Optical coherence tomography for the non-invasive investigation of the microstructure of ancient Egyptian faience

Optical Coherence Tomography (OCT) is a non-invasive subsurface 3D imaging technique based on the Michelson interferometer. The non-invasive nature of OCT and its speed of acquisition makes it possible to image large volumes of intact objects to yield a complete overview of the microstructure. The production methods for ancient Egyptian faience were first investigated using scanning electron microscopy (SEM) imaging of the microstructure in polished sections and microprobe analysis of the composition of the glass phases. These studies were based on original Egyptian faience objects and laboratory reproductions of faience beads made using three different production methods. The microstructure of the same laboratory samples and the Egyptian faience objects from the British Museum Research Laboratory Collection are re-examined using OCT

Outcomes by Sex Following Treatment Initiation With Atazanavir Plus Ritonavir or Efavirenz With Abacavir/Lamivudine or Tenofovir/Emtricitabine

Background. We aimed to evaluate treatment responses to atazanavir plus ritonavir (ATV/r) or efavirenz (EFV) in initial antiretroviral regimens among women and men, and determine if treatment outcomes differ by sex

Population policies and education: exploring the contradictions of neo-liberal globalisation

The world is increasingly characterised by profound income, health and social inequalities (Appadurai, 2000). In recent decades development initiatives aimed at reducing these inequalities have been situated in a context of increasing globalisation with a dominant neo-liberal economic orthodoxy. This paper argues that neo-liberal globalisation contains inherent contradictions regarding choice and uniformity. This is illustrated in this paper through an exploration of the impact of neo-liberal globalisation on population policies and programmes. The dominant neo-liberal economic ideology that has influenced development over the last few decades has often led to alternative global visions being overlooked. Many current population and development debates are characterised by polarised arguments with strongly opposing aims and views. This raises the challenge of finding alternatives situated in more middle ground that both identify and promote the socially positive elements of neo-liberalism and state intervention, but also to limit their worst excesses within the population field and more broadly. This paper concludes with a discussion outling the positive nature of middle ground and other possible alternatives

Immune complex-mediated co-ligation of the BCR with FcγRIIB results in homeostatic apoptosis of B cells involving Fas signalling that is defective in the MRL/Lpr model of systemic lupus erythematosus

Negative regulation of B cell activation by cognate immune complexes plays an important homeostatic role in suppressing B cell hyperactivity and preventing consequent autoimmunity. Immune complexes co-ligate the BCR and FcγRIIB resulting in both growth arrest and apoptosis. We now show that such apoptotic signalling involves induction and activation of p53 and its target genes, the pro-apoptotic Bcl-2 family members, Bad and Bid, as well as nuclear export of p53. Collectively, these events result in destabilisation of the mitochondrial and lysosomal compartments with consequent activation and interplay of executioner caspases and endosomal-derived proteases. In addition, the upregulation of Fas and FasL with consequent activation of caspase 8-dependent death receptor signalling is required to facilitate efficient apoptosis of B cells. Consistent with this role for Fas death receptor signalling, apoptosis resulting from co-ligation of the BCR and FcγRIIB is defective in B cells from Fas-deficient MRL/MpJ-Faslpr mice. As these mice develop spontaneous, immune complex-driven lupus-like glomerulonephritis, targeting this FcγRIIB-mediated apoptotic pathway may therefore have novel therapeutic implications for systemic autoimmune disease

Less Bone Loss With Maraviroc- Versus Tenofovir-Containing Antiretroviral Therapy in the AIDS Clinical Trials Group A5303 Study

Background. There is a need to prevent or minimize bone loss associated with antiretroviral treatment (ART) initiation. We compared maraviroc (MVC)- to tenofovir disoproxil fumarate (TDF)–containing ART

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Shifting materials: variability, homogeneity and change in the beaded ornaments of the Western Zhou

Academic interest in the elaborate bead assemblages recovered from graves of the Western Zhou elite has grown in recent years. Beads and beaded ornaments have been seen as both markers of external contact and evidence of change in the Zhou ritual system. Recent study of these bead assemblages, however, indicates that they may also have reflected shifting political circumstances. The use of different bead materials and forms suggests a trend to centralised production and control of manufacture, particularly from the later tenth century BC. The authors correlate a move towards readily manufactured materials with evidence for widespread elite intermarriage, and consider a possible tension between production and the socio-political strategies of the Zhou court

Data from: A species' response to spatial climatic variation does not predict its response to climate change

<p>The dominant paradigm for assessing ecological responses to climate change assumes that future states of individuals and populations can be predicted by current, species-wide performance variation across spatial climatic gradients. However, if the fates of ecological systems are better predicted by past responses to <em>in situ</em> climatic variation through time, this current analytical paradigm may be severely misleading. Empirically testing whether spatial or temporal climate responses better predict how species respond to climate change has been elusive, largely due to restrictive data requirements. Here we leverage a newly collected network of ponderosa pine tree-ring time series to test whether statistically inferred responses to spatial versus temporal climatic variation better predict how trees have responded to recent climate change. When compared to observed tree growth responses to climate change since 1980, predictions derived from spatial climatic variation were wrong in both magnitude and direction. This was not the case for predictions derived from climatic variation through time, which were able to replicate observed responses well. Future climate scenarios through the end of the 21st century exacerbated these disparities. These results suggest that the currently dominant paradigm of forecasting the ecological impacts of climate change based on spatial climatic variation may be severely misleading over decadal to centennial timescales.</p><p>Funding provided by: American Philosophical Society<br>Crossref Funder Registry ID: https://ror.org/04egvf158<br>Award Number: </p><p>Funding provided by: Brown University<br>Crossref Funder Registry ID: https://ror.org/05gq02987<br>Award Number: </p><p>Funding provided by: Brown University<br>Crossref Funder Registry ID: https://ror.org/05gq02987<br>Award Number: </p><p>Funding provided by: National Science Foundation<br>Crossref Funder Registry ID: https://ror.org/021nxhr62<br>Award Number: MSP-ECA 1802893</p><p>Study species</p> <p>Ponderosa pine (<em>Pinus ponderosa sensu lato</em>) is widely distributed in western North America throughout a highly disjunct range that encompasses a tremendous breadth of climatic conditions, with mean annual temperatures ranging from 0 to 15 degrees Celsius and 200 to 2100 millimeters of mean annual cumulative precipitation (Figure 1).The most commonly used taxonomy recognizes two varieties of<em> P. ponderosa,</em> <em>var. scopulorum</em> and <em>var. ponderosa</em> – the interior and Pacific varieties, respectively (24).  The most recent molecular work has found evidence of more complex taxonomic structuring within ponderosa pine (17, 18), indicating at least four lineages. However, these finer taxonomic divisions do not seem to align with differences in climate sensitivities (19, 55), and do not yet have precisely defined geographic boundaries, preventing the confident assignment of populations to these taxonomic units without genetic analyses. Hence the analyses presented in the main body of this manuscript treat the <em>P. ponderosa</em> as a single unit, with supplementary analyses of how the Pacific – interior distinction impacts climate responses.</p> <p>Tree-ring data</p> <p>Data collection</p> <p>We selected study populations from across the distribution of <em>P. ponderosa s.l.</em>, following the niche-based methodology proposed by Perret & Sax (2021; (20)). We used curated and taxonomically verified botanical records compiled in the Conifer Database (82) to bound the climate space occupied by <em>P. ponderosa s.l.</em> across its geographic distribution. This climate space was defined by a set of seven climatic variables previously used to model the climatic niches of pines and other conifer species (20, 83). We limited site selection to public lands managed by the United States Forest Service or the Bureau of Land Management. Further criteria were that sites were free of obvious recent disturbance (e.g., timber harvest, thinning or other stand management, recent fire), were a minimum of one kilometer from high-traffic roadways, and were not located on either particularly steep slopes or along drainages. Wherever possible, we selected sites such that they corresponded with one of the Conifer Database botanical records used to build the species' climatic niche model. This site selection procedure resulted in 24 study sites, spread across the states of Arizona, California, Colorado, Idaho, Montana, Oregon, and Montana (Figure 1, Table S1).</p> <p> We used a consistent plot- and survey-based approach to collect tree-ring samples at each study site. Specifically, we established a 25-m by 25-m square plot in a representative portion of the stand at each site. Within this plot, we measured each ponderosa pine's bole diameter at 1.4 m above ground level (i.e., diameter at breast height, DBH), assessed its general condition and vigor, recorded the presence or absence of new cones, and recorded any evidence of pathogens (e.g., sap flows, needle blight). Using a Haglöf increment borer, we collected two 4.3 mm-diameter cores from each tree greater than 15 cm DBH in the plot. One core was collected at breast height (140 cm), and the other was collected as close to the ground as possible given available equipment and the individual tree's setting. In cases where there were fewer than 15 suitable trees on a plot, we sampled additional trees at increasing distances from the plot center. For 10 sites, we could not establish a fixed plot due either to excessive understory growth or site terrain characteristics. For these sites, trees were sampled at increasing distances from the intended plot location (i.e., an n-tree sampling design; 72). Sampling was conducted during the 2018 growing season between June and October.</p> <p>Sample preparation</p> <p> All increment cores were mounted, sanded, and visually cross-dated according to standard dendrochronological methods (85). We then measured the width in millimeters of each growth ring in every core sample using 2400 dpi digital scans and the computer program CooRecorder (86). We verified year assignments of the measured tree ring series using CDendro (87) and the 'dplR' package in R 3.6.3 (88, 89). Specifically, we used 20-year lagged inter-series correlations to identify dating and measurement errors across all series per site. These errors were iteratively identified and corrected until all inter-series correlations between 20-year segments were above 0.60. Both core samples for each tree were used during visual and statistical cross-dating, but only samples extracted from breast height were retained for growth analyses. For one site, located outside of Show Low, Arizona, a high rate of missing and false rings prevented confident assignment of a year of formation to growth rings. This site was excluded from all subsequent analyses. We used field-measured DBH for each tree to convert these ring width timeseries to annual basal area increments (BAI), a procedure that controls for the influence of increasing tree bole diameter on annual ring widths (90). In total, this yielded 360 tree growth time series from 23 sites (Table S1).</p&gt