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Background: Sentinel node-based management (SNBM) is the international standard of care for early breast cancer that is clinically node-negative based on randomised trials comparing it with axillary lymph node dissection (ALND) and reporting similar rates of axillary recurrence (AR) without distant disease. We report all ARs, overall survival, and breast cancer-specific survival at 10-years in SNAC1. Methods: 1.088 women with clinically node-negative, unifocal breast cancers 3 cm or less in diameter were randomly assigned to either SNBM with ALND if the sentinel node (SN) was positive, or to SN biopsy followed by ALND regardless of SN involvement. Results: First ARs were more frequent in those assigned SNBM rather than ALND (11 events, cumulative risk at 10-years 1·85%, 95% CI 0·95–3.27% versus 2 events, 0·37%, 95% CI 0·08–1·26%; HR 5·47, 95% CI 1·21–24·63; p = 0·013). Disease-free survival, breast cancer-specific survival, and overall survival were similar in those assigned SNBM versus ALND. Lymphovascular invasion was an independent predictor of AR (HR 6·6, 95% CI 2·25–19·36, p

Abstract Large-scale offshore wind farms are a critical component of the worldwide climate strategy. However, their developments have been opposed by the fishing industry because of concerns regarding the impacts of pile driving vibrations during constructions on commercially important marine invertebrates, including bivalves. Using field-based daily exposure, we showed that pile driving induced repeated valve closures in different scallop life stages, with particularly stronger effects for juveniles. Scallops showed no acclimatization to repetitive pile driving across and within days, yet quickly returned to their initial behavioral baselines after vibration-cessation. While vibration sensitivity was consistent, daily pile driving did not disrupt scallop circadian rhythm, but suggests serious impacts at night when valve openings are greater. Overall, our results show distance and temporal patterns can support future mitigation strategies but also highlight concerns regarding the larger impact ranges of impending widespread offshore wind farm constructions on scallop populations.

Power TAC (www.powertac.org) is a discrete-time competitive simulation that models a retail electricity market. Since 2012 it has been the foundation of an annual competition, challenging teams from around the world to build autonomous trading agents that communicate with the simulation over the internet. These “retail brokers” offer energy services to customers through tariff contracts, and must then serve those customers by trading in a wholesale market. Hourly differences between wholesale market positions and net consumption by their subscribed customers must be cleared in a local balancing market using a combination of demand response and wholesale balancing energy. The simulation server is open source and highly modular, designed to be accessible to inexperienced student developers. It makes heavy use of annotations and aspect-oriented programming to achieve consistency and ensure that all important events are recorded, allowing simulations to be re-played and analyzed in depth.

Summary Desulfovibrio desulfuricans reduces Pd(II) to Pd(0)‐nanoparticles (Pd‐NPs) which are catalytically active in 2‐pentyne hydrogenation. To make Pd‐NPs, resting cells are challenged with Pd(II) ions (uptake), followed by addition of electron donor to promote bioreduction of cell‐bound Pd(II) to Pd(0) (bio‐Pd). Application of radiofrequency (RF) radiation to prepared 5 wt% bio‐Pd catalyst (60 W power, 60 min) increased the hydrogenation rate by 70% with no adverse impact on selectivity to cis‐2‐pentene. Such treatment of a 5 wt% Pd/carbon commercial catalyst did not affect the conversion rate but reduced the selectivity. Lower‐dose RF radiation (2–8 W power, 20 min) was applied to the bacteria at various stages before and during synthesis of the bio‐scaffolded Pd‐NPs. The reaction rate (μ mol 2‐pentyne converted s‐1) was increased by ~threefold by treatment during bacterial catalyst synthesis. Application of RF radiation (2 or 4 W power) to resting cells prior to Pd(II) exposure affected the catalyst made subsequently, increasing the reaction rate by 50% as compared to untreated cells, while nearly doubling selectivity for cis 2‐pentene. The results are discussed with respect to published and related work which shows altered dispersion of the Pd‐NPs made following or during RF exposure.

Powder deposition and accumulation on walls of spray drying chamber has been known to impact spray drying processes, resulting in lower yield, frequent shutdowns, and downtimes. Critical factors that impact the extent and rate of wall deposition have been studied extensively in the chemical and food industry. In this paper, we present an atypical process yield issue wherein acceptable yield is obtained during the first batch of spray drying but undergoes significant yield loss in consecutive batches. Through understanding the interplay of the process, material properties, and equipment, we identify key mechanisms that are playing a role in causing the process yield issue. These mechanisms include surface roughness of the inner wall of the spray dryer, variation in gas flow due to the introduction of process analytical technology, start-up and shutdown operating parameters that expose the wall deposited powder from the prior batch to temperatures close to the onset of glass transition temperature and cause depression of its glass transition temperature. These factors result in more wall accumulation and impact the yield in subsequent batches. By correcting for most of these factors, the yield reduction issue was mitigated, and processing efficiency was improved.

The RADxSM Tech program was a unique funding and support mechanism to accelerate the market introduction of diagnostic tests for SARS-CoV-2, the virus that causes COVID-19. In addition to providing funding, the RADx Tech program provided unprecedented levels of non- monetary support. Applications were evaluated using a deep dive process which involved a 1- to 2-week intensive collaboration between the applicant and a team of experts from RADx Tech. The result of this deep dive was a very comprehensive understanding of the potential and risks associated with the proposed work, which was far beyond what can typically be understood in a written grant application. This detail allowed the deep dive team to provide a better-informed recommendation on how to proceed. In some instances, the recommendation was made to not fund the project; in other cases, the recommendation was made to provide the applicant with more funding or support to help maximize their probability of success. After the deep dive, the project moved to a Work Package 1 (WP1) phase that focused on further de-risking. The same RADx Tech team that conducted the deep dive also worked with the applicant through the WP1 phase of the program. This allowed for joint responsibility of the work with the common goal of rapid, successful product introduction.

RADxSM Tech's mission is to rapidly accelerate deployment of SARS-CoV-2 tests and could not utilize typical grant application and review processes that can run 4 to 6 months. Instead, RADx Tech leveraged methodologies developed by CIMIT and utilized by POCTRN as described further in this special issue. RADx Tech uses a multi-stage review with two review panels, a Viability Panel and a Steering Panel, that are supported by subject matter experts and a Deep Dive team. Members of the panels have extensive commercialization and business experience in addition to scientific and technical knowledge. The Viability Panel is responsible for assessing whether the proposal is a good fit with the RADx Tech Program and whether it should be recommended to move into a Deep Dive. Less detailed information is requested in the application than a typical SBIR application since the application is refined and details added during the Deep Dive. The Steering Panel reviews the results from the Deep Dive and decides whether to recommend further funding. Everyone on the Viability Panel and Steering Panel reviews every application, thereby providing consistency and context for the reviewers. Utilization of an “assess, improve, and then select” process with review panels comprised of highly experienced review panel members has resulted in improved timing, efficiency, and effectiveness of reviews and has the potential to be extensible beyond RADx Tech.

Patients with imaging findings concerning for subarachnoid hemorrhage, however, with no evidence of hemorrhage following autopsy or cerebrospinal fluid testing are diagnosed with having pseudo-subarachnoid hemorrhage. A 73-year-old female presented to the emergency department with altered mental status one day after undergoing a lumbar epidural steroid injection at an outside hospital; a noncontrast computed tomography scan of the head revealed evidence of diffuse hyperdensity within the subarachnoid space concerning for subarachnoid hemorrhage. The patient underwent magnetic resonance imaging which demonstrated diffuse opacification of the cerebrospinal fluid spaces with gadolinium and the diagnoses of pseudo-subarachnoid hemorrhage and gadolinium encephalopathy were made. The combination of the neurologic symptoms related to gadolinium encephalopathy and the radiographic findings of pseudo-subarachnoid hemorrhage can create a clinical presentation nearly identical to ruptured aneurysmal subarachnoid hemorrhage. Patient history, magnetic resonance imaging findings, and temporal changes in computed tomography provide vital tools in establishing a diagnosis of pseudo-subarachnoid hemorrhage, especially after an iatrogenic intrathecal contrast administration.

Abstract In the battle against climate change, electrification plays an increasingly large role in our society. The growing use of electricity networks requires advanced coordination mechanisms to avoid the tragedy of the commons. In this paper, we explore the effects of optimum time-dependent pricing (TDP) on supplier surplus within electricity markets, using a parameterized optimization model. Varying not only the prices themselves, but also their announcement horizon, we show how the suppliers’ optimal decision depends on risk aversion, forecasting quality, and end-user flexibility. The inclusion of procurement risk in our model shows that TDP can be beneficial for suppliers when they want to actively manage risk, even if expected profits are lower. At the same time, the shifting of end-user demand to low-cost times reduces the overall system cost, and potentially carbon emissions.

“Drugs” have been regulated at the international level since 1912, while cannabis has been specifically regulated since 1925. Contemporary local, national, and international cannabis regulations are now diverging, with some jurisdictions legalising its recreational production, sale and consumption. This essay explores the legal and historical complexity and contingencies around the development of international cannabis regulations and prohibitions. It highlights that the global drug control system was not solely focused on prohibition and instead was a complex mix of regulations underpinned by frequently ill-defined and unclear prohibitions. It argues that the international drug control system should not serve as a bar to national-level reforms and that the two can continue to coexist. The essay favors a flexible, functional and pragmatic interpretation and implementation of the system as the most likely and indeed preferred outcome of international cannabis policy reforms.

This article details a correction to the article: Diskul, M.L.D., Collins, J. and Brombacher, D., 2021. Drugs and Development in the Urban Setting—Expanding Development-Oriented Interventions Beyond Illicit Drug Crop Cultivation. Journal of Illicit Economies and Development, 2(2), pp.80–90. DOI: http://doi.org/10.31389/jied.73

This article breaks new conceptual ground by questioning orthodox interpretations of nation state agency in the global drug wars. Specifically, it challenges the David vs. Goliath conception of Colombia as a passive, client state simply abiding to the United States’ hegemonic war on drugs. It provides the first published analysis of Colombia’s leadership during the UN General Assembly Special Session on Drugs (UNGASS) in 2016. It argues that the UN served as a useful forum for Colombia’s displacement of state building dilemmas, including drug control, and that Bogota utilised the UN as a proxy negotiating mechanism with the US and other international donors.

Abstract Background Heterotopia of pancreatic tissue in the thorax and mediastinum is uncommon, although, a common developmental anomaly in the gastrointestinal tract where the aberrant tissue is a component of gastrointestinal duplication cysts, intralobular pulmonary sequestration or teratomas. Case presentation We report a case of an ectopic pancreas located in a giant mediastinal cyst in a 2-year old girl who presented with severe dyspnoea due to external compression of the intra-thoracic structures, mainly the right main bronchus. Surgical resection was carried out with complete relief of symptoms. The cyst was confirmed histopathologically to contain pancreatic tissue. Literature review showed that this is an uncommon presentation hence the need to report the case. Conclusion Heterotopia of the pancreas although, an uncommon occurrence in the thorax and mediastinum, should be considered when dealing with cystic lesions of the mediastinum and surgery plays an important role in its management. Trial registration JUTH/DCS/ADM/127/XXV/203. Registered 2nd September 2018.

This study evaluated the effect of three N fertilization levels 60 (low), 120 (medium), and 180 (high) kg N ha−1 and soil moisture content gradients created by a line-source sprinkler on the expression of plasticity in lateral root branching and dry matter production (DMP) of upland new rice for Africa (NERICA) 1 and 4. There were no significant differences in DMP between NERICA 1 and 4 under well-watered, mild drought, and severe drought conditions regardless of N level. In contrast, under moderate drought (12–21% v/v of soil moisture content [SMC] in 2011 and 16–24% v/v of SMC in 2012), NERICA 1 had significantly higher shoot dry weight, total root length (TRL), lateral root length, and branching index than NERICA 4 at medium and high N; however, there was no significant difference between the two NERICAs in DMP at low N. TRL of NERICA 1 was significantly higher under moderate drought than well-watered conditions, but only with medium and high N. Regardless of N level, moderate drought did not enhance NERICA 4’s root system. Thus, NERICA 1’s root system exhibited plastic development, promoting lateral root branching at medium and high N. These morphological changes were associated with the greater DMP in NERICA 1 than NERICA 4 under moderate drought, whereas the lack of such plasticity at low N meant genotypic differences in DMP were obscured. Our findings implied that N application can improve upland NERICA productivity under moderate drought conditions, but differences in variety and field conditions may influence efficacy.

This special issue of the Journal of Illicit Economies and Development builds on a growing, multifaceted research and policy agenda that advances development perspectives of illicit economies in the Global South. Conventional policy discourses have typically framed this issue as a security problem, drawing direct and often simplistic causalities with underdevelopment. Illicit economies frequently drive violence, corruption, exploitation and failures in governance, for example. However, for many communities living in poverty and conflict-affected areas across the globe, involvement in illicit economic activity can also ameliorate the immediate problems they face. Illicit economies may provide vital sources of livelihood and underpin stable political orders and socio-economic development at the margins of the state. Broad, securitised policy responses may cause more harm than good in such contexts. Scoping the complex relationship between illicit economies and development, this introductory article outlines key themes of the special issue.

The Special Issue proposes ‘urban peace’ as a way of thinking about policy responses to the dynamics of crime, violence, and exclusion that are associated with illicit economies. This approach builds on the notions of connectedness, proximity and trust between individuals, different segments of society, and divided urban spaces. It stands in contrast to the emphasis on separation, distance, and enmity associated with securitized, zero-tolerance, or counter-terror approaches. The notion of ‘urban peace’ also emphasises that more pragmatic approaches are necessary to provide leadership on reducing violence and exclusion and on expanding economic opportunities in cities.

This paper highlights the complex and contested relationship between drugs and development policies globally. It uses a recent experience in Thailand to showcase the link between drugs and development policies while highlighting the difficult international terrain for forging a common United Nations (UN) position. It examines the challenging transition underway within Thailand as practitioners of rural development policies in drug crop affected regions seek to translate the lessons of traditional ‘alternative development’ to urban and borderland areas affected by drug trafficking, arguing that many of the underlying principles are the same. It provides a practitioner-led overview of the recent experiences of Thailand and the global drug debates. It then takes a step into the literature on peacebuilding, examining the possible positioning of drugs and development debates relative to the field of peacebuilding studies. It concludes by highlighting the numerous areas of overlap between the new drugs and development debates and existing peacebuilding discussions. Publisher’s Note: A correction article relating to this paper has been published and can be found at https://jied.lse.ac.uk/articles/10.31389/jied.97/.

Summary: Nanostructured porous silicon materials have recently advanced as hosts for Li-metal plating. However, limitations involve detrimental silicon self-pulverization, Li-dendrites, and the ability to achieve wafer-level integration of non-composite, pure silicon anodes. compo. Herein, full cells featuring low-resistance, wafer-scale porous crystalline silicon (PCS) anodes are embedded with a nanoporous Li-plating and diffusion-regulating surface layer upon combined wafer surface cleaning (SC) and anodization. LL Lithiophilic surface formation is illustrated via correlation of surface groups and X-ray structure. Low-cost SC-PCS anodes require no composite formulation, and pre-lithiation enables sustainable Li-metal plating/stripping on the lithiophilic surface and in SC-PCS bulk nanostructure. Anodization time and C-rate determined competitive full cell performance: NMC811 | 4800 s SC-PCS: 195 mAh/g (99.9% coulombic efficiency [C.E.], C/3, 50 cycles), 165 mAh/g, 587 Wh/kg (97.1% C.E., C/3 and C/2 rate, 350 cycles), 24 Ω∗cm2 SC-PCS-resistivity (900 cycles); 160 μm LCO | 500 s SC-PCS: 102 mAh/g (94.1% C.E., 1C, 350 cycles).

This paper challenges contemporary policy conceptions on the historical relationship between drugs and development policies. It uses a historical analysis to examine the interaction of drugs, governance, security, welfare and economic development policies within drug producing contexts in Asia, from colonialism through the period of decolonisation. It highlights that although modern narratives of drugs and development tend to view the latter as new and involving even immediately contemporary innovations for dealing with the outcomes of drug economies and drug policies, the historical reality is much more complex. Managing drugs and development was a fundamental historical process of state regulation, control and the settling of geographical boundaries, both economically and physically. This chapter posits two foundational ideas. First, the issues of drugs and development have always been fundamentally linked, from the globalisation of trade through mercantilist imperial policies, state formation, the limits of governance, the distribution of economic gains, and political economy outcomes stretching from the local to the global. Drugs, licit and illicit, have therefore always been an issue of economic development. Second, policymakers have long recognised and developed state responses based on the above reality. While not going under its now ‘official’ title, many of the principles of ‘alternative development’ have been ingrained in policy responses and limitations over the past several centuries.

Real-world vehicle and engine activity data were collected from 90 heavy-duty vehicles in California, United States, most of which have engine model year 2010 or newer and are equipped with selective catalytic reduction (SCR). The 90 vehicles represent 19 different groups defined by a combination of vocational use and geographic region. The data were collected using advanced data loggers that recorded vehicle speed, position (latitude and longitude), and more than 170 engine and aftertreatment parameters (including engine load and exhaust temperature) at the frequency of one Hz. This article presents plots of real-world exhaust temperature and engine load distributions for the 19 vehicle groups. In each plot, both frequency distribution and cumulative frequency distribution are shown. These distributions are generated using the aggregated data from all vehicle samples in each group.

The article proposes a unified least squares method to estimate the receiver operating characteristic (ROC) parameters for continuous and ordinal diagnostic tests, such as cancer biomarkers. The method is based on a linear model framework using the empirically estimated sensitivities and specificities as input “data.” It gives consistent estimates for regression and accuracy parameters when the underlying continuous test results are normally distributed after some monotonic transformation. The key difference between the proposed method and the method of Tang and Zhou lies in the response variable. The response variable in the latter is transformed empirical ROC curves at different thresholds. It takes on many values for continuous test results, but few values for ordinal test results. The limited number of values for the response variable makes it impractical for ordinal data. However, the response variable in the proposed method takes on many more distinct values so that the method yields valid estimates for ordinal data. Extensive simulation studies are conducted to investigate and compare the finite sample performance of the proposed method with an existing method, and the method is then used to analyze 2 real cancer diagnostic example as an illustration.

The Jewish apocalyptic literature that first appears in the Hellenistic period and continues into the Common Era developed a radically novel view of the future. As formulated in the apocalypse of 4 Ezra about the end of the first century CE, the Most High created not one world but two. This world must be utterly destroyed and replaced by a new creation. This view of the future is inherited in the New Testament, most strikingly in the Book of Revelation. It would have enormous but ambivalent implications for western history. On the one hand, it threatened to undermine the importance of working for a better life in this world. On the other hand, it offered hope to those who would otherwise have no hope at all.

Mesenchymal stem cells (MSC) are capable of multipotent differentiation into connective tissues and as such are an attractive source for autologous cell-based regenerative medicine and tissue engineering. Epigenetic mechanisms, like DNA methylation, contribute to the changes in gene expression in ageing. However there was a lack of sufficient knowledge of the role that differential methylation plays during chondrogenic, osteogenic and tenogenic differentiation from ageing MSCs. This study undertook genome level determination of the effects of DNA methylation on expression in engineered tissues from chronologically aged MSCs. We compiled unique DNA methylation signatures from chondrogenic, osteogenic, and tenogenic engineered tissues derived from young; n = 4 (21.8 years ± 2.4 SD) and old; n = 4 (65.5 years±8.3SD) human MSCs donors using the Illumina HumanMethylation 450 Beadchip arrays and compared these to gene expression by RNA sequencing. Unique and common signatures of global DNA methylation were identified. There were 201, 67 and 32 chondrogenic, osteogenic and tenogenic age-related DE protein-coding genes respectively. Findings inferred the nature of the transcript networks was predominantly for 'cell death and survival', 'cell morphology', and 'cell growth and proliferation'. Further studies are required to validate if this gene expression effect translates to cell events. Alternative splicing (AS) was dysregulated in ageing with 119, 21 and 9 differential splicing events identified in chondrogenic, osteogenic and tenogenic respectively, and enrichment in genes associated principally with metabolic processes. Gene ontology analysis of differentially methylated loci indicated age-related enrichment for all engineered tissue types in 'skeletal system morphogenesis', 'regulation of cell proliferation' and 'regulation of transcription' suggesting that dynamic epigenetic modifications may occur in genes associated with shared and distinct pathways dependent upon engineered tissue type. An altered phenotype in engineered tissues was observed with ageing at numerous levels. These changes represent novel insights into the ageing process, with implications for stem cell therapies in older patients. In addition we have identified a number of tissue-dependant pathways, which warrant further studies.

BACKGROUND:Redox cofactors of NADH/NADPH participate in many cellular metabolic pathways for facilitating the electron transfer from one molecule to another in redox reactions. Transhydrogenase plays an important role in linking catabolism and anabolism, regulating the ratio of NADH/NADPH in cells. The cytoplasmic transhydrogenases could be useful to engineer synthetic biochemical pathways for the production of high-value chemicals and biofuels. METHODOLOGY/PRINCIPAL FINDINGS:A transhydrogenase activity was discovered for a FMN-bound diaphorase (DI) from Geobacillus stearothermophilus under anaerobic conditions. The DI-catalyzed hydride exchange were monitored and characterized between a NAD(P)H and a thio-modified NAD+ analogue. This new function of DI was demonstrated to transfer a hydride from NADPH to NAD+ that was consumed by NAD-specific lactate dehydrogenase and malic dehydrogenase. CONCLUSIONS/SIGNIFICANCE:We discover a novel transhydrogenase activity of a FMN-DI by stabilizing the reduced state of FMNH2 under anaerobic conditions. FMN-DI was demonstrated to catalyze the hydride transfer between NADPH and NAD+. In the future, it may be possible to incorporate this FMN-DI into synthetic enzymatic pathways for balancing NADH generation and NADPH consumption for anaerobic production of biofuels and biochemicals.

This article seeks to relocate the analysis of violence in Palestine within an alternative paradigm that emphasizes long-term processes of global colonization. Beginning from the premise that Palestine is a site of an ongoing settler-colonial project (Zionism) rather than a simple “conflict,” it views contemporary realities as overdetermined by the deep structures that this project has put in place. Using the work of Paul Virilio as a key theoretical touchstone, it explores Palestine’s microcosmic and often prophetic embeddedness in three overlapping colonial modes: exocolonization (the colonization of territories outside one’s own), endocolonization (the colonization of specific populations within the territory under one’s control in the context of permanent or “pure” war), and dromocolonization (the colonization of humanity by techno-scientific acceleration). Examination of these three modes not only sheds light on Zionism’s specific colonial practices (e.g., the exclusion and confinement of Palestinians), but also encourages us to think beyond actor-centered conceptions of politics and consider the impact of processes (e.g., militarization or acceleration) that stretch beyond the control of rational actors. In particular, we see how Palestine has become a laboratory for new forms of warfare and social control whose global implications cannot be overestimated. With this in mind, the article concludes by arguing that an exploration of the challenges and possibilities of decolonization in Palestine can help us think through what global decolonization might mean.

Although the teaching if of African traditional and art music in Ghanaian universities began from independence in 1957, the introduction of local popular music has taken much longer, partly a consequence of imported high-art notion that treated popular music as trivial, ephemeral and low-brow. Although Nkrumah utilised local popular, traditional and arts music in nation building after his overthrow in 1966 his vision was never fully transmitted into the universities where students were only expected to be bi-musical, i.e. familiar with traditional music and art music. The first evidence of a growing Ghanaian academic interest in popular performance studies was the pioneering work of the university lecturers Efua Sutherland, K.N. Bame and Attana Mensah during the 1960s/70s. But this area was not included in the university curriculum until the 1990s, when the University of Ghana changed its position due to several factors. One was the burgeoning local popular music industry (after the music industry decline during the 70s/80s military regimes) and the consequent job opportunities for students. Another was the rise of pop influenced local gospel music from the 1980s that sanctified the guitar and dance-band music. Thirdly there was an interest in Afropop by foreign world music students coming in large numbers after Ghana’s economic liberalisation of the late 1980’s

This article explores the contemporary politics of global violence through an examination of the particular challenges and possibilities facing Palestinians who seek to defend their communities against an ongoing settler-colonial project (Zionism) that is approaching a crisis point. As the colonial dynamic in Israel/Palestine returns to its most elemental level – land, trees, homes – it also continues to be a laboratory for new forms of accelerated violence whose global impact is hard to overestimate. In such a context, Palestinians and international solidarity activists find themselves confronting a quintessential 21st century activist dilemma: how to craft a strategy of what Paul Virilio calls “popular defense” at a time when everyone seems to be implicated in the machinery of global violence? I argue that while this dilemma represents a formidable challenge for Palestinians, it also helps explain why the Palestinian struggle is increasingly able to build bridges with wider struggles for global justice, ecological sustainability, and indigenous rights.

This article explores the contemporary politics of global violence through an examination of the particular challenges and possibilities facing Palestinians who seek to defend their communities against an ongoing settler-colonial project (Zionism) that is approaching a crisis point. As the colonial dynamic in Israel/Palestine returns to its most elemental level – land, trees, homes – it also continues to be a laboratory for new forms of accelerated violence whose global impact is hard to overestimate. In such a context, Palestinians and international solidarity activists find themselves confronting a quintessential 21st century activist dilemma: how to craft a strategy of what Paul Virilio calls “popular defense” at a time when everyone seems to be implicated in the machinery of global violence? I argue that while this dilemma represents a formidable challenge for Palestinians, it also helps explain why the Palestinian struggle is increasingly able to build bridges with wider struggles for global justice, ecological sustainability, and indigenous rights.

BACKGROUNDA varicocele is a meshwork of distended blood vessels in the scrotum, usually left-sided, due to dilatation of the spermatic vein. Although the concept that a varicocele causes male subfertility has been around for more than 50 years now, the mechanisms by which a varicocele would affect fertility have not yet been satisfactorily explained. Neither is there sufficient evidence to explain the mechanisms by which varicocelectomy would restore fertility. Furthermore, it has been questioned whether a causal relation exists at all between the distension of the pampiniform plexus (a network of many small veins found in the human male spermatic cord) and impairment of fertility.OBJECTIVESTo evaluate the effect of varicocele treatment on live birth and pregnancy rate in subfertile couples where the male has a varicocele.METHODSSearchWe searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (12 September 2003 to January 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library Issue 1, 2012), Medline (January 1966 to January 2012), Embase (January 1985 to January 2012), PsycINFO (to Week 1 2012) and reference lists of articles. In addition, we handsearched specialist journals in the field from their first issue until 2012. We also checked cross-references, references from review articles and contacted researchers in the field.Selection criteriaRandomized controlled trials (RCTs) were included if they were relevant to the clinical question posed. If they reported pregnancy rates or live birth rates as an outcome measure, and if they reported data in treated (surgical ligation or radiological embolization of the internal spermatic vein) compared to untreated or placebo groups. Two authors independently screened potentially relevant trials. Any differences of opinion were resolved by consensus (none occurred for this review).Data collection and analysisTen studies met the inclusion criteria for the review. For one study we had only data from a published abstract. All ten studies only included men from couples with subfertility problems; one excluded men with sperm counts less than 5 million per mL and one excluded men with sperm counts less than 2 million per mL, with or without progressive motility of less than 10%. Two trials involving clinical varicoceles included some men with normal semen analysis. Three studies specifically addressed only men with subclinical varicoceles. Studies were excluded from meta-analysis if they made comparisons other than those specified above.MAIN RESULTSThe meta-analysis included 894 men. No studies reported live birth. The combined fixed-effect odds ratio (OR) of the 10 studies for the outcome of pregnancy was 1.47 (95% confidence interval (CI) 1.05 to 2.05, very low quality evidence), favouring the intervention. The number needed to treat for an additional beneficial outcome was 17, suggesting benefit of varicocele treatment over expectant management for pregnancy rate in subfertile couples in whom varicocele in the man was the only abnormal finding. Omission of the studies including men with normal semen analysis and subclinical varicocele, some of which had semen analysis improvement as the primary outcome rather than live birth or pregnancy rate, was the subject of a planned subgroup analysis. The outcome of the subgroup analysis (five studies) also favoured treatment, with a combined OR 2.39 (95% CI 1.56 to 3.66). The number needed to treat for an additional beneficial outcome was 7. The evidence was suggestive rather than conclusive, as the main analysis was subject to fairly high statistical heterogeneity (I2 = 67%) and findings were no longer significant when a random-effects model was used or when analysis was restricted to higher quality studies.AUTHOR' CONCLUSIONSThere is evidence suggesting that treatment of a varicocele in men from couples with otherwise unexplained subfertility may improve a couple's chance of pregnancy. However, findings are inconclusive as the quality of the available evidence is very low and more research is needed with live birth or pregnancy rate as the primary outcome.

Broadband records from ocean-bottom seismometers deployed in the Okinawa trough and the Huatung basin were analyzed to provide seafloor noise characteristics and the detection thresholds for teleseismic body and surface waves. Ambient noise levels on the horizontal components are 10 - 40 dB higher than on the vertical component, with the sensor seated on the surface of the sediment. On the vertical components, infragravity waves are 10 - 30 dB more energetic at the shallower Okinawa trough sites (≤ 2000 m depth) than at the deeper Huatung basin site (~4700 m). From 0.03 to 0.2 Hz, the Huatung basin noise levels are comparable to that of the broadband stations in Taiwan on a quiet day. The microseism peaks (~0.2 - 0.5 Hz) of OBSs reach or exceed the high noise model of continental stations. At regional distances Mw 6.5 is required for recording prominent Rayleigh waves if the source radiation is unfavorable, but 6.2 is sufficient for a favorable focal mecha¬nism. Several tens to over one hundred high-fidelity P, Pdiff and PKP waveforms have been recorded per year by OBSs at high corner frequency of 0.1 Hz with a minimum Mw 5.3 - 6.0. The number of recording drops to less than 5 per year at 1 Hz with Mw ≥ 6.4 and distances less than 90¢X.

BACKGROUNDA varicocele is a meshwork of distended blood vessels in the scrotum, usually left-sided, due to dilatation of the spermatic vein. Although the concept that a varicocele causes male subfertility has been around for more than 50 years now, the mechanisms by which a varicocele would affect fertility have not yet been satisfactorily explained. Neither is there sufficient evidence to explain the mechanisms by which varicocelectomy would restore fertility. Furthermore, it has been questioned whether a causal relation exists at all between the distension of the pampiniform plexus (a network of many small veins found in the human male spermatic cord) and impairment of fertility.OBJECTIVESTo evaluate the effect of varicocele treatment on live birth and pregnancy rate in subfertile couples where the male has a varicocele.METHODSSearchWe searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (12 September 2003 to January 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library Issue 1, 2012), Medline (January 1966 to January 2012), Embase (January 1985 to January 2012), PsycINFO (to Week 1 2012) and reference lists of articles. In addition, we handsearched specialist journals in the field from their first issue until 2012. We also checked cross-references, references from review articles and contacted researchers in the field.Selection criteriaRandomized controlled trials (RCTs) were included if they were relevant to the clinical question posed. If they reported pregnancy rates or live birth rates as an outcome measure, and if they reported data in treated (surgical ligation or radiological embolization of the internal spermatic vein) compared to untreated or placebo groups. Two authors independently screened potentially relevant trials. Any differences of opinion were resolved by consensus (none occurred for this review).Data collection and analysisTen studies met the inclusion criteria for the review. For one study we had only data from a published abstract. All ten studies only included men from couples with subfertility problems; one excluded men with sperm counts less than 5 million per mL and one excluded men with sperm counts less than 2 million per mL, with or without progressive motility of less than 10%. Two trials involving clinical varicoceles included some men with normal semen analysis. Three studies specifically addressed only men with subclinical varicoceles. Studies were excluded from meta-analysis if they made comparisons other than those specified above.MAIN RESULTSThe meta-analysis included 894 men. No studies reported live birth. The combined fixed-effect odds ratio (OR) of the 10 studies for the outcome of pregnancy was 1.47 (95% confidence interval (CI) 1.05 to 2.05, very low quality evidence), favouring the intervention. The number needed to treat for an additional beneficial outcome was 17, suggesting benefit of varicocele treatment over expectant management for pregnancy rate in subfertile couples in whom varicocele in the man was the only abnormal finding. Omission of the studies including men with normal semen analysis and subclinical varicocele, some of which had semen analysis improvement as the primary outcome rather than live birth or pregnancy rate, was the subject of a planned subgroup analysis. The outcome of the subgroup analysis (five studies) also favoured treatment, with a combined OR 2.39 (95% CI 1.56 to 3.66). The number needed to treat for an additional beneficial outcome was 7. The evidence was suggestive rather than conclusive, as the main analysis was subject to fairly high statistical heterogeneity (I2 = 67%) and findings were no longer significant when a random-effects model was used or when analysis was restricted to higher quality studies.AUTHOR' CONCLUSIONSThere is evidence suggesting that treatment of a varicocele in men from couples with otherwise unexplained subfertility may improve a couple's chance of pregnancy. However, findings are inconclusive as the quality of the available evidence is very low and more research is needed with live birth or pregnancy rate as the primary outcome.

Abstract Pulmonary arterial hypertension (PAH, or PH Group 1), a disease of aberrant pulmonary vascular remodeling, causing progressive right heart failure (RHF) due to elevation of pulmonary vascular resistance (PVR). Patient mortality risk stratification guides choice and intensity of pharmacological intervention and is assessed by haemodynamics (especially PVR) as well as noninvasive tools including WHO functional class (FC), 6‐min walk distance (6MWD), and NT‐proBNP levels. Quality of life (QOL) assessment is acknowledged as a central aspect of patient‐centered care, but our study sought to extend QOL's role as an additional noninvasive risk marker that could further refine risk stratification and hence therapeutic choices within a “treatment to target” paradigm (aiming to achieve low‐risk status). This study found that QOL assessment using the PAH‐SYMPACT© physical activity tool provided enhanced, independent mortality risk information, with one unit rise in this score associated with a 41% increase in likelihood risk (odds ratio 1.41, 95% confidence interval: 1.01–1.98 (p

A distinct particle focusing spot occurs in the center of a rotating fluid, presenting an apparent paradox given the presence of particle inertia. It is recognized, however, that the presence of a secondary flow with a radial component drives this particle aggregation. In this study, we expand on the examination of this “Thomson–Einstein’s tea leaf paradox” phenomenon, where we use a combined experimental and computational approach to investigate particle aggregation dynamics. We show that not only the rotational velocity, but also the vessel shape, have a significant influence on a particle’s equilibrium position. We accordingly demonstrate the formation of a single focusing spot in a vessel center, as has been conclusively demonstrated elsewhere, but also the repeatable formation of stable ring-shaped particle arrangements.

PurposeTo investigate the change in axial length (AxL) and choroidal thickness (ChT) in response to continuous and alternating episodes of monocular myopic and hyperopic defocus.MethodsThe right eye of sixteen young adults was exposed to 60 minute episodes of either continuous or alternating myopic and hyperopic defocus (+3 DS & -3 DS) over six separate days, with the left eye optimally corrected for distance. During alternating defocus conditions, the eye was exposed to either 30 or 15 minute cycles of myopic and hyperopic defocus, with the order of defocus reversed in separate sessions. The AxL and ChT of the right eye were measured before, during and after each defocus condition.ResultsSignificant changes in AxL were observed over time, dependent upon the defocus condition (p < 0.0001). In general, AxL exhibited a greater magnitude of change during continuous than alternating defocus conditions. The maximum AxL elongation was +7 ± 7 μm (p = 0.010) in response to continuous hyperopic defocus and the maximum AxL reduction was -8 ± 10 μm of (p = 0.046) in response to continuous myopic defocus. During both 30 and 15 minute cycles of alternating myopic and hyperopic defocus of equal duration, the effect of opposing blur sessions cancelled each other and the AxL was near baseline levels following the final defocus session (mean change from baseline across all alternating defocus conditions was +2 ± 10 μm, p > 0.05). Similar, but smaller magnitude, changes were observed for ChT.ConclusionsThe human eye appears capable of temporal averaging of visual cues from alternating myopic and hyperopic defocus. In the short term, this integration appears to be a cancellation of the effects of the preceding defocus condition of opposite sign.

Although considerable evidence supports that misfolded prion protein (PrPSc) is the principal component of "prions", underpinning both transmissibility and neurotoxicity, clear consensus around a number of fundamental aspects of pathogenesis has not been achieved, including the time of appearance of neurotoxic species during disease evolution. Utilizing a recently reported electrophysiology paradigm, we assessed the acute synaptotoxicity of ex vivo PrPSc prepared as crude homogenates from brains of M1000 infected wild-type mice (cM1000) harvested at time-points representing 30%, 50%, 70% and 100% of the terminal stage of disease (TSD). Acute synaptotoxicity was assessed by measuring the capacity of cM1000 to impair hippocampal CA1 region long-term potentiation (LTP) and post-tetanic potentiation (PTP) in explant slices. Of particular note, cM1000 from 30% of the TSD was able to cause significant impairment of LTP and PTP, with the induced failure of LTP increasing over subsequent time-points while the capacity of cM1000 to induce PTP failure appeared maximal even at this early stage of disease progression. Evidence that the synaptotoxicity directly related to PrP species was demonstrated by the significant rescue of LTP dysfunction at each time-point through immuno-depletion of >50% of total PrP species from cM1000 preparations. Moreover, similar to our previous observations at the terminal stage of M1000 prion disease, size fractionation chromatography revealed that capacity for acute synpatotoxicity correlated with predominance of oligomeric PrP species in infected brains across all time points, with the profile appearing maximised by 50% of the TSD. Using enhanced sensitivity western blotting, modestly proteinase K (PK)-resistant PrPSc was detectable at very low levels in cM1000 at 30% of the TSD, becoming robustly detectable by 70% of the TSD at which time substantial levels of highly PK-resistant PrPSc was also evident. Further illustrating the biochemical evolution of acutely synaptotoxic species the synaptotoxicity of cM1000 from 30%, 50% and 70% of the TSD, but not at 100% TSD, was abolished by digestion of immuno-captured PrP species with mild PK treatment (5μg/ml for an hour at 37°C), demonstrating that the predominant synaptotoxic PrPSc species up to and including 70% of the TSD were proteinase-sensitive. Overall, these findings in combination with our previous assessments of transmitting prions support that synaptotoxic and infectious M1000 PrPSc species co-exist from at least 30% of the TSD, simultaneously increasing thereafter, albeit with eventual plateauing of transmitting conformers.

Although misfolding of normal prion protein (PrPC) into abnormal conformers (PrPSc) is critical for prion disease pathogenesis our current understanding of the underlying molecular pathophysiology is rudimentary. Exploiting an electrophysiology paradigm, herein we report that at least modestly proteinase K (PK)-resistant PrPSc (PrPres) species are acutely synaptotoxic. Brief exposure to ex vivo PrPSc from two mouse-adapted prion strains (M1000 and MU02) prepared as crude brain homogenates (cM1000 and cMU02) and cell lysates from chronically M1000-infected RK13 cells (MoRK13-Inf) caused significant impairment of hippocampal CA1 region long-term potentiation (LTP), with the LTP disruption approximating that reported during the evolution of murine prion disease. Proof of PrPSc (especially PrPres) species as the synaptotoxic agent was demonstrated by: significant rescue of LTP following selective immuno-depletion of total PrP from cM1000 (dM1000); modestly PK-treated cM1000 (PK+M1000) retaining full synaptotoxicity; and restoration of the LTP impairment when employing reconstituted, PK-eluted, immuno-precipitated M1000 preparations (PK+IP-M1000). Additional detailed electrophysiological analyses exemplified by impairment of post-tetanic potentiation (PTP) suggest possible heightened pre-synaptic vulnerability to the acute synaptotoxicity. This dysfunction correlated with cumulative insufficiency of replenishment of the readily releasable pool (RRP) of vesicles during repeated high-frequency stimulation utilised for induction of LTP. Broadly comparable results with LTP and PTP impairment were obtained utilizing hippocampal slices from PrPC knockout (PrPo/o) mice, with cM1000 serial dilution assessments revealing similar sensitivity of PrPo/o and wild type (WT) slices. Size fractionation chromatography demonstrated that synaptotoxic PrP correlated with PK-resistant species >100kDa, consistent with multimeric PrPSc, with levels of these species >6 ng/ml appearing sufficient to induce synaptic dysfunction. Biochemical analyses of hippocampal slices manifesting acute synaptotoxicity demonstrated reduced levels of multiple key synaptic proteins, albeit with noteworthy differences in PrPo/o slices, while such changes were absent in hippocampi demonstrating rescued LTP through treatment with dM1000. Our findings offer important new mechanistic insights into the synaptic impairment underlying prion disease, enhancing prospects for development of targeted effective therapies.

There seems to be general agreement on the importance of challenge for effective development on the athlete pathway. What seems less coherent, however, are ideas on how much, when and how this challenge should be used. Reflecting our own experience as applied practitioners and our ongoing research, we offer a perspective on this work from a practitioner stance. The literature suggests that differences between levels of adult achievement relate more to what performers bring to the challenges than what they experience. Therefore, it is essential that young athletes have the opportunity to develop psycho-behavioural and coping skills, and have adequate social support, to ensure that adversity is interpreted as a positive growth experience. A periodized and progressive set of challenge, preceded with specific skill development, would seem to offer the best pathway to success. The importance of preparing athletes for challenges, supporting them through the experience, and then encouraging positive evaluation and reflection is key to successful outcome. Finally, we offer some suggestions, structures and systems which can be used to support the skill-based approach promoted.

This article aims to understand Paul’s argument about ‘seeds’ and ‘seed’ in Galatians 3:16 — first, by discerning which text of Genesis lies behind it; and secondly, by using recent grammatical work on ‘seed’ in Hebrew to discern whether the Hebrew is collective or singular. The article concludes that Paul was using Genesis 22:18, which speaks of an individual offspring, and that he properly applied it to Jesus as a Messianic text.

This article examines the possibility that the Hebrew wayyiqtol verb form itself, without a previous perfect, may denote what in Western languages would be expressed by a pluperfect tense, and attempts to articulate how we might discern it in a given passage, and the communicative effect of such a usage. The article concludes that there is an unmarked pluperfect usage of the wayyiqtol verb form; and that it may be detected when one of three conditions is met. Application of these results demonstrates that this usage is not present in 1 Samuel 14:24, while it is present in Genesis 2:19.