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This study evaluated the long-term clinical outcomes of single-visit root canal treatments with apical enlargement on patients with necrotic pulp tissue retrospectively. A total of 137 teeth with necrotic pulp tissue which underwent single-visit root canal treatments were included. The root canals were shaped up until the apical constriction, which was determined by an apex locator. The outcomes were evaluated by two independent and calibrated endodontists clinically and radiographically. Teeth were dichotomized into healed (PAI≤2, no signs or symptoms) and nonhealed (PAI>2, with/without signs or symptoms) groups. Each patients’ preoperative PAI and lesion size were recorded to evaluate the preoperative periapical status as well as several other prognostic factors. Statistical analyses were performed (p=0.05) on ninety teeth. The mean observation time was 60 months. Out of ninety teeth, 87 (96.7%) were healed and 3 (3.3%) were nonhealed. No correlations were found between the prognostic factors and the outcomes (p>0.05). Cohen’s kappa and Gwet’s agreement coefficient scores between the preoperative PAI scores and preoperative lesion sizes showed good agreements, with values of 0.834 and 0.898, respectively. Apical enlargement is a viable treatment option for single-visit root canal treatments.

Asylum seekers and refugees continue to face serious obstacles in their efforts to access asylum. Some of these obstacles are inherent to irregular migration, including dangerous border crossings and the risk of exploitation. Yet, refugees also face state-made obstacles in the form of sophisticated migration control measures. As a result, refugees are routinely denied access to asylum as developed states close their borders in the hope of shifting the flow of asylum seekers to neighboring countries. Restrictive migration control policies are today the primary, some might say only, response of the developed world to rising numbers of asylum seekers and refugees. This has produced a distorted refugee regime both in Europe and globally — a regime fundamentally based on the principle of deterrence rather than human rights protection. While the vast majority of European states still formally laud the international legal framework to protect refugees, most of these countries simultaneously do everything in their power to exclude those fleeing international protection and offer only a minimalist engagement to assist those countries hosting the largest number of refugees. By deterring or blocking onward movement for refugees, an even larger burden is placed upon these host countries. Today, 86 percent of the world's refugees reside in a low- or middle-income country, against 70 percent 20 years ago (Edwards 2016; UNHCR 2015, 15). The humanitarian consequences of this approach are becoming increasingly clear. Last year more than 5,000 migrants and refugees were registered dead or missing in the Mediterranean (IOM 2016). A record number, this makes the Mediterranean account for more than two-thirds of all registered migrant fatalities worldwide (IOM 2016). Many more asylum seekers are subjected to various forms of violence and abuse during the migratory process as a result of their inherently vulnerable and clandestine position. As the industry facilitating irregular migration grows, unfortunately so too do attempts to exploit migrants and refugees by smugglers, criminal networks, governments, or members of local communities (Gammeltoft-Hansen and Nyberg Sørensen 2013). The “deterrence paradigm” can be understood as a particular instantiation of the global refugee protection regime. It shows how deterrence policies have come to dominate responses to asylum seekers arriving in developed states, and how such policies have continued to develop in response to changes in migration patterns as well as legal impositions. The dominance of the deterrence paradigm also explains the continued reliance on deterrence as a response to the most recent “crisis,” despite continued calls from scholars and civil society for a more protection-oriented and sustainable response. The paper argues that the current “crisis,” more than a crisis in terms of refugee numbers and global protection capacity, should be seen a crisis in terms of the institutionalized responses so far pursued by states. Deterrence policies are being increasingly challenged, both by developments in international law and by less wealthy states left to shoulder the vast majority of the world's refugees. At the same time, recent events suggest that deterrence policies may not remain an effective tool to prevent secondary movement of refugees in the face of rising global protection needs, while deterrence involves increasing direct and indirect costs for the states involved. The present situation may thus be characterized as, or at least approaching, a period of paradigm crisis, and we may be seeing the beginning of the end for deterrence as a dominant policy paradigm in regard to global refugee policy. In its place, a range of more or less developed alternative policy frameworks are currently competing, though so far none of them appear to have gained sufficient traction to initiate an actual paradigm shift in terms of global refugee policy. Nonetheless, recognizing this as a case of possible paradigm change may help guide and structure this process. In particular, any successful new policy approach would have to address the fundamental challenges facing the old paradigm. The paper proceeds in four parts. Firstly, it traces the rise of the deterrence paradigm following the end of the Cold War and the demise of ideologically driven refugee protection on the part of states in the Global North. The past 30 years have seen the introduction and dynamic development of manifold deterrence policies to stymie the irregular arrival of asylum seekers and migrants. This array of measures is explored in the second part of the paper through a typology of five current practices that today make up “normal policymaking” within the deterrence regime. Third, the paper argues that the current paradigm is under threat, facing challenges to its legality from within refugee and human rights law; to its sustainability due to the increasing unhappiness of refugee-hosting states with current levels of “burden-sharing”; and to its effectiveness as direct and indirect costs of maintaining the regime mount. Finally, the paper puts forward three core principles that can lay the groundwork in the event of a paradigm shift: respect for international refugee law; meaningful burden-sharing; and a broader notion of refugee protection that encompasses livelihoods and increased preparedness in anticipation of future refugee flows.

Chemical synthesis typically relies on reactions that generate complexity through elaboration of simple starting materials. Less common are deconstructive strategies toward complexity—particularly those involving carbon-carbon bond scission. Here, we introduce one such transformation: the hydrodealkenylative cleavage of C(sp³)–C(sp²) bonds, conducted below room temperature, using ozone, an iron salt, and a hydrogen atom donor. These reactions are performed in nonanhydrous solvents and open to the air; reach completion within 30 minutes; and deliver their products in high yields, even on decagram scales. We have used this broadly functionality tolerant transformation to produce desirable synthetic intermediates, many of which are optically active, from abundantly available terpenes and terpenoid-derived precursors. We have also applied it in the formal total syntheses of complex molecules.

Free-flowing rivers (FFRs) support diverse, complex and dynamic ecosystems globally, providing important societal and economic services. Infrastructure development threatens the ecosystem processes, biodiversity and services that these rivers support. Here we assess the connectivity status of 12 million kilometres of rivers globally and identify those that remain free-flowing in their entire length. Only 37 per cent of rivers longer than 1,000 kilometres remain free-flowing over their entire length and 23 per cent flow uninterrupted to the ocean. Very long FFRs are largely restricted to remote regions of the Arctic and of the Amazon and Congo basins. In densely populated areas only few very long rivers remain free-flowing, such as the Irrawaddy and Salween. Dams and reservoirs and their up- and downstream propagation of fragmentation and flow regulation are the leading contributors to the loss of river connectivity. By applying a new method to quantify riverine connectivity and map FFRs, we provide a foundation for concerted global and national strategies to maintain or restore them. A comprehensive assessment of the world’s rivers and their connectivity shows that only 37 per cent of rivers longer than 1,000 kilometres remain free-flowing over their entire length.

Cases of foodborne disease caused by Salmonella are frequently associated with the consumption of minimally processed produce. Bacterial cell surface components are known to be important for the attachment of bacterial pathogens to fresh produce. The role of these extracellular structures in Salmonella attachment to plant cell walls has not been investigated in detail. We investigated the role of flagella, fimbriae and cellulose on the attachment of Salmonella Typhimurium ATCC 14028 and a range of isogenic deletion mutants (ΔfliC fljB, ΔbcsA, ΔcsgA, ΔcsgA bcsA and ΔcsgD) to bacterial cellulose (BC)-based plant cell wall models [BC-Pectin (BCP), BC-Xyloglucan (BCX) and BC-Pectin-Xyloglucan (BCPX)] after growth at different temperatures (28°C and 37°C). We found that all three cell surface components were produced at 28°C but only the flagella was produced at 37°C. Flagella appeared to be most important for attachment (reduction of up to 1.5 log CFU/cm2) although both cellulose and fimbriae also aided in attachment. The csgD deletion mutant, which lacks both cellulose and fimbriae, showed significantly higher attachment as compared to wild type cells at 37°C. This may be due to the increased expression of flagella-related genes which are also indirectly regulated by the csgD gene. Our study suggests that bacterial attachment to plant cell walls is a complex process involving many factors. Although flagella, cellulose and fimbriae all aid in attachment, these structures are not the only mechanism as no strain was completely defective in its attachment.

Lethal recessive alleles cause pre- or postnatal death in homozygous affected individuals, reducing fertility. Especially in small size domestic and wild populations, those alleles might be exposed by inbreeding, caused by matings between related parents that inherited the same recessive lethal allele from a common ancestor. In this study we report five relatively common (up to 13.4% carrier frequency) recessive lethal haplotypes in two commercial pig populations. The lethal haplotypes have a large effect on carrier-by-carrier matings, decreasing litter sizes by 15.1 to 21.6%. The causal mutations are of different type including two splice-site variants (affecting POLR1B and TADA2A genes), one frameshift (URB1), and one missense (PNKP) variant, resulting in a complete loss-of-function of these essential genes. The recessive lethal alleles affect up to 2.9% of the litters within a single population and are responsible for the death of 0.52% of the total population of embryos. Moreover, we provide compelling evidence that the identified embryonic lethal alleles contribute to the observed heterosis effect for fertility (i.e. larger litters in crossbred offspring). Together, this work marks specific recessive lethal variation describing its functional consequences at the molecular, phenotypic, and population level, providing a unique model to better understand fertility and heterosis in livestock.

At initiation of X chromosome inactivation (XCI), Xist is monoallelically upregulated from the future inactive X (Xi) chromosome, overcoming repression by its antisense transcript Tsix . Xist recruits various chromatin remodelers, amongst them SPEN, which are involved in silencing of X-linked genes in cis and establishment of the Xi. Here, we show that SPEN plays an important role in initiation of XCI. Spen null female mouse embryonic stem cells (ESCs) are defective in Xist upregulation upon differentiation. We find that Xist -mediated SPEN recruitment to the Xi chromosome happens very early in XCI, and that SPEN-mediated silencing of the Tsix promoter is required for Xist upregulation. Accordingly, failed Xist upregulation in Spen −/− ESCs can be rescued by concomitant removal of Tsix . These findings indicate that SPEN is not only required for the establishment of the Xi, but is also crucial in initiation of the XCI process. SPEN is a key player in initiation of X chromosome inactivation. Here, the authors show that SPEN is required for Xist-mediated silencing of its own antisense regulator Tsix.

With low liquidus temperatures, low raw material costs, and non-toxicity, Sn-Bi low-temperature solders are promising candidates for the replacement of the currently widely-used lead-free solders in situations in which process temperatures have to be reduced. Electrical resistivity is one of the most important properties of solder alloys, as one of their primary functions is to conduct electrons between the connected components. The electrical resistivity of an alloy of a given composition at a specific temperature and pressure is affected by the microstructure and the crystal structure of the phases present. For Sn-Bi solders, the solubility of Bi in Sn is highly temperature-sensitive and increases from 3 wt.% at room temperature to 21 wt.% at 139°C, the eutectic temperature of the Sn-Bi system. As the temperature increases within that interval, Bi will dissolve in Sn, while it will precipitate as the temperature decreases. The resulting significant changes in the overall microstructure and the lattice parameters of the Sn phase can be expected to affect the electrical resistivity. In this study, the electrical resistivity of hypo-eutectic Sn-37wt.%Bi and near-eutectic Sn-57wt.%Bi alloys was measured as a function of temperature and the temperature coefficient of resistance (TCR) calculated. It was found that the electrical resistivity increases linearly with increasing temperature up to 70°C, while above 80°C, a deviation from the linear relationship was observed. This deviation is attributed to the rapid dissolution of Bi in Sn at 80°C and above.

The different rates of thermal expansion of the many materials that make up an electronic assembly combined with temperature fluctuations are the driver of the thermal fatigue failure of solder joints. A characteristic of the Sn-Bi system, which provided the basis for many of the low process temperature solder alloys that the electronics industry is now adopting, is the very temperature-sensitive solubility of Bi and Sn in the other phase. In this study, in situ synchrotron powder x-ray diffraction was used to characterize the temperature dependence of the lattice parameters of the βSn and Bi phases in Sn-57wt%Bi and Sn-37wt%Bi. The effects of temperature and solute were separated by comparing with the data from pure βSn and pure Bi and verified using density functional theory calculations. Furthermore, the coefficients of thermal expansion of βSn and Bi during heating were also derived to reveal the thermal expansion behavior.