There is currently a heightened need for transparency in pharmaceutical sectors. The inclusion of real-world (RW) evidence, in addition to clinical trial evidence, in decision-making processes, was an important step forward toward a more inclusive established value proposition. This advance has introduced new transparency challenges. Increasing transparency is a critical step toward accelerating improvement in type, quality, and access to data, regardless of whether these originate from clinical trials or from RW studies. However, so far, advances in transparency have been relatively restricted to clinical trials, and there remains a lack of similar expectations or standards of transparency concerning the generation and reporting of RW data. This perspective paper aims to highlight the need for transparency concerning RW studies, data, and evidence across health care sectors, to identify areas for improvement, and provide concrete recommendations and practices for the future. Specific issues are discussed from different stakeholder perspectives, culminating in recommended actions, from individual stakeholder perspectives, for improved RW study, data, and evidence transparency. Furthermore, a list of potential guidelines for consideration by stakeholders is proposed. While recommendations from different stakeholder perspectives are made, true transparency in the processes involved in the generation, reporting, and use of RW evidence will require a concerted effort from all stakeholders across health care sectors.

Economic margins on pig farms are small, and changing slaughter weights may increase farm profitability. However, one can question if the optimal slaughter weight is the same for each sex. On three farms, crossbred pigs (n = 1128) were used to determine the effect of sex and slaughter weight on performance, carcass quality and gross margin per pig place per year. On each farm, an equal number of entire males (EMs), barrows (BAs), immunocastrates (IC) and gilts (GIs) were housed separately in group pens. Pens were randomly divided into three categories of different slaughter weights: 105, 117 and 130 kg BW. In BA, the high average daily feed intake (ADFI) and the lower capacity to gain muscle led to a higher feed conversion ratio (FCR) and lower lean meat percentage in comparison to EM and IC. In all sexes, ADFI and FCR increased with an increasing slaughter weight but the effect of slaughter weight on carcass quality varied between sexes. In BA and GI, slaughter weight had no effect on carcass quality, but in EM and IC, carcass quality improved at higher slaughter weights. Gross margin per pig place per year was calculated as gross margin per pig × barn turnover per year, taking into account fixed costs per round, feed costs and output price per pig. The slaughter weight that gained the highest gross margin per year differed between sexes. Slaughtering BA and GI at 130 kg BW, compared to 105 or 117 kg BW, decreased the gross margin per pig place per year due to the lower margin per pig and barn turnover at higher weights. In IC and EM, no difference in gross margin per pig place per year could be demonstrated between slaughtering at 105, 117 or 130 kg BW. In IC, the increasing gross margin per pig with increasing slaughter weights counteracted with the lower barn turnover. In EM, gross margin per pig did not differ between slaughter weights, but the effect of barn turnover was too small to demonstrate significant differences between slaughter weights on gross margin per pig place per year. In conclusion, slaughter weight has an impact on profitability in BA and GI: they should not be slaughtered at 130 kg BW but at lower weights, but no effect could be demonstrated in EM and IC.

Genetic evaluation of Piétrain sires in Flanders occurs under standardized conditions, on test stations with fixed dam breeds, standardized diets and uniform management practices. As environmental conditions vary on commercial farms and differ from the test stations, this study aimed at understanding to what extent the sire, the dam breed and the interaction between both affects the translation of breeding values to practice. Dams of two commercial breeds were inseminated with semen from one of five different sires selected for contrasting breeding values (daily gain, feed conversion ratio and carcass quality). For each sire by dam breed combination, six pen replicates (with three gilts and three barrows per pen) were evaluated for growth performance from 9 weeks of age (20 kg) to slaughter (110 kg), and for carcass and meat quality. In our experimental setup, both sire and dam breed affected growth, carcass and meat quality traits. No significant sire×dam breed interactions on performance could be detected. Though a tendency for interaction on average daily feed intake between 20 and 110 kg (P=0.087), and on pork colour (lightness) (P=0.093) was present. In general, offspring of all tested sires behaved similarly in both dam breeds, indicating that estimated breeding values for Piétrain sires determined in one dam breed are representative in other dam breeds as well.

During growth, pigs convert plant protein into animal protein. The major part of the ingested protein is excreted via manure, with potential nitrogen (N) losses to the environment. To limit N losses and increase sustainability of pork production, the efficiency of protein conversion should be maximized. The aim of this paper is to critically evaluate diet and management strategies linked with N efficiency. Besides nutrition, we discuss three management strategies observed in science and in practice to be linked with improved N efficiency: genetic selection, castration and slaughter weight. Because diet has a marked effect on eventual N losses, it must also be taken into account when evaluating management strategies. A reductionist approach, such as feeding the same diet across all management treatments, may overestimate the effect of a management strategy and eventually lead to incorrect conclusions. The amount of excreted N depends on the amount of ingested N, the amount of absorbed N, the amino acid (AA) balance in the diet and the animal’s N and AA requirements. Daily multiphase feeding adapted to the individual animal’s AA needs is likely to be the most N efficient. For animals housed in groups, phase feeding is necessary. When combined with periods of temporary AA restriction, N efficiency can be further improved. Specific AA consumption must be balanced by applying the ideal protein concept. With better knowledge of the requirements of individual animals and the commercial availability of certain AAs, the total dietary CP level can be lowered within limits. Further research is needed on the minimal CP level that allows maximal performance. For this end a useful parameter may be the ratio of standardized ileal digestible (SID) lysine : apparent total tract digestible CP level. By combining optimal nutrition and management, a whole body N efficiency approaching 60% may be achievable in the near future.

We consider a specific accumulation event that occurred in January 2002 in western Dronning Maud Land, Antarctica. Snow samples were obtained a few days after accumulation. We combine meteorological analyses and isotopic modelling to describe the isotopic composition of moisture during transport. Backward trajectories were calculated, based on European Centre for Medium-Range Weather Forecasts operational archive data so that the history of the air parcels transporting water vapour to the accumulation site could be reconstructed. This trajectory study showed that the air masses were not (super)saturated along most of the transport path, which is in contrast with assumptions in Lagrangian fractionation models and probably true for most precipitation events in Antarctica. The modelled fractionation along the trajectories was too limited to explain the measured isotopic content of the snow. It is shown that the observed isotopic composition of precipitation resulted from fractionation of initially more depleted water. This lower initial isotopic composition of water vapour might result from atmospheric mixing with more depleted air along the trajectory or from earlier condensation cycles, not captured by the trajectories. This is in accordance with isotope fields resulting from general circulation models, indicating a gradient in isotopic composition from the Equator to Antarctica.

Persistent katabatic winds form widely distributed localized areas of near-zero net surface accumulation on the East Antarctic ice sheet (EAIS) plateau. These areas have been called 'glaze' surfaces due to their polished appearance. They are typically 2-200 km2 in area and are found on leeward slopes of ice-sheet undulations and megadunes. Adjacent, leeward high-accumulation regions (isolated dunes) are generally smaller and do not compensate for the local low in surface mass balance (SMB). We use a combination of satellite remote sensing and field-gathered datasets to map the extent of wind glaze in the EAIS above 1500 m elevation. Mapping criteria are derived from distinctive surface and subsurface characteristics of glaze areas resulting from many years of intense annual temperature cycling without significant burial. Our results show that 11.2 ± 1.7%, or 950 ± 143 × 103km2, of the EAIS above 1500 m is wind glaze. Studies of SMB interpolate values across glaze regions, leading to overestimates of net mass input. Using our derived wind-glaze extent, we estimate this excess in three recent models of Antarctic SMB at 46-82 Gt. The lowest-input model appears to best match the mean in regions of extensive wind glaze.

Short-term ice-dynamical processes at Greenland’s Jakobshavn and Kangerdlugssuaq glaciers were studied using a 3 day time series of synthetic aperture radar data acquired during the 2011 European Remote-sensing Satellite-2 (ERS-2) 3 day repeat campaign together with modelled meteorological parameters. The time series spans the period March–July 2011 and captures the first ~30% of the summer melting season. In both study areas, we observe velocity fluctuations at the lower ~10 km of the glacier. At Jakobshavn Isbræ, where our dataset covers the first part of the seasonal calving-front retreat, we identify ten calving episodes, with a mean calving-front area loss of 1.29 ± 0.4 km2. Significant glacier speed-up was observed in the near-terminus area following all calving episodes. We identify changes in calving-front geometry as the dominant control on velocity fluctuations on both glaciers, apart from a <15% early-summer speed-up at Kangerdlugssuaq Glacier during a period of calving-front advance, which we attribute to enhanced surface melt-induced basal lubrication. Our 3 day velocity maps show new spatial characteristics of the ice melange flow variability in the Jakobshavn and Kangerdlugssuaq fjord systems, which are primarily controlled by calving-front dynamics and fjord geometry.

This study evaluates the impact of a recent upgrade in the physics package of the regional atmospheric climate model RACMO2 on the simulated surface mass balance (SMB) of the Antarctic ice sheet. The modelled SMB increases, in particular over the grounded ice sheet of East Antarctica (+44 Gt a–1), with a small change in West Antarctica. This mainly results from an increase in precipitation, which is explained by changes in the cloud microphysics, including a new parameterization for ice cloud supersaturation, and changes in large-scale circulation patterns, which alter topographically forced precipitation. The spatial changes in SMB are evaluated using 3234 in situ SMB observations and ice-balance velocities, and the temporal variability using GRACE satellite retrievals. The in situ observations and balance velocities show a clear improvement of the spatial representation of the SMB in the interior of East Antarctica, which has become considerably wetter. No improvements are seen for West Antarctica and the coastal regions. A comparison of model SMB temporal variability with GRACE satellite retrievals shows no significant change in performance.

Understanding the climate response of the Antarctic Peninsula ice sheet is vital for accurate predictions of sea-level rise. However, since climate models are typically too coarse to capture spatial variability in local scale meteorological processes, our ability to study specific sectors has been limited by the local fidelity of such models and the (often sparse) availability of observations. We show that a high-resolution (5.5 km × 5.5 km) version of a regional climate model (RACMO2.3) can reproduce observed interannual variability in the Larsen B embayment sufficiently to enable its use in investigating long-term changes in this sector. Using the model, together with automatic weather station data, we confirm previous findings that the year of the Larsen B ice shelf collapse (2001/02) was a strong melt year, but discover that total annual melt production was in fact ~30% lower than 2 years prior. While the year before collapse exhibited the lowest melting and highest snowfall during 1980–2014, the ice shelf was likely pre-conditioned for collapse by a series of strong melt years in the 1990s. Melt energy has since returned to pre-1990s levels, which likely explains the lack of further significant collapse in the region (e.g. of SCAR Inlet).

C band backscatter parameters contain information about the upper snowpack/firn in the dry snow zone. The wide incidence angle diversity of the Advanced Scatterometer (ASCAT) gives unprecedented characterisation of backscatter anisotropy, revealing the backscatter response to climatic forcing. The A (isotropic component) and M2 (bi-sinusoidal azimuth anisotropy) parameters are investigated here, in conjunction with data from atmospheric and snowpack models, to identify the backscatter response to surface forcing parameters (wind speed and persistence, precipitation, surface temperature, density and grain size). The long-term mean A parameter is successfully recreated with a regression using these drivers, indicating strong links between the A parameter and precipitation on long timescales. While the ASCAT time series is too short to determine which factors drive observed trends, factors influencing the seasonal and short timescale variability are revealed. On these timescales, A strongly responds to the propagation of surface temperature cycles/anomalies downward through the firn, via direct modulation of the dielectric constant. The influence of precipitation on A is small at shorter timescales. The M2 parameter is controlled by wind speed and persistence, through modification of monodirectionally-aligned surface roughness. This variability indicates that throughout much of coastal Antarctica, a microwave ‘snapshot’ is generally not representative of longer-term conditions.

Societal pressure to ban surgical castration of male piglets is rising due to animal welfare concerns, thus other methods to prevent boar taint need to be explored. Genetic selection against boar taint appears to be a long-term sustainable alternative. However, as boar taint is linked to reproductive hormones, it is important to consider possible negative side effects such as delayed sexual maturity or changes in behaviour. We reported earlier that the melanocortin-4 receptor (MC4R) marker can be used to reduce boar taint levels in fat of boars. The objective of this study was to evaluate whether MC4R marker-assisted selection for lower boar taint prevalence affects plasma levels of boar taint compounds and testosterone; sexual maturity; behaviour; skin lesions; and lameness in boars and gilts. Using an intervention study with a 2×2 design, 264 boars and gilts differing on position 893 of the MC4R gene (AA v. GG) were compared. The MC4R polymorphism did not affect the plasma concentration of either androstenone or testosterone at different time points, whereas the concentration of skatole was significantly lower (P=0.003) and the concentration of indole tended to be lower (P=0.074) in GG compared with AA boars. A higher percentage of gilts of the GG genotype were in puberty at slaughter age compared with AA gilts (P<0.001). The age of the boars at sexual maturity (as indicated by the first positive preputial smear test) did not differ between AA and GG boars. In contrast, weight of GG boars at sexual maturity tended to be lower (P=0.065). During the period from 6 weeks of age to slaughter, boars and gilts of the GG genotype showed more playing behaviour (P=0.015) and less passive and feeding behaviour (P=0.003). They showed more skin lesions on their back and caudal area (P=0.022), and tended to show more skin lesions on their head and anterior area (P=0.093) compared with AA animals. In conclusion, the polymorphism in the MC4R gene can be used as a marker without negative effects on reproduction characteristics in boars and gilts. Genetic selection towards a lower prevalence of boar taint will lead to more active pigs with more skin lesions. Management strategies may therefore be necessary to reduce skin lesions in the selected animals.

Mounted police horses have to cope with challenging, unpredictable situations when on duty and it is essential to gain insight into how these horses handle stress to warrant their welfare. The aim of the study was to evaluate physiological and behavioral responses of 12 (six experienced and six inexperienced) police horses during police training. Horses were evaluated during four test settings at three time points over a 7-week period: outdoor track test, street track test, indoor arena test and smoke machine test. Heart rate (HR; beats/min), HR variability (HRV; root means square of successive differences; ms), behavior score (BS; scores 0 to 5) and standard police performance score (PPS; scores 1 to 0) were obtained per test. All data were statistically evaluated using a linear mixed model (Akaike's Information criterium; t > 2.00) or logistic regression (P < 0.05). HR of horses was increased at indoor arena test (98 ± 26) and smoke machine test (107 ± 25) compared with outdoor track (80 ± 12, t = 2.83 and t = 3.91, respectively) and street track tests (81 ± 14, t = 2.48 and t = 3.52, respectively). HRV of horses at the indoor arena test (42.4 ± 50.2) was significantly lower compared with street track test (85.7 ± 94.3 and t = 2.78). BS did not show significant differences between tests and HR of horses was not always correlated with the observed moderate behavioral responses. HR, HRV, PPS and BS did not differ between repetition of tests and there were no significant differences in any of the four tests between experienced and inexperienced horses. No habituation occurred during the test weeks, and experience as a police horse does not seem to be a key factor in how these horses handle stress. All horses showed only modest behavioral responses, and HR may provide complimentary information for individual evaluation and welfare assessment of these horses. Overall, little evidence of stress was observed during these police training tests. As three of these tests (excluding the indoor arena test) reflect normal police work, it is suggested that this kind of police work is not significantly stressful for horses and will have no negative impact on the horse's welfare.

Extended abstract of a paper presented at Microscopy and Microanalysis 2011 in Nashville, Tennessee, USA, August 7–August 11, 2011.

Icy grain mantles are commonly observed through infrared spectroscopy toward dense clouds, cloud cores, protostellar envelopes and protoplanetary disks. Up to 80% of the available oxygen, carbon and nitrogen are found in such ices; the most common ice constituents – H2O, CO2 and CO – are second in abundance only to H2 in many star forming regions. In addition to being a molecular reservoir, ice chemistry is responsible for much of the chemical evolution from H2O to complex, prebiotic molecules. Combining the exisiting ISO, Spitzer, VLT and Keck ice data results in a large sample of ice sources (~80) that span all stages of star formation and a large range of protostellar luminosities (<0.1–105 L⊙). Here we summarize the different techniques that have been applied to mine this ice data set on information on typical ice compositions in different environments and what this implies about how ices form and evolve during star and planet formation. The focus is on how to maximize the use of empirical constraints from ice observations, followed by the application of information from experiments and models. This strategy is used to identify ice bands and to constrain which ices form early during cloud formation, which form later in the prestellar core and which require protostellar heat and/or UV radiation to form. The utility of statistical tests, survival analysis and ice maps is highlighted; the latter directly reveals that the prestellar ice formation takes place in two phases, associated with H2O and CO ice formation, respectively, and that most protostellar ice variation can be explained by differences in the prestellar CO ice formation stage. Finally, special attention is paid to the difficulty of observing complex ices directly and how gas observations, experiments and models help in constraining this ice chemistry stage.

We compared the prevalence of human and animal methicillin-resistant Staphylococcus aureus (MRSA) at pig farms in The Netherlands, and related this to individual and farm-level characteristics. More than half of the farms investigated (28/50) had MRSA in pigs or stable dust and about one third (15/50) of person(s) were identified as MRSA carriers. Human carriage was found only on farms with MRSA-positive pigs or dust. MRSA strains in human samples were the same spa-type as found in pigs and all were not typable by pulsed-field gel electrophoresis (NT-MRSA). Multivariate analyses showed that risk factors for human MRSA carriage were: working in pig stables (OR 40, 95% CI 8–209) and the presence of sows and finishing pigs (OR 9, 95% CI 3–30). Veterinary sample collectors sampling the pigs showed transient MRSA carriage only during the day of the farm visit. Working in pig stables with MRSA-positive pigs poses a high risk for acquiring MRSA, increasingly so when contact with live pigs is more intensive or long lasting.

Summary

Background and objective: Anaesthesiologists need parameters that measure the depth of anaesthesia. In the context of this need, the present study investigated in rats how two variables from the electroencephalogram, the burst suppression ratio and effective correlation dimension correlated with a measure of anaesthetic depth as measured in the strength of a noxious withdrawal reflex. Methods: Eight rats were exposed to different inspiratory concentrations of sevoflurane, each rat in two separate experiments. In the first experiment, spontaneously breathing animals could move freely and no painful stimuli were applied. In the second experiment, in mechanically ventilated restrained anaesthetized rats, the withdrawal reflex was measured every 80 s. In both experiments the electroencephalogram was continuously recorded. The concentration in the effector compartment was estimated using a first order two compartment model. Correlation dimension was computed following the Grassberger/Procaccia/Takens approach with optimized parameter settings to achieve maximum sensitivity to anaesthetic drug effects and enable real-time computation. The Hill, equation was fitted to the data, describing the effect as a function of sevoflurane concentration. Results: Good correlations of Depth of Anaesthesia with correlation dimension as well as burst suppression ratio were established in both types of experiments. Arousal by noxious stimuli decreased burst suppression ratio and increased correlation dimension. The effective sevoflurane concentration associated with 50% of the maximum effect (C50) was higher in experiment II (stimulation) than in experiment I (no stimulation): i.e. for correlation dimension 2.18% vs. 0.60% and for burst suppression ratio 3.07% vs. 1.73%. The slope factors were: γCD = 4.15 vs. γCD = 1.73 and γBSR = 5.2 vs. γBSR = 5.4. Correlation dimension and burst suppression ratio both correlated with the strength of the withdrawal reflex with correlation coefficients of 0.46 and 0.66 respectively (P < 0.001). Conclusions: Both correlation dimension and burst suppression ratio are related to anaesthetic depth and are affected by noxious stimuli. The relationship between anaesthetic depth and burst suppression ratio is confirmed and the potential of correlation dimension is demonstrated.

In 2002, in The Netherlands a national study of gastroenteritis outbreaks was performed. Epidemiological information was collected by the Public Health Services (PHS) and the Food Inspection Services (FIS) using standardized questionnaires. Stool samples were collected for diagnostic testing. For foodborne outbreaks, food samples were taken. In total, 281 gastroenteritis outbreaks were included, mainly from nursing homes and homes for the elderly (57%), restaurants (11%), hospitals (9%) and day-care centres (7%). Direct person-to-person spread was the predominant transmission route in all settings (overall 78%), except for restaurant outbreaks where food was suspected in almost 90% (overall in 21% of outbreaks). The most common pathogen was norovirus (54%), followed by Salmonella spp. (4%), rotavirus group A (2%), Campylobacter spp. (1%) and only incidentally others. In conclusion, most outbreaks were reported from health and residential institutions, with norovirus as the dominant agent. Control should aim at reducing person-to-person spread. In foodborne outbreaks norovirus was common, due to contamination of food by food handlers. Salmonella, as the second foodborne pathogen, was mainly associated with raw shell eggs. These results stress the continuous need for food safety education, complementary to governmental regulation.

During the past two decades, accelerator mass spectrometry (AMS) has allowed major developments in many areas of geosciences and archaeology. In the near future, AMS should realize a similar potential in the field of biomedical research, leading ultimately to clinical applications. For such applications, the required instrument differs significantly from that presently used in the field of 14C dating. Whereas the needed accuracy and sensitivity is more than an order of magnitude less demanding than that for present state-of-the-art 14C instrumentation, the widespread acceptance of 14C AMS in biomedical research will require AMS spectrometers that are small, simple to operate and capable of handling CO2 samples. In order to satisfy these demands, HVEE has developed a compact 14C AMS spectrometer dedicated to biomedical research. The instrument consists of a compact accelerator with a footprint of 2.25 × 1.25 m and an ion source that features direct CO2 acceptance and optimal user friendliness. Having previously described the layout and design of the accelerator, we here discuss progress on the accelerator and present the design and first results of the CO2 ion source.

Abstract A rare case of a symptomatic venous anomaly of the parotid gland is described in a 14-year-old female patient who presented with Turkey Wattle sign. A definitive diagnosis of this disorder requires venographic studies. Surgical treatment was successful, with a follow-up of four years.