Overdose deaths involving prescription opioids killed more than 17,000 Americans in 2017, marking a five-fold increase since 1999. High prescribing rates of opioid analgesics have been a substantial contributor to prescription opioid misuse, dependence, overdose and heroin use. There was recognition approximately ten years ago that opioid prescribing patterns were contributing to this startling increase in negative opioid-related outcomes, and federal actions, including Medicare reimbursement reform and regulatory actions, were initiated to restrict opioid prescribing. The current manuscript is a description of those actions, the effect of those actions on opioid prescribing and related patient outcomes. We also describe our proposal of methods of expanding these efforts as an important piece to further reduce opioid-related misuse, dependence, and overdose death.

Both sequential Monte Carlo (SMC) methods (a.k.a. ‘particle filters’) and sequential Markov chain Monte Carlo (sequential MCMC) methods constitute classes of algorithms which can be used to approximate expectations with respect to (a sequence of) probability distributions and their normalising constants. While SMC methods sample particles conditionally independently at each time step, sequential MCMC methods sample particles according to a Markov chain Monte Carlo (MCMC) kernel. Introduced over twenty years ago in [6], sequential MCMC methods have attracted renewed interest recently as they empirically outperform SMC methods in some applications. We establish an $\mathbb{L}_r$ -inequality (which implies a strong law of large numbers) and a central limit theorem for sequential MCMC methods and provide conditions under which errors can be controlled uniformly in time. In the context of state-space models, we also provide conditions under which sequential MCMC methods can indeed outperform standard SMC methods in terms of asymptotic variance of the corresponding Monte Carlo estimators.

The current study describes the results obtained from clinical examination of over 4700 suckling piglets from 19 individual herds in Germany. In this cohort the prevalence of inflammation and necrosis in the tails, ears, claw coronary bands, heels and teats was determined using a pre-defined scoring system. Results show that already in the 1st days of life, piglets were affected by inflammation and necrosis of the heels (80%), claw coronary bands (50%) and tail base (20%). The praevalences of these alterations in piglets were influenced by genetics (P <0.001) and age, decreasing gradually in the 2nd week of life (P <0.001). Moreover, a correlation between tail length after tail docking and the prevalence of tail necrosis (P⩽0.04) was found. Tail and ear biting as a behavioural trait was not detected during this study. The early onset, appearance and multiple locations of clinical signs of inflammation and the positive correlation with the genetic background of the piglets may suggest an impairment of the innate immune system by infectious and non-infectious agents. This is in contrast to previously described behavioural abnormalities seen in fattening pigs. Considering the obvious reduction of animal welfare due to the described lesions, there is a need to create awareness among pig farmers and to understand the multifactorial causality involved in this inflammation and necrosis syndrome in piglets.

The transformation of global capitalism, labor, and class relations in our own day is having a marked effect on how we study those subjects historically. Yet, as happens repeatedly in our historical discipline, insights gained from the juxtaposition and recognition of deep structural affinities between the present and the past also carry the risk of a distorted mirror effect. What questions we carry to the past and what lessons we, in turn, extract from it must be handled with care. As couriers between worlds of time as well as space, our work as historians inevitably reflects the ignorance as well as intelligence attending the message (as well as the messenger) of the given moment. With these caveats in mind, I want to explore the link between today's global crisis in worker welfare—perhaps most commonly summoned up by the twinned terms “neoliberalism” and the “precariat”—and a new historical preoccupation with coerced laborers of the past. With due deference to the aims of this collection, I will concentrate on the connection between the coolie question, as it developed in the nineteenth and early twentieth centuries, with the plight (and possible strategies) of low-wage global workers today.

ESA's Gaia space astrometry mission is performing an all-sky survey of stellar objects. At the beginning of the nominal mission in July 2014, an operation scheme was adopted that enabled Gaia to routinely acquire observations of all stars brighter than the original limit of G~6, i.e. the naked-eye stars. We present the current status and extent of those observations.

Prebiotic oligosaccharides, including galacto-oligosaccharides (GOS), are used in infant formula to mimic human milk oligosaccharides, which are known to have an important role in the development of the intestinal microbiota and the immune system in neonates. The maturation of the intestines in piglets closely resembles that of human neonates and infants. Hence, a neonatal piglet model was used to study the multi-faceted effect of dietary GOS in early life. Naturally farrowed piglets were separated from the mother sow 24–48 h postpartum and received a milk replacer with or without the addition of GOS for 3 or 26 d, whereafter several indicators of intestinal colonisation and maturation were measured. Dietary GOS was readily fermented in the colon, leading to a decreased pH, an increase in butyric acid in caecum digesta and an increase in lactobacilli and bifidobacteria numbers at day 26. Histomorphological changes were observed in the intestines of piglets fed a GOS diet for 3 or 26 d. In turn, differences in the intestinal disaccharidase activity were observed between control and GOS-fed piglets. The mRNA expression of various tight junction proteins was up-regulated in the intestines of piglet fed a GOS diet and was not accompanied by an increase in protein expression. GOS also increased defensin porcine β-defensin-2 in the colon and secretory IgA levels in saliva. In conclusion, by applying a neonatal piglet model, it could be demonstrated that a GOS-supplemented milk replacer promotes the balance of the developing intestinal microbiota, improves the intestinal architecture and seems to stimulate the intestinal defence mechanism.

Kalahari Group sediments accumulated in the Kalahari basin, which started forming during the breakup of Gondwana in the early Cretaceous. These sediments cover an extensive part of southern Africa and form a low-relief landscape. Current models assume that the Kalahari Group accumulated throughout the entire Cenozoic. However, chronology has been restricted to early–middle Cenozoic biostratigraphic correlations and to OSL dating of only the past ~ 300 ka. We present a new chronological framework that reveals a dynamic nature of sedimentation in the southern Kalahari. Cosmogenic burial ages obtained from a 55 m section of Kalahari Group sediments from the Mamatwan Mine, southern Kalahari, indicate that the majority of deposition at this location occurred rapidly at 1–1.2 Ma. This Pleistocene sequence overlies the Archaean basement, forming a significant hiatus that permits the possibility of many Phanerozoic cycles of deposition and erosion no longer preserved in the sedimentary record. Our data also establish the existence of a shallow early–middle Pleistocene water body that persisted for > 450 ka prior to this rapid period of deposition. Evidence from neighboring archeological excavations in southern Africa suggests an association of high-density hominin occupation with this water body.

Vegetable production systems are often characterized by excessive nitrogen (N) fertilization and the incorporation of large amounts of post-harvest crop residues. This makes them particularly prone to ammonia (NH3) and nitrous oxide (N2O) emissions. Yet, urgently needed management strategies that can reduce these harmful emissions are missing, because underlying processes are not fully understood. The present study therefore focuses on the effects of residue placement on NH3 and N2O emissions. For this, cauliflower leaf residues (286 kg N/ha) were either applied as surface mulch (mulch) or mixed with the topsoil (mix) and in situ NH3 and N2O emissions were investigated. The experiment took place on a sandy soil in Northeastern Germany during summer 2012. Residue application created a high peak in N2O emissions during the first 2 weeks, irrespective of residue placement. There was no significant difference in the emission sums over the experimental period (65 days) between the mix (5·8 ± 0·68 kg N2O-N/ha) and the mulch (9·7 ± 1·53 kg N2O-N/ha) treatment. This was also the case for NH3 emissions, which exhibited a lower initial peak followed by a prolonged decline. Measured emission sums were 4·1 ± 0·33 (mix) and 5·1 ± 0·73 (mulch) kg NH3-N/ha. It was concluded that substantial NH3 and N2O emissions can occur after high input of available organic carbon and N even in a coarse-textured soil with low water-holding capacity. Other than expected, surface-application does not enhance NH3 emissions at the expense of N2O emissions compared with residue mixing into the soil, at least under the conditions of the present study.

The Dead Sea fault (DSF) is one of the most active plate boundaries in the world. Understanding the Quaternary history and sediments of the DSF requires investigation into the Neogene development of this plate boundary. DSF lateral motion preceded significant extension and rift morphology by ~10 Ma. Sediments of the Sedom Formation, dated here between 5.0 ± 0.5 Ma and 6.2−2.1 +inf Ma, yielded extremely low 10Be concentrations and 26Al is absent. These reflect the antiquity of the sediments, deposited in the Sedom Lagoon, which evolved in a subdued landscape and was connected to the Mediterranean Sea. The base of the overlying Amora Formation, deposited in the terminal Amora Lake which developed under increasing relief that promoted escarpment incision, was dated at 3.3−0.8 +0.9 Ma. Burial ages of fluvial sediments within caves (3.4 ± 0.2 Ma and 3.6 ± 0.4 Ma) represent the timing of initial incision. Initial DSF topography coincides with the earliest Red Sea MORB's and the East Anatolian fault initiation. These suggest a change in the relative Arabian–African plate motion. This change introduced the rifting component to the DSF followed by a significant subsidence, margin uplift, and a reorganization of relief and drainage pattern in the region resulting in the topographic framework observed today.