Echinococcus multilocularis in red foxes (Vulpes vulpes) of the Italian Alpine region: is there a focus of autochthonous transmission?

Alveolar echinococcosis, caused by the metacestode of Echinococcus multilocularis, is a zoonosis with a wider distribution area than described in the past. Fox populations living in the Alpine regions of Italy had been considered free from this parasite until 2002, when two infected foxes (Vulpes vulpes) were detected in the Bolzano province (Trentino Alto Adige region) near the Austrian border. The aim of this work was to evaluate the prevalence of infection in red fox populations from five Italian regions. A modified nested PCR analysis was used to detect E. multilocularis DNA in faecal samples. Amplicons were confirmed by sequencing. Of 500 faecal samples from foxes shot in Valle d'Aosta (n=57), Liguria (n=44), Lombardy (n=102), Veneto (n=56), and Trentino Alto Adige (n=241) regions, 24 animals, all from the Trentino Alto Adige region, were found positive. Twenty-two positive animals originated from the Bolzano province and two positive animals from the Trento province. Several localities of the Bolzano province, in which positive foxes were detected, are the same as those where alveolar echinococcosis had been described in humans in the second half of the 19th century, suggesting an old endemicity for the investigated area, which is adjacent to endemic areas of Austria. Therefore, the question arises if we are observing an increase and expansion of foci, or if the new records are due to the more sensitive and specific methods used to detect the worm DNA.     

Elacestrant in metastatic breast cancer: Is the “standard of care” meeting standard requirements?

The EMERALD trial was an open label phase 3 trial evaluating elacestrant, the first oral selective estrogen receptor degrader (SERD), as compared to “standard of care”, in ER+/HER2- (hormone receptor positive, no HER2 overexpression) advanced or metastatic breast cancer.The EMERALD trial restricted the “standard of care” control arm to limited options that may have led to a substandard control arm. We describe how the EMERALD trial protocol allowed different clinically inappropriate scenarios in the control arm, according to prior therapy. The main relevant question remains the potential advantage of elacestrant over fulvestrant in fulvestrant-naive patients.Analyzing outcomes in subgroups according to prior and per-protocol therapy would help analyzing trial results. However, these subgroup results may be non-significant, and another randomized trial will be needed. Trials should be designed to answer directly clinical questions that are relevant.     

Focus: The Science of Stress: What are the Origins of Chronic Back Pain of “Obscure Origins”? Turning Toward Family and Workplace Social Contexts

Chronic back pain (CBP) is a common symptom throughout the world, and those undergoing it often experience a profound degradation of life. Despite extensive research, it remains an elusive symptom. In most cases, CBP is “non-specific,” since bio-mechanisms examined in the clinic do not account for it; another way of saying this is that it is “of obscure origins.” This paper re-directs attention towards origins that are distal and usually out of sight from the vantage point of the clinic. CBP as considered here is non-specific, persists ≥ 3 months, and, additionally, interferes with activities of daily life, such as family interaction or work. A theory proposed in the paper draws upon Durkheim’s Suicide to explain why exposures in the distal social contexts of family and workplace are fundamentally implicated in CBP. The theory is formed out of previously published studies on family and workplace social contexts of CBP and, in effect, provides a theoretical framework with which to review them. After treatment of CBP in the clinic, patients return to family and workplace contexts. Unless exposures in these contexts are addressed, they serve as continually renewing sources of CBP that remain unabated regardless of mechanism-based treatment in the clinic.     

Rabies in urban foxes (Vulpes vulpes) in Britain: the use of a spatial stochastic simulation model to examine the pattern of spread and evaluate the efficacy of different control régimes.

The threat of rabies being reintroduced into Britain is probably greater now than at any time over the last 60 years. This threat is reviewed with particular regard to the problems that would be posed should rabies be introduced to the high-density fox populations found in many cities in southern England. Computer models can provide a valuable means of understanding the pattern of rabies spread in fox populations and the likely problems of control, so the construction of previous rabies models was reviewed. None were found to be suitable for analysing the particular problems posed by high-density, spatially heterogeneous, urban fox populations. Therefore, a new spatial stochastic simulation model was produced, based on demographic and other data collected during a long-term study on the urban fox population in Bristol, and fox density data collected from a number of cities in southern England. The simulation model was used to analyse the effects of spatial heterogeneity in the fox population on the pattern of rabies spread. Simulations were then used to evaluate the effects of: (i) varying levels of fox control; (ii) changing the size of the control zone; (iii) the onset of the rabies epizooty at different times of the year: and (iv) delay before the commencement of control on the chances of containing the disease. These simulations were run for four cities (Bournemouth and Poole, Bristol, Leicester and the West Midlands conurbation) with different mean fox population densities. It was found that the variance in the monthly velocity of the rabies front was greater for heterogeneous fox populations. In cities with high fox densities, low or moderate levels of control were unsuccessful in containing the disease, but these urban areas had the highest rates of success with the highest levels of control. A three-month delay in the commencement of a rabies control campaign on average reduced the chance of successfully controlling the disease by 10-20%, although this was higher in lower-density fox populations. Rabies outbreaks in the dispersal period were on average 10% less likely to be contained. Increasing the size of the control zone increased the chances of successfully containing the disease, although this effect was density dependent, so the effect was less in low-density fox populations. These results are discussed in relation to the current rabies contingency plans for British urban areas.     

Microclimate‐driven trends in spring‐emergence phenology in a temperate reptile (Vipera berus): Evidence for a potential “climate trap”?

Climate change can not only increase the exposure of organisms to higher temperatures but can also drive phenological shifts that alter their susceptibility to conditions at the onset of breeding cycles. Organisms rely on climatic cues to time annual life cycle events, but the extent to which climate change has altered cue reliability remains unclear. Here, we examined the risk of a “climate trap”—a climatically driven desynchronization of the cues that determine life cycle events and fitness later in the season in a temperate reptile, the European adder (Vipera berus). During the winter, adders hibernate underground, buffered against subzero temperatures, and re‐emerge in the spring to reproduce. We derived annual spring‐emergence trends between 1983 and 2017 from historical observations in Cornwall, UK, and related these trends to the microclimatic conditions that adders experienced. Using a mechanistic microclimate model, we computed below‐ and near‐ground temperatures to derive accumulated degree‐hour and absolute temperature thresholds that predicted annual spring‐emergence timing. Trends in annual‐emergence timing and subsequent exposure to ground frost were then quantified. We found that adders have advanced their phenology toward earlier emergence. Earlier emergence was associated with increased exposure to ground frost and, contradicting the expected effects of macroclimate warming, increased post‐emergence exposure to ground frost at some locations. The susceptibility of adders to this “climate trap” was related to the rate at which frost risk diminishes relative to advancement in phenology, which depends on the seasonality of climate. We emphasize the need to consider exposure to changing microclimatic conditions when forecasting biological impacts of climate change.     

“Green Fluff”? The Role of Corporate Sustainability Initiatives in Effective Climate Policy: Comment on “Science‐Based Carbon Targets for the Corporate World: The Ultimate Sustainability Commitment,or a Costly Distraction?”

The commentary by Schendler and Trexler (2015) strikes us as an intriguing paradox. Schendler and Trexler see responses to the threat of global climate change beginning to move forward in the corporate world, but they fear these corporate initiatives will be a distraction from what is ultimately required. They emphasize the need for “greater government intervention.” An earlier text by Schendler and Toffel (2013) notes, and we agree, that “we're failing to deal with the problem at anywhere near sufficient scale.” But we feel that the article by Schendler and Trexler does not adequately acknowledge the importance of these corporate efforts as elements of initiation and leadership. Schendler and Trexler express the impatience that many of us feel regarding the continued failure of political progress at the national and international levels. But they do not embrace the thoughts attributed to the sixth century B.C. Chinese philosopher Lao Tzu: “A journey of a thousand miles begins with a single step.” They fail to acknowledge that, in democratic governments, there is the need for grass‐roots support in order to develop and implement effective policy. Rather than distractions, individual and corporate efforts are generally necessary prerequisites for implementation of and receptiveness to government action. We agree that society is not dealing with climate change at anything approaching the needed scale and that, ultimately, a meaningful government and international response to climate change is required. The challenge is finding the way forward to achieve this outcome. In a first‐best scenario, the global community would simply negotiate an effective international climate agreement. For more than 35 years, individual countries have collaborated to pursue this first‐best scenario, starting with the first World Climate Conference in 1979 and continuing with the United Nations Framework Convention on Climate Change (UNFCCC) and the Kyoto Protocol. But this “top‐down” approach has yielded little success and even less hope, with global carbon dioxide (CO₂) emissions increasing by more than 50% since adoption of the UNFCCC in 1992. While countries agree on the need for an international agreement, “there is disagreement on almost every aspect of the climate change problem. Countries approach the problem in different stages of development and from different development paths, and thus with different perspectives” (Cherry et al. 2014, 23).     

Did ‘precautionary’ 1080 baiting have a realistic potential to eradicate Red Fox (Vulpes vulpes) in Tasmania without in situ monitoring data?

Anecdotal reports in 2001 suggested that the European Red Fox (Vulpes vulpes) had been deliberately released in Tasmania and thereafter an eradication programme using buried fluoroacetic acid (1080) baits was believed to be a necessary precautionary action until mid‐2013. Prerequisites for the successful eradication of foxes relate to the scale of the undertaking and the ability to collect in situ data such as the distribution and abundance of the target population and measures of the efficacy of the control technique. Previously, 1080 baiting has demonstrated only limited potential as a fox eradication technique on islands when used on a scale between 685 and 2141 times smaller than Tasmania. In the absence of empirical monitoring data confirming the distribution or abundance of extant foxes, buried baiting was targeted to specific landscapes believed to be preferred by foxes. No empirical data was collected concerning the in situ effectiveness of baiting in Tasmania, yet an a priori assumption of lethal efficacy was extrapolated from four heterogeneous mainland studies to suggest that foxes would have only a 0.23 probability of surviving each bait treatment. We show that these studies were unrepresentative of Tasmanian baiting methods used and influenced by imprecise fox population surveys and misreported data. Overall, in the absence of key population monitoring and efficacy data, the ‘precautionary’ baiting strategy adopted did not have a realistic potential to eradicate fox incursions in Tasmania, nor is it an appropriate risk management strategy for other large offshore Australian islands. Contingency plans to counter fox incursions on offshore islands must address the currently inadequate technical capacity to reliably detect and monitor low‐density fox populations, which is an essential component of successful fox eradication.     

Will the clinical development of 4th-generation “double mutant active” ALK TKIs (TPX-0131 and NVL-655) change the future treatment paradigm of ALK+ NSCLC?

Our current treatment paradigm of advanced anaplastic lymphoma kinase fusion (ALK+) non-small cell lung cancer (NSCLC) classifies the six currently approved ALK tyrosine kinase inhibitors (TKIs) into three generations. The 2nd-generation (2G) and 3rd-generation (3G) ALK TKIs are all “single mutant active” with varying potencies across a wide spectrum of acquired single ALK resistance mutations. There is a vigorous debate among clinicians which is the best upfront ALK TKI is for the first-line (1L) treatment of ALK+ NSCLC and the subsequent sequencing strategies whether it should be based on the presence of specific on-target ALK resistance mutations or not. Regardless, sequential use of “single mutant active” ALK TKIs will eventually lead to double ALK resistance mutations in cis. This has led to the creation of fourth generation (4G) “double mutant active” ALK TKIs such as TPX-0131 and NVL-655. We discuss the critical properties 4G ALK TKIs must possess to be clinically successful. We proposed conceptual first-line, second-line, and molecularly-based third-line registrational randomized clinical trials designed for these 4G ALK TKIs. How these 4G ALK TKIs would be used in the future will depend on which line of treatment the clinical trial design(s) is adopted provided the trial is positive. If approved, 4G ALK TKIs may usher in a new treatment paradigm for advanced ALK+ NSCLC that is based on classifying ALK TKIs based on the intrinsic functional capabilities (“singe mutant active” versus “double mutant active”) rather than the loosely-defined “generational” (first-, second-,third-,fourth-) classification and avoid the current clinical approaches of seemingly random sequential use of 2G and 3G ALK TKIs.     

Cocirculation of Avian H9N2 and Contemporary “Human” H3N2 Influenza A Viruses in Pigs in Southeastern China: Potential for Genetic Reassortment?

Pigs are permissive to both human and avian influenza viruses and have been proposed to be an intermediate host for the genesis of pandemic influenza viruses through reassortment or adaptation of avian viruses. Prospective virological surveillance carried out between March 1998 and June 2000 in Hong Kong, Special Administrative Region, People's Republic of China, on pigs imported from southeastern China, provides the first evidence of interspecies transmission of avian H9N2 viruses to pigs and documents their cocirculation with contemporary human H3N2 (A/Sydney/5/97-like, Sydney97-like) viruses. All gene segments of the porcine H9N2 viruses were closely related to viruses similar to chicken/Beijing/1/94 (H9N2), duck/Hong Kong/Y280/97 (H9N2), and the descendants of the latter virus lineage. Phylogenetic analysis suggested that repeated interspecies transmission events had occurred from the avian host to pigs. The Sydney97-like (H3N2) viruses isolated from pigs were related closely to contemporary human H3N2 viruses in all gene segments and had not undergone genetic reassortment. Cocirculation of avian H9N2 and human H3N2 viruses in pigs provides an opportunity for genetic reassortment leading to the emergence of viruses with pandemic potential.     

Are all grandmothers equal? A review and a preliminary test of the “grandmother hypothesis” in Tokugawa Japan

An unresolved question arising from human evolutionary research relates to the function of the postreproductive period in human females. If menopause is not merely an artifact resulting from the benefits of civilization, there must be an adaptive mechanism favoring the offspring of women who continue to thrive well past the time of their last ovulation. The "grandmother hypothesis" was developed on the basis of the original suggestion by Williams (1957 Evolution 11:32-39) that "stopping early" would benefit already-born children. This idea, combined with the concepts of kin selection (Hamilton 1964 J Theor Biol 7:1-52) and parental investment (Trivers 1972 Sexual Selection and the Descent of Man, Chicago: Aldine, p. 136-179), was expanded to suggest that postreproductive women (in contrast to males) contribute to their inclusive fitness by extending support to their grandchildren. We used discrete time event history analysis (Allison [1984] Event History Analysis, Newbury Park: Sage; Allison [1995] Survival Analysis, Cary, NC: SAS Institute) and logistic regression on data provided in population registers (Shūmon Aratame Chō, or SAC) from a village in central Japan, covering the period from 1671-1871, in a preliminary investigation of the effects of household grandparental presence on the probability of a child's death. We found that after accounting for the presence of other household members, the only grandparent whose presence exerted a consistent negative effect on the likelihood of a child's death was the mother's mother. Due to the small sample size of households that contained maternal grandmothers, these results failed to achieve statistical significance. Their importance, however, is in what they suggest about future research, i.e., census data from preindustrial societies can provide a basis for testing evolutionary proposals, including the "grandmother hypothesis."     

The German wildlife information system (WILD): population densities and den use of red foxes (<Emphasis Type="Italic">Vulpes vulpes</Emphasis>) and badgers (<Emphasis Type="Italic">Meles meles</Emphasis>) during 2003–2007 in Germany

Monitoring the populations of badgers and red foxes may help us to manage these predator species as a matter of wildlife conservation and regulation. To fit the needs of a monitoring programme, the most practicable method has to be selected. Hunting bag statistics deliver large but inaccurate data amounts with low effort. Indirect and also often direct counts might deliver only presence–absence data with high effort. Direct counts with high accuracy are very costly. Den mapping by volunteer local hunters can deliver reliable data on density and additional biological variables while being feasible and cost effective. Within reference areas all over Germany, fox and badger dens and litters were recorded, and spring and summer densities estimated as well as potential annual population increases were calculated for 2003–2007. Habitat preferences for breeding dens were also analysed. Additionally, in 2006, the distribution of badgers was surveyed by a nationwide questionnaire. Fox and badger are distributed all over Germany with some small gaps and regionally differing densities. During the monitoring period, fox and badger densities and reproduction stayed stable, at a high level corresponding to hunting bags. However, densities varied between geographical regions, with lower densities in the sparsely wooded lowland regions. A preference for forest and habitats offering shelter was clear for breeding setts and dens. Badgers especially preferred setts of natural origin.     

Does the morphology of the ear of the Chinese bamboo rat (Rhizomys sinensis) show “Subterranean” characteristics?

In spite of the growing interest in rodents with subterranean activity in general and the spalacids (Spalacidae) in particular, little is known about the biology of most members of this clade, such as the Chinese bamboo rat (Rhizomys sinensis). Here, we analyzed the ear morphology of R. sinensis with respect to hearing specialization for subterranean or aboveground modes of communication. It is well‐known that ecology and style of life of a particular species can be reflected in morphology of its ear, its hearing and vocalization, so we expect that such information could provide us insight into its style of life and its sensory environment. The ratio between the eardrum and stapedial footplate areas, which influences the efficiency of middle ear sound transmission, suggests low hearing sensitivity, as is typical for subterranean species. The cochlea had 3.25 coils and resembled species with good low frequency hearing typical for subterranean mammals. The length of the basilar membrane was 18.9 ± 0.8 mm and its width slowly increased towards the cochlear apex from 60 to 85 μm. The mean density of outer hair cells was 344 ± 22 and of inner hair cells 114 ± 7.3 per 1 mm length of the organ of Corti, and increased apically. These values (except for relatively low hair cell density) usually characterize ears specialized for low frequency hearing. There was no evidence for an acoustic fovea. Apart of low hair cell density which is common in aboveground animals, this species has also relatively large auricles, suggesting the importance of sound localization during surface activity. The ear of the Chinese bamboo rat thus contains features typical for both aboveground and subterranean mammals and suggests that this spalacid has fossorial habits combined with regular aboveground activity. J. Morphol. 277:575–584, 2016. © 2016 Wiley Periodicals, Inc.     

Are demographic correlates of white-faced capuchin monkey (Cebus capucinus) “Gargle and Twargle” vocalization rates consistent with the infanticide risk assessment hypothesis?

Zahavi's “Bond Testing Hypothesis” states that irritating stimuli are used to elicit honest information from social partners regarding their attitudes towards the relationship. Two elements of the Cebus capucinus vocal repertoire, the “gargle” and “twargle,” have been hypothesized to serve such a bond-testing function. The greatest threat to C. capucinus infant survival, and to adult female reproductive success, is infanticide perpetrated by alpha males. Thus, we predicted that infants (<8 months), pregnant females and females with infants would gargle/twargle at higher rates than the rest of the population, directing these vocalizations primarily to the alpha male. Over 16 years, researchers collected data via focal follows in 11 habituated groups of wild capuchins in Lomas Barbudal, Costa Rica. We found some support for our hypothesis. Infants and females with infants (<8 months) vocalized at higher rates than the rest of the population. Pregnant females did not vocalize at relatively high rates. Infants (age 8–23 months) were the only target group that vocalized more when the alpha male was not their father. Monkeys gargled and twargled most frequently towards the alpha male, who is both the perpetrator of infanticide and the most effective protector against potentially infanticidal males.     

Are there predictable clines in plant–pollinator interactions along altitudinal gradients? The example of Cytisus scoparius (L.) Link in the Sierra de Guadarrama (Central Spain)

Abstract. We analyse the hypothesis that predictable gradients occur in plant–pollinator interactions along altitudinal gradients due to thermal constraints on insect body size and floral traits being selected for by pollinators. Pollinators’ size should follow Bergmann's rule in mountains (larger body size at higher altitudes) and selection should, in turn, lead to larger flower size at higher altitudes. The study focuses on the flower and pollinator size variation in 11 Cytisus scoparius populations located between 680 and 1300 m a.s.l., and on the relationship between flower size and pollination success of plants in each population. Significant differences among populations were found in flower size, pollinator size and fruiting success (anova , P < 0.001 in all cases). Regression models show that (i) pollinator size increases significantly with altitude, (ii) a parallel quadratic increase in flower size and (iii) a quadratic decrease in pollination success with altitude. Moreover, there is a tendency of plants with smaller flowers in each population to have a higher percentage of flowers initiating development into fruits (ancova , P < 0.05). All these observations support the presence of the predicted gradient in the studied species and they suggest the possibility of it to be somewhat common among plants that occupy large altitudinal ranges due to the simple basis on which it could be rooted.     

Can genotypes of soybean (Glycine max) selected for nitrate tolerance provide good “models” for studying the mechanism of nitrate inhibition of nitrogenase activity?

In soybeans ( Glycine max L. Merr.), high levels of soil nitrate inhibit N₂ fixation, and nitrate-tolerant symbioses have been identified within a chemically mutagenized line of cv. Bragg denoted nts382 and within the line K466, a genotype representative of a number of Korean soybean cultivars. The genotypes nts382 and K466 were examined to see if they could be used as a model system for studying the mechanism responsible for the short-term (i.e. 3-day) inhibition of specific nitrogenase activity, especially the mechanism behind the greater O₂ limitation of nodule metabolism that is characteristic of nitrate inhibition of N₂ fixation in soybean. In nts382, total nitrogenase activity (TNA = H₂ production in Ar:O₂) was inhibited to a lesser degree (48% of control) relative to Bragg (30% of control), and the nitrate-treated symbioses showed less of an O₂ limitation of nodule metabolism in nts382 than in Bragg. However, the relative proportion of O₂ limitation to the total nitrate inhibition was similar (40 and 41%) in nts382 and Bragg, respectively. Therefore, the nts382 symbioses may be useful in elucidating the general mechanism for down-regulation of nitrogenase activity in soybean, but would not be a useful model system for studying the control of O₂-limited metabolism following nitrate exposure. The effects of nitrate on TNA and on the degree of O₂ limitation of nodule metabolism were the same in K466 and a reference cultivar Maple Arrow. Consequently, the tolerance of K466 to nitrate reported previously was attributed to the ability of this symbiosis to maintain nodule biomass in the presence of nitrate, not to any ability to maintain specific nitrogenase activity in the presence of nitrate.