gestational age, smaller size for gestational age, and greater infant weight gain were across the full ranges associated with childhood lung function. These associations explain the risk of childhood asthma to a substantial extent.