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Males and females in sexually dimorphic species show differences in their physiology and behaviour due to differences in energetic investment into reproduction and soma. This means that the two sexes may show different patterns of parasitism at different times of the year. In this study, we evaluate the abundance of fecal eggs and larvae of 5 parasite types (Strongyles, Nematodirus spp., Marshallagia marshalli., Protostrongylus spp. lungworms, and Eimeria spp.) in relation to season and sex in Rocky Mountain bighorn sheep (Ovis canadensis). We use fecal egg counts (FEC) as a proxy for infection intensity. Parasite FECs differed between male and female bighorn sheep and varied with season. We found pronounced fluctuations in fecal egg counts of various parasite species in males and females across different seasons and reproductive stages. Strongyle counts were significantly higher during late gestation and lactation/summer, and particularly pronounced in males. Nematodirus counts were highest during late gestation in females and during the rut in males. Marshallagia counts peaked during late gestation in females and during the rut in males. Protostrongylus spp. lungworm counts were highest during late gestation in females and in males during lactation/summer and the rut. Eimeria oocyst counts varied across seasons, with higher counts in males during the rut and in females during winter and late gestation. Additionally, significant differences in Strongyle counts were observed between coursing and tending rams, with tending rams exhibiting higher counts. We discuss why the sexes might differ in FECs and suggest that differences between FECs of the parasites across seasons may be due to different life cycles and cold tolerance of the parasites themselves.

Abstract Background The past few decades have seen rapid advancements in exoskeleton technology, with a considerable shift towards applications involving users with gait pathologies. Commercial devices from ReWalk, Ekso Bionics, and Indego, mainly designed for rehabilitation purposes, have inspired the development of many research platforms aimed at extending capabilities for use as safe and effective personal mobility devices. The 2016 Cybathlon featured an impressive demonstration of exoskeletons designed to enable mobility for individuals with spinal cord injury, however, not a single team completed every task and only two completed the stairs. Major improvements were showcased at the 2020 Cybathlon, with seven of the nine teams completing a similar set of tasks. Team IHMC built upon its silver-medal success from 2016 with an upgraded device, Quix. Methods Quix features several notable improvements including an additional powered degree of freedom for hip ab/adduction to laterally shift the device and reduce user effort while walking, custom-tailored cuffs and soft goods based on 3D body scans to optimize user comfort, and a streamlined testing pipeline for online tuning of gait parameters. Results Team IHMC finished in fourth place behind the teams from EPFL and Angel Robotics. Although we suffered from a considerably slower flat-ground walking speed, our pilot reported marked improvements in overall effort, comfort, and ease-of-use compared to our previous device. Conclusions Clear progress in exoskeleton development has been exhibited since the inaugural Cybathlon, with tasks involving rough terrain, stairs, and ramps now posing little threat to most of the competitors. As a result, the layout of the powered exoskeleton course will likely undergo significant modifications to further push the devices towards suitability for personal everyday use. The current tasks do not address the issue of donning and doffing, nor do they simulate a scenario similar to maneuvering a kitchen to prepare a meal, for example. An additional limitation that may be more difficult to test in a competition setting is the required upper-body effort to manipulate the device in an effective manner.

BackgroundLiver transplantation (LT) is considered a therapeutic option for unresectable perihilar cholangiocarcinoma (PHC) within defined criteria. It remains uncertain whether patients can safely receive adjuvant chemotherapy after LT.MethodsWe performed a prospective, multi-center, randomized, non-blinded two-arm trial (pro-duct001). Patients after LT for unresectable PHC within defined criteria were randomized to adjuvant gemcitabine (LT-Gem group) and LT alone (LT alone group). The primary objective was to investigate if adjuvant chemotherapy is feasible in ≥ 85% of patients after LT. The primary endpoint was the percentage of patients completing the 24 weeks course of adjuvant chemotherapy. Secondary endpoints included overall survival (OS) and disease-free (DFS), and complication rates.ResultsTwelve patients underwent LT for PHC, of which six (50%) were eligible for randomization (LT-Gem: three patients, LT alone: three patients). Two out of three patients discontinued adjuvant chemotherapy after LT due to intolerance. The study was prematurely terminated due to slow enrollment. One patient with PHC had underlying primary sclerosing cholangitis (PSC). Tumor-free margins could be achieved in all patients. In both the LT-Gem and the LT alone group, the cumulative 1-, 3-, and 5-year OS and DFS rates were 100%, 100%, 67%, and 100%, 67% and 67%, respectively.ConclusionsThis prospective, multi-center study was prematurely terminated due to slow enrollment and a statement on the defined endpoints cannot be made. Nevertheless, long-term survival data are consistent with available retrospective data and confirm defined criteria for LT. Since more evidence of LT per se in unresectable PHC is urgently needed, a prospective, non-randomized follow-up study (pro-duct002) has since been launched.

Abstract Phenological shifts associated with directional changes in climate, resulting in earlier spring activities, have been documented in several animal species. However, the extent to which species respond to overall climate change versus local climate variation is rarely studied. In addition, climate data are usually averaged over large spatial scales, even though local heterogeneity in habitats may be high, and species might be more susceptible to changes in local rather than global climate conditions. In this study, we examined the effects of spatiotemporal climate variation and climate change on the phenology of a hibernating mountain rodent, the Columbian ground squirrel (Urocitellus columbianus). Over 28 years of research (1992–2019), we studied the relationship between the microclimatic conditions experienced by adult and juvenile ground squirrels from four neighboring meadows, and their dates of emergence from hibernation. We used a microclimate model to calculate microclimate variables (local snow depth, soil temperature, air temperature, wind speed, and humidity) at an hourly scale, a 5‐m spatial resolution, and at animal height on the study sites over 28 years. Emergence dates varied with age and sex, among years, as well as among and within meadows, with some areas averaging up to 10 days earlier emergence dates from hibernation than others. While emergence dates tended to be delayed throughout the study period, long‐term temporal changes and interannual variability in emergence dates differed among meadows and depended on individual age and sex. Dates of hibernation emergence were correlated with local climate variables considered either during hibernation or during the preceding summer. Ground squirrels emerged earlier in years or at locations when/where snow melted earlier (years: all individuals excluding 2‐year‐old males, locations: yearlings and older females), and when the previous summer was less windy (≥3‐year‐old individuals) and more humid (2‐year‐old males). Two‐year‐old male ground squirrels also emerged later in locations where snow depth during winter was higher. Using a microclimate model allowed realistic predictions of phenological responses to climate, highlighting its potential for research on animal responses to abiotic change.

Sexual segregation is a common phenomenon among animals, particularly dimorphic ones. Although widely addressed, the reasons and consequences of sexual segregation are still an important topic in need of better understanding. In this study, we mainly evaluate the diet composition and feeding behaviour of animals, which are related to the use of different habitats by the sexes, a special case of sexual segregation also termed habitat segregation. Sexually size dimorphic males and females often have different energetic and nutritional needs and, thus, different diets. We collected fresh faecal samples from wild Iberian red deer (Cervus elaphus L.) in Portugal. Samples were analysed in terms of diet composition and quality. As expected, both sexes differed in their diet composition, with males eating more arboreous species than females, but this difference was affected by sampling periods. Diet composition of both sexes had the biggest differences (and the lowest overlap) in spring, which corresponds to the end of gestation and beginning of birth. These differences might be a consequence of the sexual body size dimorphism characteristic of this species, as well as of different needs due to different reproductive costs. No differences regarding the quality of the excreted diet were observed. Our results may help to understand some patterns of sexual segregation observed in this red deer population. However, besides foraging ecology, other factors may also be contributing to sexual segregation in this Mediterranean population of red deer, and further studies focusing on sexual differences regarding feeding behaviour and digestibility are needed.

Next-generation wireless communications systems are anticipated to utilize the vast amount of available spectrum in the millimeter-wave and sub-terahertz bands above $\mathrm {100~ \text {G} \text {Hz} }$ to meet the ever-increasing demand for higher data rates. However, the analog-to-digital converter (ADC) power consumption is expected to be a major bottleneck if conventional system designs are employed at these frequencies. Instead, shifting the ADC resolution from the amplitude domain to the time domain by employing 1-bit quantization and temporal oversampling w.r.t. the Nyquist rate is expected to be more energy-efficient. Hence, we consider a system employing 1-bit quantization and temporal oversampling at the receiver, which operates on a wideband line-of-sight channel. We present a practical transceiver design for a zero-crossing modulation waveform, which combines faster-than-Nyquist signaling and runlength-limited (RLL) transmit sequences. To this aim, we derive four fixed-length finite-state machine RLL encoders enabling efficient transmit signal construction and soft-demapping at the receiver. Moreover, we propose a soft-output equalizer, which approximates maximum a posteriori RLL symbol detection. We evaluate the system performance in terms of peak-to-average-power ratio, coded block error rate, and a lower bound on the spectral efficiency (SE) w.r.t. a fractional power containment bandwidth. Our numerical results show that SEs of up to 4 bit/s/Hz are achievable with the presented transceiver design.

The next generation of mobile communication system will allow a plethora of new services and use cases. By offering support for high throughput connections, low latency response and massive number of connections, the fifth generation of the mobile network will trigger applications unseen in any other network. However, one important application scenario is not being properly addressed by the players responsible for the mobile networks' standardization, that is the remote and rural areas network. This scenario requires large cells with high throughput, flexibility to opportunistically exploit free bands below 1 GHz and spectrum agility to change the operational frequency when an incumbent is detected. Incipient actions are being considered for the Release 17 but based on the new radio specification as starting point. The limitations imposed by orthogonal waveforms in the physical layers hinder the exploitation of vacant TV channels in rural and remote areas. 5G-RANGE, a Brazil-Europe bilateral cooperation project, aims at conceiving, implementing and deploying an innovative mobile network, designed to provide reliable and cost-effective connection in these regions. This network can be seamlessly integrated with the other 5G scenarios, closing the connectivity gap between the urban, rural and remote areas. Hence, 5G-RANGE network is an interesting complementary solution for beyond 5G standards. This paper presents the major achievements of the 5G-RANGE project, from the design of the physical, medium access control and network layers, to the field demonstrations. The paper also covers the business models that can be used to make the deployment of this technology a reality.

Abstract Background As a research scientist, my work tends to focus on scientific investigations. Our group occasionally makes discoveries or has a successful demonstration, and sometimes we can even repeatedly demonstrate something working on the hardware. This mode of operation works for research, but not for competitions. In the past few years, I have participated in two international robotics competitions, the DARPA Robotics Challenge (DRC) and the Cybathlon; the research and development process for these competitions is significantly different from our typical research work. This commentary discusses our experience preparing for the Cybathlon, and contrasts it with our experience with the DRC. Main body The human in the loop for the Cybathlon was the biggest differentiator between the DRC and the Cybathlon. Having the human at the center of the competition not only changed the way we developed, but changed how we viewed the impact of our work. For the DRC, a physics based dynamic simulation was a powerful, and invaluable, tool for not only the algorithm developers, but the robot operator as well. For the Cybathlon, simulation was of little use because the all of closed-loop control was performed by the pilot. In the software development cycle for the Cybathlon, the push was to just come up with something that works and “lock it down” and do not change it, so that the pilot could train with a given set of motions that would not change and make up for any deficiencies with his own abilities. The Cybathlon was more of an athletic challenge for the human who was assisted by technology. The DRC was the opposite, it was a robotics challenge assisted by a human. This commentary focuses on describing the Florida Institute for Human and Machine Cognition’s (IHMC) experience leading up to and at the Cybathlon, with some comparisons to the DRC experience. Conclusion The Cybathlon was a very worthwhile experience me, my team, and of course our pilot. Knowing that our development could improve the quality of life and health for a group of people was very motivating and rewarding. Engineering competitions accelerate development, engage the public, and in the case of the Cybathlon, increase public awareness of issues for people with disabilities. The Cybathlon also revealed that the powered exoskeleton technology is still nascent in its ability to be a viable alternative to the wheelchair. But with continued developments toward the 2020 Cybathlon, we hope the capabilities of these devices can offer will be significantly improved.

Within many species, males are often more heavily parasitised than females. Several hypotheses have been proposed to explain this phenomenon, including immunocompetence handicaps, sexual size dimorphism and behavioural differences. Here we set out to test the latter two hypotheses and make inferences about the former by assessing patterns of ectoparasitism across various life-history stages in a population of North American red squirrels (Tamiasciurus hudsonicus). We also conducted an ectoparasite removal experiment to investigate the effects of ectoparasites on male body condition. We found that males were more intensely parasitized than females, but only during the mating period. There was no difference in ectoparasite intensity between male and female juveniles at birth or at emergence, suggesting that ectoparasites do not exploit male red squirrels for longer-range natal dispersal. Male red squirrels in our population were slightly heavier than females, however we did not find any evidence that this dimorphism drives male-biased ectoparasitism. Finally, we could not detect an effect of ectoparasite removal on male body mass. Our results lend support to the hypothesis that ectoparasites exploit their male hosts for transmission and that male red squirrels are important for the transmission dynamics of ectoparasites in this population; however, the mechanisms (i.e., immunocompetence, testosterone) are not known.

Background. Arterial ex situ back-table perfusion (BP) reportedly reduces ischemic-type biliary lesion after liver transplantation. We aimed to verify these findings in a prospective investigation. Methods. Our prospective, randomized, controlled, multicenter study involved livers retrieved from patients in 2 German regions, and compared the outcomes of standard aortic perfusion to those of aortic perfusion combined with arterial ex situ BP. The primary endpoint was the incidence of ischemic-type biliary lesions over a follow-up of 2 years after liver transplantation, whereas secondary endpoints included 2-year graft survival, initial graft damage as reflected by transaminase levels, and functional biliary parameters at 6 months after transplantation. Results. A total of 75 livers preserved via standard aortic perfusion and 75 preserved via standard aortic perfusion plus arterial BP were treated using a standardized protocol. The incidence of clinically apparent biliary lesions after liver transplantation (n = 9 for both groups; P = 0.947), the 2-year graft survival rate (standard aortic perfusion, 74%; standard aortic perfusion plus arterial BP, 68%; P = 0.34), and incidence of initial graft injury did not differ between the 2 perfusion modes. Although 33 of the 77 patients with cholangiography workups exhibited injured bile ducts, only 10 had clinical symptoms. Conclusions. Contrary to previous findings, the present study indicated that additional ex situ BP did not prevent ischemic-type biliary lesions or ischemia-reperfusion injury after liver transplantation. Moreover, there was considerable discrepancy between cholangiography findings regarding bile duct changes and clinically apparent cholangiopathy after transplantation, which should be considered when assessing ischemic-type biliary lesions.

Background. Acute liver failure (ALF) is a rare but potentially life-threatening condition and liver transplantation (LTX) remains frequently the only effective therapy. Nevertheless, some patients recover without LTX but the individual indication for or against LTX remains difficult.Aim. To evaluate maximal liver function capacity (LiMAx) for predicting the prognosis of ALF.Material and methods. Clinic data of 12 patients was retrospectively analyzed to compare the different liver function test results with the patients’ clinical outcome. Patients were assessed by the LiMAx test, a non-invasive breath test determining cytochrome P450 1A2 capacity using intravenous 13C-methacetin. Statistical analysis compared patients with spontaneous recovery versus non-recovery (LTX or death).Results. Twelve patients (6 male, 6 female; 49 [11–72] years) with viral hepatitis (n = 2), toxic liver injury (n = 3), or cryptogenic liver failure (n = 7) were analyzed. Seven patients fully recovered from ALF and were discharged without LTX. Three patients died and two underwent LTX. The King’s College Criteria (KCC) was fulfilled in only one out of five patients without recovery. The LiMAx was 19 ± 19 (16–62) for non-recovery vs. 94 ± 119 (39–378) μg/kg/h for recovery (P = 0.018). In contrast, all biochemical parameters [bilirubin (P = 0.106), creatinine (P = 0.343), AST (P = 0.53), ALT (P = 0.876) and INR (P = 0.876) were statistically indistinct. Also the Model for End-Stage Liver Disease (MELD) score did not show a difference [35 ± 4.3 (29–40) vs. 30 ± 11.5 (6–40); P = 0.27].Conclusions. Maximal liver function capacity determined by LiMAx test is severely impaired in patients with ALF. The LiMAx test might be effective in predicting the individual prognosis and the need for LTX in ALF.

We studied the putative significance of angiotensin I-converting enzyme (ACE) in colorectal cancer (CRC) biology. Local expression of ACE was investigated by quantitative reverse transcription- polymerase chain reaction and by immunohistochemistry in CRCs and adenomas. ACE insertion (I)/deletion (D) polymorphism was studied in 141 CRC patients and 189 controls. ACE mRNA was upregulated in CRCs compared to corresponding nonlesional tissues (2.5-fold; P = .009). ACE protein was more commonly expressed in adenomas [17 (81 %)] and cancer epithelial cells [22 (100%)] than in corresponding non-neoplastic crypt and surface epithelium [2 (10%) and 2 (9%), respectively]. Thirty-seven CRC patients (26%) carried II genotype, 69 (49%) carried ID genotype, 35 (25%) carried DD genotype. The distribution of the genotypes did not differ from that of controls. Female CRC patients more commonly carried the ID genotype and less frequently the II and DD genotypes compared with male patients (P = .033). Men heterozygous or homozygous for the D-allele had larger tumors compared to carriers of the II genotype (P < .01). Women homozygous for the D-allele lived longer than carriers of the ID and II genotypes. Our study shows that ACE is differentially expressed in CRCs and that gene polymorphism is associated with gender-specific differences in primary tumor size and patient survival.

OBJECTIVE: Aim of this study was to evaluate the association between preoperative health-related quality of life (HRQoL) and mortality in a cohort of elderly patients (>65 years) with gastrointestinal, gynecological and genitourinary carcinomas. DESIGN: Prospective cohort pilot study. SETTING: Tertiary university hospital in Germany. PATIENTS: Between June 2008 and July 2010 and after ethical committee approval and written informed consent, 126 patients scheduled for onco-surgery were included. Prior to surgery as well as 3 and 12 months postoperatively all participants completed the EORTC-QLQ-C30 questionnaire (measuring self-reported health-related quality of life). Additionally, demographic and clinical data including the Mini Mental State Examination (MMSE) were collected. Surgery and anesthesia were conducted according to the standard operating procedures. Primary endpoint was the cumulative mortality rate over 12 months after one year. Changes in Quality of life were considered as secondary outcome. RESULTS: Mortality after one year was 28%. In univariable and multivariable logistic regression analysis baseline HRQoL self-reported cognitive function (OR per point: 0.98; CI 95% 0.96-0.99; p = 0.024) and higher symptom burden for appetite loss (per point: OR 1.02; CI 95% 1.00-1.03; p = 0.014) were predictive for long-term mortality. Additionally the MMSE as an objective measure of cognitive impairment (per point: OR 0.69; CI 95% 0.51-0.96; p = 0.026) as well as severity of surgery (OR 0.31; CI 95% 0.11-0.93; p = 0.036) were predictive for long-term mortality. Global health status 12 months after surgery was comparable to the baseline levels in survivors despite moderate impairments in other domains. CONCLUSION: This study showed that objective and self-reported cognitive functioning together with appetite loss were prognostic for mortality in elderly cancer patients. In addition, impaired cognitive dysfunction and severity of surgery were predictive for one-year mortality whereas in this selected population scheduled for surgery age, gender, cancer site and metastases were not.

Cellular therapies require methods for noninvasive visualization of transplanted cells. Micron-sized iron oxide particles (MPIOs) generate a strong contrast in magnetic resonance imaging (MRI) and are therefore ideally suited as an intracellular contrast agent to image cells under clinical conditions. However, MPIOs were previously not applicable for clinical use. Here, we present the development and evaluation of silica-based micron-sized iron oxide particles (sMPIOs) with a functionalizable particle surface. Particles with magnetite content of >40% were composed using the sol-gel process. The particle surfaces were covered with COOH groups. Fluorescein, poly-l-lysine (PLL), and streptavidin (SA) were covalently attached. Monodisperse sMPIOs had an average size of 1.18 μm and an iron content of about 1.0 pg Fe/particle. Particle uptake, toxicity, and imaging studies were performed using HuH7 cells and human and rat hepatocytes. sMPIOs enabled rapid cellular labeling within 4 h of incubation; PLL-modified particles had the highest uptake. In T2*-weighted 3.0 T MRI, the detection threshold in agarose was 1,000 labeled cells, whereas in T1-weighted LAVA sequences, at least 10,000 cells were necessary to induce sufficient contrast. Labeling was stable and had no adverse effects on labeled cells. Silica is a biocompatible material that has been approved for clinical use. sMPIOs could therefore be suitable for future clinical applications in cellular MRI, especially in settings that require strong cellular contrast. Moreover, the particle surface provides the opportunity to create multifunctional particles for targeted delivery and diagnostics.

In order to evaluate potential reproductive costs associated with parasitism, we experimentally removed ectoparasites from reproductive female North American red squirrels (Tamiasciurus hudsonicus). Body mass and overwinter survival of mothers, days to juvenile emergence, juvenile survival from birth to emergence, and body mass of juveniles at emergence were all compared to those of untreated (control) animals. Ectoparasite removal did not affect the body mass of mothers throughout the lactation period and overwinter survival of mothers did not differ between treatments and controls. Likewise, there was no effect of treatment on the number of days to juvenile emergence. However, treated mothers raised offspring that were significantly heavier (11%) than controls at emergence. Juveniles from treated mothers were also 24% more likely to survive from birth to emergence. Our results indicate that ectoparasites impose costs on the reproductive success of female red squirrels and that ectoparasites have the potential to influence red squirrel life-histories and population dynamics.

Background and aimsPancreatic cancer risk is increased in Lynch syndrome (LS) patients with mismatch repair gene defects predisposing to colonic and extracolonic cancers with microsatellite instability (MSI). However, the frequency of MSI pancreatic cancers has never been ascertained in consecutive, unselected clinical series, and their contribution to the sporadic and inherited burden of pancreatic cancer remains to be established. Aims of the study were to determine the prevalence of MSI in surgically resected pancreatic cancers in a multicentric, retrospective study, and to assess the occurrence of pancreatic cancer in LS.MethodsMS-status was screened by a panel of 5 mononucleotide repeats (Bat26, Bat25, NR-21, NR-24 and NR-27) in 338 consecutive pancreatic ductal adenocarcinoma (PDAC), resected at two Italian and one German referral centres. The personal history of pancreatic cancer was assessed in an independent set of 58 probands with LS and in 138 first degree relatives who had cancers.ResultsOnly one PDAC (0.3%) showed MSI. This was a medullary type cancer, with hMLH1-deficiency, and no identified germ-line mutation but methylation of hMLH1. Pancreatic cancer occurred in 5 (2.5%) LS patients. Histological sampling was available for 2 cases, revealing PDAC in one case and an ampullary cancer in the other one.ConclusionsMSI prevalence is negligible in sporadic, resected PDAC. Differently, the prevalence of pancreatic cancer is 2.5% in LS patients, and cancers other than PDAC may be encountered in this setting. Surveillance for pancreatic cancer should be advised in LS mutation carriers at referral centers.

It has been shown that certain chemokine receptor polymorphisms may correspond to certain complications after organ transplantation. Ischemic-type biliary lesion (ITBL) encounters for major morbidity and mortality in liver transplant recipients. So far, the exact cause for ITBL remains unclear. Certain risk factors for the development of ITBL like donor age and cold ischemic time are well described. In a previous study, a 32-nucleotide deletion of the chemokine receptor-5Δ32 (CCR-5Δ32) was strongly associated with the incidence of ITBL in adult liver transplantation. This study re-evaluates the association of CCR-5Δ32 gene polymorphism and the incidence of ITBL. 169 patients were included into this retrospective analysis. 134 patients were homozygous for wild-type CCR-5, 33 patients heterozygous, and 2 patients were homozygous for CCR-5Δ32 mutation. There were no major differences in donor or recipients demographics. No association was found between CCR-5Δ32 mutation and the development of ITBL. We conclude that CCR-5Δ32 is no risk factor for the development of ITBL in our patient cohort.