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Background. Up to a quarter of inpatients in high-income countries (HICs) self-report beta-lactam allergy (BLA), which if incorrect,increases the use of alternative antibiotics, worsening individual health outcomes and driving bacterial resistance. In HICs, up to 95% ofself-reported BLAs are incorrect. The epidemiology of BLA in low- and middle-income African countries is unknown.Objectives. To describe the epidemiology and de-labelling outcomes of self-reported BLA in hospitalised South African (SA) patients.Methods. Point-prevalence surveys were conducted at seven hospitals (adult, paediatric, government and privately funded, district andtertiary level) in Cape Town, SA, between April 2019 and June 2021. Ward prescription records and in-person interviews were conductedto identify and risk-stratify BLA patients using the validated PEN-FAST tool. De-labelling was attempted at the tertiary allergy clinic atGroote Schuur Hospital.Results. A total of 1 486 hospital inpatients were surveyed (1 166 adults and 320 children). Only 48 patients (3.2%) self-reported a BLA,with a higher rate in private than in government-funded hospitals (6.3% v. 2.8%; p=0.014). Using the PEN-FAST tool, only 10.4% (n=5/48)of self-reported BLA patients were classified as high risk for true penicillin hypersensitivity. Antibiotics were prescribed to 70.8% (n=34/48)of self-reported BLA patients, with 64.7% (n=22/34) receiving a beta-lactam. Despite three attempts to contact patients for de-labelling atthe allergy clinic, only 3/36 underwent in vivo testing, with no positive results, and 1 patient proceeded to a negative oral challenge.Conclusion. Unlike HICs, self-reported BLA is low among inpatients in SA. The majority of those who self-reported BLA were low risk fortype 1 hypersensitivity, but outpatient de-labelling efforts were largely unsuccessful.

Rising oceanic temperatures create more frequent coral bleaching events worldwide and as such there exists a need for rapid, non-destructive survey techniques to gather greater and higher definition information than that offered by traditional spectral based monitoring systems. Here, we examine thermally induced laboratory bleaching of Montipora capricornis and Montipora confusa samples, utilising hyperspectral data to gain an understanding of coral bleaching from a spectral standpoint. The data revealed several characteristic spectral peaks that can be used to make health determinations. The fluorescence peaks are attributed to fluorescent proteins (FPs) and Chlorophyll-a fluorescence. The reflectance peaks can be attributed to Chlorophyll absorption and accessory pigments such as Peridinin and Diadinoxanthin. Each characteristic spectral peak or ‘marker’ allows for observation of each aspect of coral health and hence, simultaneous monitoring of these markers using hyperspectral imaging techniques provides an opportunity to better understand the processes occurring during bleaching and the rates at which they occur relative to one another.

BACKGROUND: Recent national data suggests that less than 0.5% of NHS cataract patients undergo immediate sequential bilateral cataract surgery (ISBCS). Since ISBCS improves service efficiency, increasing its practice may help tackle the ever-growing burden of cataract in the UK, and reduce the COVID-19 cataract backlog. Surgeon attitudes are known to be a significant barrier to increasing the practice of ISBCS. However, little is known about patient perceptions of ISBCS. METHODS: Patients at cataract clinics across three NHS hospital sites were recruited to complete an investigator-led structured questionnaire. Open-ended and closed-ended questions were used to assess awareness of ISBCS, willingness to undergo ISBCS and attitudes towards ISBCS. RESULTS: Questionnaires were completed by 183 patients. Mean participant age was 70.5 (9.9) years and 58% were female. Forty-three percent were aware of ISBCS, chiefly via clinic staff. Just over a third would choose ISBCS if given the choice, and participants that perceived they were recommended ISBCS were more likely to opt for it. The most common motivator and barrier to uptake of ISBCS was convenience and the perceived risk of complications in both eyes respectively. Concerns related to the recovery period were common, including misunderstandings, such as the need to wear eye patches that obscure both eyes. CONCLUSIONS: Our study indicates that significantly more NHS patients would be willing to undergo ISBCS if given the choice. The reluctance of surgeons to recommend ISBCS and patient misunderstandings regarding the recovery period may be limiting its uptake.

Limb buds develop as bilateral outgrowths of the lateral plate mesoderm and are patterned along three axes. Current models of proximal to distal patterning of early amniote limb buds suggest that two signals, a distal organizing signal from the apical epithelial ridge (AER, Fgfs) and an opposing proximal (retinoic acid [RA]) act early on pattern this axis.Transcriptional analysis of stage 51 Xenopus laevis hindlimb buds sectioned along the proximal-distal axis showed that the distal region is distinct from the rest of the limb. Expression of capn8.3, a novel calpain, was located in cells immediately flanking the AER. The Wnt antagonist Dkk1 was AER-specific in Xenopus limbs. Two transcription factors, sall1 and zic5, were expressed in distal mesenchyme. Zic5 has no described association with limb development. We also describe expression of two proximal genes, gata5 and tnn, not previously associated with limb development. Differentially expressed genes were associated with Fgf, Wnt, and RA signaling as well as differential cell adhesion and proliferation.We identify new candidate genes for early proximodistal limb patterning. Our analysis of RA-regulated genes supports a role for transient RA gradients in early limb bud in proximal-to-distal patterning in this anamniote model organism.

Bortolanite (IMA 2021–040a), ideally Ca2(Ca1.5Zr0.5)Na(NaCa)Ti(Si2O7)2(FO)F2, is a rinkite-group (seidozerite supergroup) TS-block mineral from Poços de Caldas massif, Minas Gerais, Brazil. Associated minerals are götzenite, nepheline, alkali feldspar, aegirine, natrolite, analcime, and manganoan pectolite. Bortolanite shows complex compositional zoning with götzenite and is visually indistinguishable from götzenite. Bortolanite is pale-yellow to brown and has a vitreous luster. Cleavage is perfect parallel to {100}. Mohs hardness is 5. Bortolanite fluoresces weak yellow under ultraviolet light (100–280 nm). Dcalc. = 3.195 g/cm3. Bortolanite is biaxial (+) with refractive indices (λ = 589.3 nm) α = 1.673(2), β = 1.677(2), γ = 1.690(2); 2Vmeas. = 56(2)°, 2Vcalc. = 58.4°. Chemical analysis by electron microprobe gave Nb2O5 1.07, HfO2 0.20, ZrO2 6.70, TiO2 9.94, SiO2 32.49, Gd2O3 0.12, Nd2O3 0.37, Ce2O3 1.25, La2O3 0.65, Y2O3 0.31, FeO 0.59, MnO 1.46, CaO 31.15, Na2O 8.36, F 6.95, O=F –2.93, sum 98.68 wt.%. The empirical formula based on 18 (O + F) apfu is (Ca1.88La0.03Ce0.06Nd0.02Gd0.01)Σ2[Ca1.56(Zr0.41Hf0.01Y0.02)Σ0.44]Σ2(Na0.85Ca0.15)Σ1(Na1.18Ca0.60Mn0.16Fe2+0.06)Σ2(Ti0.94Nb0.06)Σ1(Si4.07O14)(O1.24F0.76)Σ2F2, Z = 1. The simplified formula is Ca2(Ca,Zr)2Na(Na,Ca)2Ti(Si2O7)2(O,F)2F2. Bortolanite is triclinic, space group P, a 9.615(3), b 5.725(2), c 7.316(2) Å, α 89.91(1), β 101.14(1), γ 100.91(1)°, V 387.7(3) Å3. The crystal structure was refined to R1 = 3.19% on the basis of 2194 unique reflections [F > 4σ(F)] measured using a Bruker APEX II ULTRA three-circle diffractometer with a rotating-anode generator (MoKα), multilayer optics, and an APEX II 4K CCD detector. The crystal structure of bortolanite is a framework of TS (Titanium-Silicate) blocks [structure type B3(RG)], where the TS block consists of HOH sheets (H-heteropolyhedral, O-octahedral). The TS block exhibits linkage and stereochemistry typical for the rinkite group where Ti (+ Nb + Zr) = 1 apfu. The O sheet is composed of Ti-dominant MO(1) octahedra, [8]Na-dominant MO(2) polyhedra and (Na,Ca) MO(3) octahedra. In the H sheet in bortolanite, Si2O7 groups link to (Ca1.5Zr0.5) MH and Ca-dominant AP octahedra. Along a, TS blocks link directly through common edges of MH and AP polyhedra and common vertices of MH, AP, and Si polyhedra of the H sheets belonging to two TS blocks. The name bortolanite is after the locality: the Bortolan quarry in the Poços de Caldas massif, Brazil. Bortolanite is isostructural with three rinkite-group minerals: fogoite-(Y), hainite-(Y), and götzenite.

Pollen development, from unicellular microspores to anthesis, is a complex process involving the coordinated specification, differentiation and functions of different cell types. Key to understanding this development is identifying the genes expressed at precise stages of development. However, transcriptomic studies on pollen prior to anthesis are complicated by the inaccessible nature of pollen developing in the anther and the resistant pollen wall. To assist with understanding gene expression during pollen development we have developed a protocol to perform RNA-Seq on pollen isolated from a single anther (SA RNA-Seq). The protocol involves removing pollen from a single anther for analysis and viewing the remaining pollen to determine the developmental stage. The isolated pollen is chemically lysed and mRNA isolated from the lysate using an oligo-dT column before library preparation. Here, we report on the development and testing of our method and the generation of a transcriptome for three stages of pollen development from Arabidopsis (Arabidopsis thaliana) and two stages from male kiwifruit (Actinidia chinensis). This protocol enables the transcriptome of precise developmental stages of pollen to be analyzed, and uses a small number of plants, potentially facilitating studies that require a range of treatments or the analysis of the first generation of transgenic plants.

Tibia xenograft histology of lapatinib, and cetuximab+trastuzumab treated animals.

FACS gating and the role of RANK expression on prostate sphere formation.

Activation of the EGF receptors EGFR (ErbB1) and HER2 (ErbB2) drives the progression of multiple cancer types through complex mechanisms that are still not fully understood. In this study, we report that HER2 expression is elevated in bone metastases of prostate cancer independently of gene amplification. An examination of HER2 and NF-κB receptor (RANK) coexpression revealed increased levels of both proteins in aggressive prostate tumors and metastatic deposits. Inhibiting HER2 expression in bone tumor xenografts reduced proliferation and RANK expression while maintaining EGFR expression. In examining the role of EGFR in tumor-initiating cells (TIC), we found that EGFR expression was required for primary and secondary sphere formation of prostate cancer cells. EGFR expression was also observed in circulating tumor cells (CTC) during prostate cancer metastasis. Dual inhibition of HER2 and EGFR resulted in significant inhibition of tumor xenograft growth, further supporting the significance of these receptors in prostate cancer progression. Overall, our results indicate that EGFR promotes survival of prostate TIC and CTC that metastasize to bone, whereas HER2 supports the growth of prostate cancer cells once they are established at metastatic sites. Cancer Res; 77(1); 74–85. ©2016 AACR.

Workflow schematic for microfluidic CTC isolation.

Epitopes and staining characteristics of HER2 antibodies.

Fluorescence in situ hybridization analysis of ERBB2.

Supplemental materials, methods and figure legends.

PDF file - 491K, Supplementary Figure 3. Effect of trastazumab on stem cell marker expression. Supplementary Figure 2. Trastuzumab inhibits tertiary tumorsphere formation in luminal cell lines. Supplementary Figure 1. Representative FACS analysis demonstrating an overlap between HER2 expression and ALDH activity. Supplementary Figure 4. Trastuzumab treatment or HER2 gene knockdown reduces tumorsphere formation of MCF7 cells. Supplementary Figure 5. Rank mediated upreglation of HER2 expression in MCF7 cells. Supplementary Figure 6. Elevated HER2 expression in bone metastasis compared to matched primary luminal tumors is not due to HER2 gene amplification. Supplemental Figure 7. No significant differences in HER2 protein expression were found in matched primary tumors and bone metastasis in women with HER-positive breast cancer.

Supplementary Table 1, Figures 1-2 from ADAM15 Supports Prostate Cancer Metastasis by Modulating Tumor Cell–Endothelial Cell Interaction

Using human tumor and cDNA microarray technology, we have recently shown that the ADAM15 disintegrin is significantly overexpressed during the metastatic progression of human prostate cancer. In the current study, we used lentiviral-based short hairpin RNA (shRNA) technology to down-regulate ADAM15 in the metastatic prostate cancer cell line, PC-3. ADAM15 down-regulation dramatically attenuated many of the malignant characteristics of PC-3 cells in vitro and prevented the s.c. growth of PC-3 cells in severe combined immunodeficient (SCID) mice. By inhibiting the expression of ADAM15 in PC-3 cells, we showed decreased cell migration and adhesion to specific extracellular matrix proteins. This was accompanied by a reduction in the cleavage of N-cadherin by ADAM15 at the cell surface. Fluorescence-activated cell sorting analysis revealed reduced cell surface expression of the metastasis-associated proteins αv integrin and CD44. Furthermore, matrix metalloproteinase 9 secretion and activity were abrogated in response to ADAM15 reduction. In an in vitro model of vascular invasion, loss of ADAM15 reduced PC-3 adhesion to, and migration through, vascular endothelial cell monolayers. Using an SCID mouse model of human prostate cancer metastasis, we found that the loss of ADAM15 significantly attenuated the metastatic spread of PC-3 cells to bone. Taken together, these data strongly support a functional role for ADAM15 in prostate tumor cell interaction with vascular endothelium and the metastatic progression of human prostate cancer. [Cancer Res 2008;68(4):1092–9]

Uvite, CaMg3(Al5Mg)(Si6O18)(BO3)3(OH)3(OH), is a new mineral of the tourmaline supergroup. It occurs in the Facciatoia quarry, San Piero in Campo, Elba Island, Italy (42°45′04.55″N, 10°12′50.89″E) at the centre of a narrow (2–3 cm wide) vein composed of aggregates of dark brown to black tourmaline, penetrating (magnesite + dolomite)-rich hydrothermally altered metaserpentinite. Crystals are euhedral and up to 1 cm in size, brown with a vitreous lustre, conchoidal fracture and grey streak. Uvite has a Mohs hardness of ~7½, a calculated density of 3.115 g/cm3 and is uniaxial (–). Uvite has trigonal symmetry, space group R3m, a = 15.9519(10) Å, c = 7.2222(5) Å, V = 1597.3(1) Å3 and Z = 3. The crystal structure was refined to R1 = 1.77% using 1666 unique reflections collected with MoKα X-rays. Crystal-chemical analysis resulted in the empirical crystal-chemical formula $^X ({\rm Ca}_{0.61}{\rm Na}_{{0.35}} \square_{{0.04}})_{\Sigma 1.00}{}^{Y} \left( {{\rm Mg}_{1.50}{\rm Fe}^{2 + }_{0.47} {\rm Al}_{0.71}{\rm Fe}^{3 + }_{0.14} {\rm Ti}_{0.18}} \right)_{\Sigma 3.00}$${}^{Z} \left( {{\rm Al}_{4.54}{\rm Fe}^{3 + }_{0.18} {\rm V}^{3 + }_{0.02} {\rm Mg}_{1.27}} \right)_{\Sigma 6.00}{}^{T}\left[ {{\left( {{\rm Si}_{5.90}{\rm Al}_{0.10}} \right)}_{\Sigma 6.00}{\rm O}_{18}} \right]{\rm } \left( {\rm BO_3} \right)_3^{} {^{\rm O(3)}}\left( {\rm OH} \right)_3{}^{{\rm O}\left( 1 \right)} [\left( {\rm OH} \right)_{0.55}{\rm F}_{0.05}{\rm O}_{0.40}]_{\Sigma 1.00}$which recast in its ordered form for classification purposes is: $$\eqalign{& ^{\rm X} ({\rm Ca}_{0.61}{\rm Na}_{0.35}\squ _{0.04})_{\Sigma 1.00}{}^{\rm Y} \left( {{\rm Mg}_{2.35}{\rm Fe}^{2 + }_{0.47} {\rm Ti}_{0.18}} \right)_{\Sigma 3.00} \cr & {}^{\rm Z} \left( {{\rm Al}_{5.25}{\rm Fe}^{3 + }_{0.32} {\rm V}^{3 + }_{0.02} {\rm Mg}_{0.42}} \right)_{\Sigma 6.00}{}^{\rm T} \left[ {{\left( {{\rm Si}_{5.90}{\rm Al}_{0.10}} \right)}_{\Sigma 6.00}{\rm O}_{18}} \right]{\rm }\left( {\rm BO_3} \right)_3{}^{\rm V} \left( {\rm OH} \right)_3{}^{\rm W} [\left( {\rm OH} \right)_{0.55}{\rm F}_{0.05}{\rm O}_{0.40}]_{\Sigma 1.00}}$$ Uvite is a hydroxy-species belonging to the calcic-group of the tourmaline supergroup. The closest end-member compositions of valid tourmaline species are fluor-uvite and feruvite, to which uvite is related by the substitutions W(OH)– ↔ WF– and YMg2+ ↔ YFe2+, respectively. The occurrence of a solid-solution between uvite and magnesio-lucchesiite, according to the substitution ZMg2+ + W(OH)– ↔ ZAl3+ + WO2–, is supported by experimental data. The new mineral was approved by the IMA–CNMNC (IMA 2019-113). Uvite from Facciatoia formed by the reaction between B-rich fluids, released during the crystallisation process of LCT pegmatites, and the surrounding metaserpentinites, altered by contact metamorphism in the aureole of the Miocene Mt. Capanne monzogranitic pluton.

Hydrogen (δ2H) and oxygen (δ18O) stable isotopes are used to trace fluid sources, metals, and contaminants in the environment and Earth's subsurface. Tourmaline-supergroup minerals provide an opportunity to quantify both δ2H and δ18O from the same grain using in situ analytical techniques (e.g., Secondary Ion Mass Spectrometry – SIMS). These minerals occur in a wide variety of geological environments and have a wide range of chemical compositions. However, large differences in chemical composition are problematic during SIMS analysis, as instrumental mass fractionation (IMF) often varies with the chemical composition of the mineral. Therefore, calibration models derived by analyzing tourmalines of different chemical composition must be developed for accurate analysis by SIMS. Hydrogen and oxygen isotope analysis was done on six reference tourmaline samples using a CAMECA 7f SIMS instrument operating at extreme energy filtering. Spot-to-spot repeatability for tourmalines was in the range 4–5‰ and 0.6–1.0‰ for δ2H and δ18O, respectively. There is a strong correlation between IMF and several elements (B, Si, Ca, Fe, and Fe#). Iron content is the most robust predictor of IMF, and we report two calibration curves for the correction of δ2H and δ18O measured by SIMS using reference tourmaline crystals with different Fe contents, ranging from 0.00 to 14.00 wt.% Fe. This is the first calibration curve used to correct for the fractionation of hydrogen isotope ratios in tourmaline as measured by SIMS. Tourmaline-supergroup minerals require a suite of at least three, with a range of Fe content, to ensure accurate and precise H and O analysis by SIMS. Crystallographic orientation effects were not observed for these tourmalines.

To assess the suitability of newborn hearing screening brochures by evaluating current state-level brochures and pregnant people’s understanding of screening result terminology. In Study 1, state-level brochures were evaluated based on readability, design, picture appropriateness, and use of the word “refer.” In Study 2, pregnant people completed a questionnaire that queried their understanding of and expected anxiety about three newborn hearing screening outcomes (“refer,” “did not pass,” and “pass”). In Study 1, 59 newborn hearing screening brochures were analysed. In Study 2, 43 pregnant people completed surveys during a prenatal appointment. Most of the brochures were found deficient on at least one element. Thirty percent of brochures used the word “refer” to indicate a hearing screening failure; yet, fewer than half of participants understood its meaning. Ratings of expected anxiety were highest in response to the term “did not pass.” Based on four study criteria of brochure suitability, 88% of available state-level newborn hearing screening brochures should be modified to make them readily understandable by a broad educational demographic. Discretion in use of the term “refer” should be made when indicating screening results, because the term is not readily understood.

Shkatulkalite, ideally Na5TiNb2(Si2O7)2O3F(H2O)7, is a lamprophyllite-group (seidozerite supergroup) TS-block mineral from the Lovozero massif, Kola Peninsula, Russia. The crystal structure of shkatulkalite was refined as triclinic, space group P, a 5.464(1), b 7.161(1), c 15.573(1) Å, α 90.00(3), β 95.75(3), γ 90.00(3)°, V 606.3(4) Å3, R1 = 7.26%. The previously given chemical analysis has been modified to better fit the crystal structure: Nb2O5 24.15, TiO2 11.35, SiO2 27.22, BaO 1.15, SrO 2.20, MnO 1.68, CaO 0.46, K2O 0.29, Na2O 14.78, H2O 15.27, F 1.61, O = F −0.68, sum 99.48 wt.%; H2O was determined from structure-refinement results. The empirical formula was calculated on 25.27 (O + F) apfu (in accord with the crystal structure): (Na1.40Sr0.19Ba0.07K0.05)Σ1.71(Na2.86Mn0.10Ca0.07)Σ3.03(Nb1.62Ti1.27Mn0.11)Σ3Si4.03O24.52H15.11F0.75, Z = 1. The ideal structural formula is as follows: Na2Nb2Na3Ti(Si2O7)2O2(FO)(H2O)4(H2O)3. The crystal structure of shkatulkalite [basic structure type B5(LG)] is a combination of a TS (titanium-silicate) block and an I (intermediate) block. The TS block consists of HOH sheets (H-heteropolyhedral, O-octahedral). The TS block exhibits linkage and stereochemistry typical for the lamprophyllite group where Ti (+ Nb + Fe3+ + Mg) = 3 apfu. The O sheet is composed of Ti-dominant MO(1) and Na-dominant MO(2,3) octahedra. In the H sheet in shkatulkalite, Si2O7 groups link to Nb-dominant MH octahedra. The AP site occurs in the plane of the H sheet and splits into AP(1) and AP(2) sites, occupied by Na at 70% and Sr (less Ba and K) at 11%. The I block consists of H2O groups. The I block of shkatulkalite is topologically identical to those in the derivative structures of kazanskyite and nechelyustovite. The structure of the lamprophyllite-group mineral shkatulkalite has a counterpart structure in the murmanite group (Ti = 4 apfu): kolskyite, ideally Na2CaTi4(Si2O7)2O4(H2O)7 [basic structure type B7(MG)]: the two structures have TS blocks of different topology and similar I blocks, mainly occupied by H2O groups.

Shakhdaraite-(Y), ideally ScYNb2O8, is a new mineral from the Leskhozovskaya miarolitic granitic pegmatite at the Shakhdara River, southwestern Pamir (Tajikistan). Shakhdaraite-(Y) occurs mainly as grains from 10 to 150 μm in size in a near-miarolitic pegmatite complex in association with quartz, albite, pyrochlore-microlite, fersmite, and an unnamed Sc-Nb oxide; only one large, single, well-shaped crystal 200 μm long was found in a small cavity with quartz, albite, bertrandite, pyrochlore, and jarosite. Shakhdaraite-(Y) is black to dark-brown, streak is brown. Luster is vitreous semi-metallic. It is brittle with conchoidal fracture. Mohs hardness is 5. VHN100 = 436 kg/mm2. Dcalc. = 5.602 g/cm3. In reflected light, it is light gray and its reflective capacity is moderate to low. Anisotropy is distinct, without color effects. Pleochroism was not observed. Internal reflections are red-brown. Reflectance values were measured in air with SiC as reference material [λ(nm), Rmax, Rmin]: 470, 14.6, 13.9; 546, 14.0, 13.4; 589, 13.9, 13.3; 650, 13.8, 13.1. Electron probe microanalysis (WDS mode, 7 points) gives (wt.%): Nb2O5 50.70; Ta2O5 4.52; TiO2 0.08; WO3 0.79; SnO2 1.54; CaO 1.01; Sc2O3 11.35; MnO 1.38; FeO 0.01; Y2O3 12.00; Ce2O3 0.21; Pr2O3 0.04; Nd2O3 0.27; Sm2O3 0.32; Eu2O3 0.07; Gd2O3 0.86; Tb2O3 0.22; Dy2O3 2.07; Ho2O3 0.29; Er2O3 1.33; Tm2O3 0.35; Yb2O3 2.80; Lu2O3 0.32; PbO 0.24; ThO2 1.90; UO2 3.30, total 97.97. The empirical formula of shakhdaraite-(Y) based on O = 8 apfu (atoms per formula unit) is (Nb1.91Sc0.83Y0.53Ta0.10Mn0.10Ca0.09 Yb0.07U4+0.06Dy0.06Sn0.05Th0.04Er0.03Gd0.02W6+0.02Pb0.01Ce0.01Nd0.01Sm0.01Tb0.01Ho0.01Tm0.01Lu0.01Ti0.01)Σ4.00O8, Z = 2. The simplified formula is Sc(Y,Yb)Nb2O8, where Yb is the dominant lanthanoid. Shakhdaraite-(Y) is monoclinic, space group P2/c, a 9.930(2), b 5.6625(11), c 5.2108(10) Å, β 92.38(3)°, V 292.7(5) Å3, Z = 2. The crystal structure was solved by direct methods [R1 = 0.0269, 878 unique reflections (F > 4σF)]. There are three cation M sites: [6]M(1) = Nb2apfu, [6]M(2) = Sc apfu, and [8]M(3) = Y apfu, ideally M = ScYNb2apfu. The M(1) and M(2) octahedra each form a brookite chain along c. The Y-dominant [8]M(3A) polyhedra form a brookite-like kinked chain, and each M(3A) polyhedron of one brookite-like chain shares two edges with the two M(3A) polyhedra from the adjacent brookite-like chain, thus forming a [Y2O8]10– layer. In the structure of shakhdaraite-(Y), M(1A) and M(2) brookite chains and a layer of [8]-coordinated M(3A) polyhedra alternate along a. Shakhdaraite-(Y) is isostructural with samarskite-(Y), ideally YFe3+Nb2O8. Shakhdaraite-(Y) [Russian Cyrillic: шахдараит-(Y)] is named after its type locality: the valley of the Shakhdara River in the southwest of the Pamir Mountains.

The complexity of global anthropogenic change makes forecasting species responses and planning effective conservation actions challenging. Additionally, important components of a species’ adaptive capacity, such as evolutionary potential, are often not included in quantitative risk assessments due to lack of data. While genomic proxies for evolutionary potential in at-risk species are increasingly available, they have not yet been included in extinction risk assessments at a species-wide scale. In this study, we used an individual-based, spatially explicit, dynamic eco-evolutionary simulation model to evaluate the extinction risk of an endangered desert songbird, the southwestern willow flycatcher (Empidonax traillii extimus), in response to climate change. Using data from long-term demographic and habitat studies in conjunction with genome-wide ecological genomics research, we parameterized simulations that include 418 sites across the breeding range, genomic data from 225 individuals, and climate change forecasts spanning 3 generalized circulation models and 3 emissions scenarios. We evaluated how evolutionary potential, and the lack of it, impacted population trajectories in response to climate change. We then investigated the compounding impact of drought and warming temperatures on extinction risk through the mechanism of increased nest failure. Finally, we evaluated how rapid action to reverse greenhouse gas emissions would influence population responses and species extinction risk. Our results illustrate the value of incorporating evolutionary, demographic, and dispersal processes in a spatially explicit framework to more comprehensively evaluate the extinction risk of threatened and endangered species and conservation actions to promote their recovery.

Video telehealth experienced rapid growth throughout the COVID-19 pandemic in many healthcare sectors, including mental health. The Veterans Health Administration’s video telehealth platform, VA Video Connect, has been widely used to reach veterans who may have experienced difficulty accessing care, such as those living in rural areas or other barriers (e.g., transportation). Implementing VVC requires a multifaceted approach, including training providers on technical skills, increasing access to equipment for providers and veterans, and integrating VVC within the culture and processes of the clinic unit. Prior successful VVC implementation efforts in rural areas have focused on simultaneous one-on-one provider and leadership engagement using implementation facilitation (IF). However, given the rapid need for VVC expansion in light of limits and dangers associated with in-person care during the pandemic, our team developed group facilitation to increase the reach of VVC implementation through IF. Group facilitation combined training in technical and policy elements of VVC with IF with groups of providers from clinic units. This approach was designed to rapidly disseminate the necessary knowledge to conduct VVC combined with collaborative problem solving as a team to improve the ability of the clinical team to sustain VVC. Attendees were asked for feedback on the session through multiple choice and open-ended questions. Participants (N = 26) reported being highly satisfied with the training and reported a high degree of confidence in their ability to use VVC. Based on evaluation data and interview feedback, providers and clinic leaders were satisfied with group facilitation. Group facilitation may be a helpful tool in rapidly training clinical teams to implement and sustain video telemental health.

Objective: This study aims to assess the safety and efficacy of the use of popliteal nerve block (PNB) in the endovascular management of patients with critical limb threatening ischaemia. Design: Single-centre retrospective observational study. Methods: All patients with rest pain who received PNB from March 2018 to August 2021 were included. Pain scores were recorded before and after block using a visual analogue scale (VAS). Requirements for analgesia or sedation, complications related to nerve block, and level of intervention were recorded. Results were compared with a historical cohort of patients prior to implementation of nerve blocks. Results: 68 nerve blocks were performed in 63 patients (M:F 46:17) of mean age 71.7 years (range 43–91). All patients were Fontaine classification III–IV. Sonographically, all nerve blocks were technically successful. The mean VAS pain score was 8.2 pre-block, reducing to 0.3 (p

Species reintroductions are successful when established populations maintain both demographic stability and genetic diversity. Such a result may be obtained by ensuring both structural habitat connectivity and genetic connectivity among reintroduced and remnant populations. Nevertheless, prezygotic barriers such as assortative mating can prevent the flow of genetic material between populations, even when migration between populations is high. Limited gene flow may be particularly relevant for reintroductions that were sourced either from captive-bred populations or from disparate locations in the wild. American martens (Martes americana) have been reintroduced repeatedly in the Upper Midwestern United States in an effort to establish self-sustaining populations. We quantified levels of genetic diversity within and spatial genetic variance among four marten populations during two time periods separated by 10 years. Spatially informed and naïve discriminant analysis of principal components were used to assign individuals to populations. Results indicate that heterozygosity declined and inbreeding coefficients increased between the two collection periods, while genetic structure among populations also increased. Data are consistent with assortative mating contributing to reapportioning of genetic variation. Population assignment tests show that migration among populations is apparent, but admixture (based on cluster membership probabilities) is low and declined over time. Specifically, martens may be successfully dispersing between populations but a lack of admixture indicates a lack of reproductive contributions to genetic diversity by migrants. Because marten reintroductions in this region are well-documented and well-monitored, lessons can be derived from results to inform future reintroductions. We encourage a careful balance of supplementing genetic diversity via augmentation while avoiding translocation of animals from disparate populations that may result in reproductive isolation of migrants. In combination with the maintenance of a functionally connected landscape, this strategy would maximize the likelihood of a successful reintroduction in terms both of demography and genetics.

Marine Protected Areas (MPAs) are key tools in addressing the global decline of sharks and rays, with "marine parks" and "shark sanctuaries" of various configurations established to conserve shark populations. There is also a rapidly growing body of telemetry research used to assess MPA performance in shark protection. However, assessments of MPA efficacy in shark and ray conservation are compromised by inconsistent terminology, a lack of standardised approaches to assess how MPAs contribute to the overall conservation of sharks and rays, and ambiguity about integrating movement data into assessment processes. This paper presents a conceptual framework that standardises key terms and uses the concept of Portfolio Risk to fully describe how an MPA may contribute to shark and ray conservation. The framework also demonstrates how movement data can be integrated into the process and presents eight key questions that provide guidance for applying the framework. Understanding an MPA's contribution to shark and ray protection requires explicit consideration of the assessment scope, MPA type and purpose, the range of existing and potential threats, the species biology and ecology, and management and operational contexts. Ultimately, MPA contributions to shark and ray conservation differ according to a complex set of human and natural factors and interactions which should be carefully considered in MPA design, implementation and evaluation. Article Impact statement: Standardization of key terms and use of the portfolio risk concept describe how protected areas contribute to shark and ray conservation. This article is protected by copyright. All rights reserved.

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease in urgent need of disease biomarkers for the assessment of promising therapeutic candidates in clinical trials. Raman spectroscopy is an attractive technique for identifying disease related molecular changes due to its simplicity. Here, we describe a fibre optic fluid cell for undertaking spontaneous Raman spectroscopy studies of human biofluids that is suitable for use away from a standard laboratory setting. Using this system, we examined serum obtained from patients with ALS at their first presentation to our centre ( n = 66) and 4 months later ( n = 27). We analysed Raman spectra using bounded simplex-structured matrix factorization (BSSMF), a generalisation of non-negative matrix factorisation which uses the distribution of the original data to limit the factorisation modes (spectral patterns). Biomarkers associated with ALS disease such as measures of symptom severity, respiratory function and inflammatory/immune pathways (C3/C-reactive protein) correlated with baseline Raman modes. Between visit spectral changes were highly significant ( p = 0.0002) and were related to protein structure. Comparison of Raman data with established ALS biomarkers as a trial outcome measure demonstrated a reduction in required sample size with BSSMF Raman. Our portable, simple to use fibre optic system allied to BSSMF shows promise in the quantification of disease-related changes in ALS over short timescales.

This paper reviews the concept of governance in protected areas, providing details about nine key principles of governance as they relate to marine protected areas (MPAs). Following a theoretical description of each principle, real-world examples of the principles are presented from the Great Barrier Reef (GBR) Marine Park, where marine governance has evolved over 45 years as part of adaptive management. Examples of good governance in the GBR include the intergovernmental arrangements that enable both federal and state governments to co-operate effectively across adjoining marine jurisdictions. In addition, the application of multiple layers of management adds to an effective integrated approach, considered to be the most appropriate for managing a large MPA. The nine governance principles discussed in the paper are applicable to all MPAs, but how they are applied will vary in dissimilar settings because of differing environmental, social, economic, cultural, and political contexts - clearly, one size does not fit all. The analogy of the nine principles being part of an interlaced or woven ‘lattice’ is also introduced. Collectively the lattice is stronger than any individual principle, and together all principles contribute to the totality of effective governance. The paper provides information for those involved in MPA management who are keen to understand marine governance and how it might apply to their MPA, recognising there will be differences in how the principles will apply.

The research-practice gap is an ongoing concern for sport and exercise science researchers. Despite ongoing efforts to ‘bridge’ the gap between research and practice, a know-do gap remains. Drawing...

Removal of non-native fish populations can be crucial to the conservation of native species, but often presents a complex challenge for managers. The goal of Trojan Y chromosome (TYC) programs is to skew the non-native sex ratio until only males remain, leading to eradication. We present results from a simulation model used to explore effects of alternative management approaches on an in-progress mechanical removal and TYC program to eradicate non-native brook trout (Salvelinus fontinalis). Simulation results indicated that stocking fingerling YY males (∼137 mm) was more effective than stocking catchable-sized YY males (∼230 mm), although questions about intercohort competition warrant further investigation. Increasing the proportion of mature fingerling YY males reduced treatment time by increasing the number of YY male spawners and increasing density-dependent mortality on young, mature wild brook trout. Maximizing the spatial distribution of YY male releases may be crucial to program success but is also dependent upon immediate dispersal movements. Principles derived from our results can be broadly applied to the management of other aquatic invaded systems using TYC programs to eradicate non-native species.

Introduction Pre-eclampsia (PE) is a dangerous placental condition that can lead to premature labour, seizures and death of mother and infant. Several studies have identified altered placental DNA methylation in PE; however, there is widespread inconsistency between studies and most findings have not been replicated. This study aimed to identify and validate consistent differences in methylation across multiple PE cohorts. Methods Seven publicly available 450K methylation array datasets were analysed to identify consistent differentially methylated positions (DMPs) in PE. DMPs were identified based on methylation difference (≥10%) and significance (p-value ≤ 1 × 10−7). Targeted deep bisulfite sequencing was then performed to validate a subset of DMPs in an additional independent PE cohort. Results Stringent analysis of the seven 450K datasets identified 25 DMPs (associated with 11 genes) in only one dataset. Using more relaxed criteria confirmed 19 of the stringent 25 DMPs in at least four of the remaining six datasets. Targeted deep bisulfite sequencing of eight DMPs (associated with three genes; CMIP, ST3GAL1 and DAPK3) in an independent PE cohort validated two DMPs in the CMIP gene. Seven additional CpG sites in CMIP were found to be significantly differentially methylated in PE. Discussion The identification and validation of significant differential methylation in CMIP suggests that the altered DNA methylation of this gene may be associated with the pathogenesis of PE, and may have the potential to serve as diagnostic biomarkers for this dangerous condition of pregnancy.

To examine the association of alcohol consumption and type of alcoholic beverage with incident cataract surgery in 2 large cohorts.Longitudinal, observational study.We included 469 387 participants of UK Biobank with a mean age of 56 years and 23 162 participants of European Prospective Investigation of Cancer (EPIC)-Norfolk with a mean age of 59 years.Self-reported alcohol consumption at baseline was ascertained by a touchscreen questionnaire in UK Biobank and a food-frequency questionnaire in EPIC-Norfolk. Cases were defined as participants undergoing cataract surgery in either eye as ascertained via data linkage to National Health Service procedure statistics. We excluded participants with cataract surgery up to 1 year after the baseline assessment visit or those with self-reported cataract at baseline. Cox proportional hazards models were used to examine the associations of alcohol consumption with incident cataract surgery, adjusted for age, sex, ethnicity, Townsend deprivation index, body mass index (BMI), smoking, and diabetes status.Incident cataract surgery.There were 19 011 (mean cohort follow-up of 95 months) and 4573 (mean cohort follow-up of 193 months) incident cases of cataract surgery in UK Biobank and EPIC-Norfolk, respectively. Compared with nondrinkers, drinkers were less likely to undergo cataract surgery in UK Biobank (hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.85-0.93) and EPIC-Norfolk (HR, 0.90; 95% CI, 0.84-0.97) after adjusting for covariables. Among alcohol consumers, greater alcohol consumption was associated with a reduced risk of undergoing cataract surgery in EPIC-Norfolk (P0.001), whereas a U-shaped association was observed in the UK Biobank. Compared with nondrinkers, subgroup analysis by type of alcohol beverage showed the strongest protective association with wine consumption; the risk of incident cataract surgery was 23% and 14% lower among those in the highest category of wine consumption in EPIC-Norfolk and UK Biobank, respectively.Our findings suggest a lower risk of undergoing cataract surgery with low to moderate alcohol consumption. The association was particularly apparent with wine consumption. We cannot exclude the possibility of residual confounding, and further studies are required to determine whether this association is causal in nature.

Objective Prostaglandins (PGs) use for cervical ripening with small for gestational age (SGA) fetuses is controversial since it remains uncertain if use increases the chance of cesarean delivery (CD). We aimed to assess the association between PG use for cervical ripening and mode of delivery between SGA and appropriate for gestational age (AGA) neonates. Study Design Secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b), a prospective observational cohort study of 10,038 nulliparas. We included women undergoing induction with nonanomalous fetuses in the cephalic presentation. Women with >2 cm cervical dilation or prior uterine scar were excluded. We assessed the association of PG use with CD among women with SGA and AGA neonates. SGA was defined as birth weight Results Among 2,353 women eligible, PGs were used in 54.8%, SGA occurred in 15.1%, and 35.0% had CD. The association between PG use and CD differed significantly (interaction p = 0.018) for SGA versus AGA neonates; CD occurred more often in SGA neonates exposed to PGs than not (35 vs. 22%, p = 0.009). PG use was not associated with CD among AGA neonates (36 vs. 36%, p = 0.8). This effect remained significant when adjusting for body mass index, race/ethnicity, and cervical dilation. Among SGA neonates, CD for “nonreassuring fetal status” was similar between PG groups. Among SGA neonates, PG use was not associated with adverse neonatal outcomes or postpartum hemorrhage but had a higher rate of chorioamnionitis (7.0 vs. 2.1%, p = 0.048). Conclusion PG use was associated with a higher rate of CD in SGA but not AGA neonates; however, further studies are needed before PG use is discouraged with SGA neonates. Key Points