Explore the vast range of titles available.

In a phase 2 trial, bepirovirsen, an antisense oligonucleotide that targets all hepatitis B virus mRNAs, resulted in sustained loss of hepatitis B surface antigen and HBV DNA in 9 to 10% of participants with chronic HBV infection.

The maintenance of biodiversity in tropical forests is thought to be dependent on fine-scale mechanisms of niche partitioning that allow species to coexist. This study examined whether three species of short-tailed fruit bat that co-occur at a lowland tropical forest site in Costa Rica (Carollia castanea, C. perspicillata, C. sowelli) avoid inter- and intraspecific competition through dietary specialization on species in the genus Piper. First, dietary composition was examined using faecal samples (N = 210), which yielded three main findings: (1) bat species and sexes vary in overall reliance on fruits of Piper, with a higher percentage of seeds of Piper detected in the diets of C. castanea (98.2%) and females (91.5%); (2) adults and juveniles partition species of Piper by habitat, with a lower percentage of mid- to late-successional species of Piper detected in adults (20.8%); and (3) overall, there is a strong dietary overlap among and within the three species of Carollia. Second, controlled choice experiments were conducted with individual bats (N = 123) to examine preferences for different species of Piper. These results indicated few differences in Piper preference based on bat species, sex, age class or reproductive status, suggesting preference is not the primary mechanism shaping the observed differences in dietary composition. Overall, the dietary composition and preference similarities suggest there is strong competition both among and within the three species of Carollia for food resources.

The necessary margin of excision for cutaneous melanomas greater than 2 mm in thickness is controversial. At a median follow-up of 5 years, findings from our previously published randomised trial of narrow (1 cm) versus wide (3 cm) excision margins in patients with thick cutaneous melanomas showed that narrow margins were associated with an increased frequency of locoregional relapse, but no significant difference in overall survival was apparent. We now report a long-term survival analysis of that trial. We did a randomised, open-label multicentre trial in 59 hospitals—57 in the UK, one in Poland, and one in South Africa. Patients with one primary localised cutaneous melanoma greater than 2 mm in Breslow thickness on the trunk or limbs (excluding palms or soles) were randomly assigned (1:1) centrally to receive surgery with either a 1 cm or 3 cm excision margin following an initial surgery. The randomisation lists were generated with random permuted blocks and stratified by centre and extent of initial surgery. The endpoints of this analysis were overall survival and melanoma-specific survival. Analyses were done in the intention-to-treat population. This trial was not registered because it predated mandatory trial registration. Between Dec 16, 1992, and May 22, 2001, we randomly assigned 900 patients to surgery with either a 1 cm excision margin (n=453) or a 3 cm excision margin (n=447). At a median follow-up of 8·8 years (106 months [IQR 76–135], 494 patients had died, with 359 of these deaths attributed to melanoma. 194 deaths were attributed to melanoma in the 1 cm group compared with 165 in the 3 cm group (unadjusted hazard ratio [HR] 1·24 [95% CI 1·01–1·53]; p=0·041). Although a higher number of deaths overall occurred in the 1 cm group compared with the 3 cm group (253 vs 241), the difference was not significant (unadjusted HR 1·14 [95% CI 0·96–1·36]; p=0·14). Surgical complications were reported in 35 (8%) patients in the 1 cm excision margin group and 65 (15%) patients in the 3 cm group. Our findings suggest that a 1 cm excision margin is inadequate for cutaneous melanoma with Breslow thickness greater than 2 mm on the trunk and limbs. Current guidelines advise a 2 cm margin for melanomas greater than 2 mm in thickness but only a 1 cm margin for thinner melanomas. The adequacy of a 1 cm margin for thinner melanomas with poor prognostic features should be addressed in future randomised studies. Cancer Research UK, North Thames National Health Service Executive, Northern and Yorkshire National Health Service Executive, British United Provident Association Foundation, British Association of Plastic Surgeons, the Meirion Thomas Cancer Research Fund, and the National Institute for Health and Research Biomedical Research Centre at The Royal Marsden NHS Foundation Trust.

Deciphering the ecological roles of plant secondary metabolites requires integrative studies that assess both the allocation patterns of compounds and their bioactivity in ecological interactions. Secondary metabolites have been primarily studied in leaves, but many are unique to fruits and can have numerous potential roles in interactions with both mutualists (seed dispersers) and antagonists (pathogens and predators). We described 10 alkenylphenol compounds from the plant species Piper sancti-felicis (Piperaceae), quantified their patterns of intraplant allocation across tissues and fruit development, and examined their ecological role in fruit interactions. We found that unripe and ripe fruit pulp had the highest concentrations and diversity of alkenylphenols, followed by flowers; leaves and seeds had only a few compounds at detectable concentrations. We observed a nonlinear pattern of alkenylphenol allocation across fruit development, increasing as flowers developed into unripe pulp then decreasing as pulp ripened. This pattern is consistent with the hypothesis that alkenylphenols function to defend fruits from pre-dispersal antagonists and are allocated based on the contribution of the tissue to the plant’s fitness, but could also be explained by non-adaptive constraints. To assess the impacts of alkenylphenols in interactions with antagonists and mutualists, we performed fungal bioassays, field observations, and vertebrate feeding experiments. In fungal bioassays, we found that alkenylphenols had a negative effect on the growth of most fungal taxa. In field observations, nocturnal dispersers (bats) removed the majority of infructescences, and diurnal dispersers (birds) removed a larger proportion of unripe infructescences. In feeding experiments, bats exhibited an aversion to alkenylphenols, but birds did not. This observed behavior in bats, combined with our results showing a decrease in alkenylphenols during ripening, suggests that alkenylphenols in fruits represent a trade-off (defending against pathogens but reducing disperser preference). These results provide insight into the ecological significance of a little studied class of secondary metabolites in seed dispersal and fruit defense. More generally, documenting intraplant spatiotemporal allocation patterns in angiosperms and examining mechanisms behind these patterns with ecological experiments is likely to further our understanding of the evolutionary ecology of plant chemical traits.

Bats are important pest control agents in agriculture. Yet, the underlying fine‐scale biotic and abiotic mechanisms that drive their foraging behaviors and responses to insect outbreaks are unclear. Herbivore‐induced plant volatiles (HIPVs) can attract both invertebrate and vertebrate natural enemies that use the chemical plant cues to locate insect prey. The ability of HIPVs to attract multiple species raises the question of whether they may also be a biotic factor influencing insectivorous bat activity. Additionally, abiotic factors, such as weather conditions, can affect bat activity in agricultural settings, but little is known about how bats respond to shifting environmental conditions on short timescales in this landscape context. Using a model crop system, soybean (Glycine max), our study asked three questions: (1) Which bat species are active in eastern Maryland soybean fields? (2) Is insectivorous bat activity affected by naturally occurring soybean HIPVs and/or synthetic soybean HIPVs (indole or farnesene)? (3) How is insectivorous bat activity affected by hourly weather conditions in this landscape? In soybean fields in eastern Maryland, we created paired treatment plots: HIPV plots (damaged plants or synthetic HIPV dispensers) and control plots (undamaged plants or empty dispensers). We measured bat activity using ultrasonic recorders, summarizing hourly and nightly activity, and detected 10 total species. The most abundant species were big brown/silver‐haired bats (Eptesicus fuscus/Lasionycteris noctivagans). Bat activity did not significantly differ between control and HIPV plots in any of the three experiments. Thus, our results do not support our expectation that bats in eastern Maryland use soybean HIPVs to locate insect prey. However, bat activity did increase with increasing average hourly temperature and wind speed. This initial study of bats and HIPVs, as well as the fine‐scale examination of weather conditions on bat activity, may serve as a guide for future research on bat–plant interactions that can support the development of new strategies for sustainable pest management.

Hyperbaric oxygen has been used as a therapy for patients experiencing chronic intestinal syndromes after pelvic radiotherapy for decades, yet the evidence to support the use of this therapy is based almost exclusively on non-randomised studies. We aimed to provide conclusive results for the clinical benefits of hyperbaric oxygen in patients with chronic bowel dysfunction after radiotherapy for pelvic malignancies. HOT2 was a double-blind, sham-controlled, phase 3 randomised study of patients (≥18 years) with chronic gastrointestinal symptoms for 12 months or more after radiotherapy and which persisted despite at least 3 months of optimal medical therapy and no evidence of cancer recurrence. Participants were stratified by participating hyperbaric centre and randomly assigned (2:1) by a computer-generated list (block size nine or 12) to receive treatment with hyperbaric oxygen therapy or sham. Participants in the active treatment group breathed 100% oxygen at 2·4 atmospheres of absolute pressure (ATA) and the control group breathed 21% oxygen at 1·3 ATA; both treatment groups received 90-min air pressure exposures once daily for 5 days per week for a total of 8 weeks (total of 40 exposures). Staff at the participating hyperbaric medicine facilities knew the allocated treatment, but patients, clinicians, nurse practitioners, and other health-care professionals associated with patients' care were masked to treatment allocation. Primary endpoints were changes in the bowel component of the modified Inflammatory Bowel Disease Questionnaire (IBDQ) score and the IBDQ rectal bleeding score 12 months after start of treatment relative to baseline. The primary outcome was analysed in a modified intention-to-treat population, excluding patients who did not provide IBDQ scores within a predetermined time-frame. All patients have completed 12 months of follow-up and the final analysis is complete. The trial is registered with the ISRCTN registry, number ISRCTN86894066. Between Aug 14, 2009, and Oct 23, 2012, 84 participants were randomly assigned: 55 to hyperbaric oxygen and 29 to sham control. 75 (89%) participants received 40 pressure exposures, all participants returned the IBDQ at baseline, 75 (89%) participants returned the IBDQ at 2 weeks post-treatment, and 79 (94%) participants returned the IBDQ at 12 months post-start of treatment. Patients were excluded from analyses of co-primary endpoints if they had missing IBDQ scores for intestinal function or rectal bleeding at baseline or at 12 months. In an analysis of 46 participants in the active treatment group and 23 participants in the control group, we found no significant differences in the change of IBDQ bowel component score (median change from baseline to 12 months of 4 (IQR −3 to 11) in the treatment group vs 4 (−6 to 9) in the sham group; Mann-Whitney U score 0·67, p=0·50). In an analysis of 29 participants in the active treatment group and 11 participants in the sham group with rectal bleeding at baseline, we also found no significant differences in the change of IBDQ rectal bleeding score (median change from baseline to 12 months of 3 [1 to 3] in the treatment group vs 1 [1 to 2] in the sham group; U score 1·69, p=0·092). Common adverse events in both groups were eye refractive changes (three [11%] of 28 patients in the control group vs 16 [30%] of 53 patients in the treatment group), increased fatigue (three [11%] vs two [4%]), and ear pain (six [21%] vs 15 [28%]). Eight serious adverse events were reported in eight patients: two were reported in two patients in the control group (tonsillitis requiring surgery [grade 3]; recurrent cancer of the vulva [grade 4]) and six serious adverse events were reported in six patients in the treatment group (malignant spinal cord compression requiring surgery [grade 3]; malignant paraortic lymph node involvement requiring surgery [grade 3]; recurrence of vomiting and dehydration [grade 3]; diarrhoea and fever associated with Campylobacter infection [grade 3]; recurrence of abdominal pain, bloating, diarrhoea, and urinary tract infection [grade 3]; aneurysm [grade 4]), none of which were deemed treatment-related. We found no evidence that patients with radiation-induced chronic gastrointestinal symptoms, including those patients with rectal bleeding, benefit from hyperbaric oxygen therapy. These findings contrast with evidence used to justify current practices, and more level 1 evidence is urgently needed. Cancer Research UK and National Health Service (NHS) funding to the National Institute of Health Research Biomedical Research Centre at The Royal Marsden and the Institute of Cancer Research.

Climate change is a mounting global issue, but its consequences will be variable across regions. Tropical species are hypothesized to have reduced climatic adaptability and plasticity. Yet, relative to temperate species, less is understood about how they will respond to climate change. Rising temperature and atmospheric CO2 could impact plant–herbivore systems directly by altering species traits or abundances, or the effects could be indirect by altering the strength and direction of the relationships that govern organismal strategies and interactions. Using open‐top chambers in a Neotropical wet forest, we applied a full‐factorial combination of active warming and CO2 fertilization to investigate the above‐ground, short‐term effects of climate change on plant–herbivore interactions in a common Neotropical shrub, Piper generalense. We aimed to answer two main questions: (1) Could climate change alter plant–herbivore systems through direct effects on plant growth rate, chemical defense, and/or insect herbivore damage rate? and (2) Could climate change affect plant–herbivore systems indirectly by altering (a) the strength of plant resource allocation trade‐offs between growth and defense or (b) the effectiveness of plant chemical defense against herbivory? None of the microclimate treatments had direct effects on plant growth, chemical defense, or herbivore damage. However, we did observe a positive relationship between growth and chemical defense in treatments mimicking climate‐change conditions, which partially supports the growth–differentiation balance hypothesis. We did not detect any effects of treatments on the effectiveness of plant chemical defense against herbivory. It appears that, in this system, increased CO2 concentration and temperature may cause indirect, cascading consequences, even where direct effects are not observable. We recommend more climate‐change experiments addressing multi‐trophic interactions that focus not only on the direct responses of organisms but also on the ways in which climate change can restructure the relationships that govern complex biotic systems. Climate change could impact plant–herbivore systems directly by altering species traits or abundances or indirectly by altering the strength and direction of the relationships that govern organismal strategies and interactions. It appears that, in this Neotropical system, increased CO2 concentration and temperature may cause indirect, cascading consequences, even where direct effects are not observable.

Specialist herbivores are thought to often enhance or maintain plant diversity within ecosystems, because they prevent their host species from becoming competitively dominant. In contrast, specialist herbivores are not generally expected to have negative impacts on non-hosts. However, we describe a cascade of indirect interactions whereby a specialist sooty mold (Scorias spongiosa) colonizes the honeydew from a specialist beech aphid (Grylloprociphilus imbricator), ultimately decreasing the survival of seedlings beneath American beech trees (Fagus grandifolia). A common garden experiment indicated that this mortality resulted from moldy honeydew impairing leaf function rather than from chemical or microbial changes to the soil. In addition, aphids consistently and repeatedly colonized the same large beech trees, suggesting that seedling-depauperate islands may form beneath these trees. Thus this highly specialized three-way beech-aphid-fungus interaction has the potential to negatively impact local forest regeneration via a cascade of indirect effects.

The high rate of non-radiation-related syndromes diagnosed by an investigational algorithm minimises the recruitment of patients with problems unrelated to radiotherapy, such as bacterial overgrowth after cytotoxic chemotherapy.6 The 3-month run-in period on optimal medical therapies ensures that hyperbaric oxygen therapy is tested only in patients with radiation morbidity refractory to standard management. [...]arguments against the future use of sham controls are seriously misplaced, considering the numerous sources of bias to which unblinded trials are vulnerable, including spontaneous improvements in symptoms.8,9 Based on international criteria, such as those applied by the Federal Drug Administration or Cochrane Collaboration, further well-designed sham-controlled randomised trials are urgently needed.

Specialist herbivores are often thought to benefit the larger plant community, because they prevent their host species from becoming competitively dominant. In contrast, specialist enemies are not generally expected to have negative impacts on non-hosts. However, we describe a cascade of indirect interactions whereby a specialist sooty mold (Scorias spongiosa) colonizes the honeydew from a specialist beech aphid (Grylloprociphilus imbricator), ultimately decreasing the survival of seedlings beneath American beech trees (Fagus grandifolia). A common garden experiment indicated that this mortality resulted from moldy honeydew impairing leaf function rather than from chemical or microbial changes to the soil. In addition, aphids consistently colonized the same beech trees regardless of host density, suggesting that seedling-depauperate islands may form beneath these trees. Thus this highly specialized three-way beech-aphid-fungus interaction has the potential to impact local forest regeneration via a cascade of indirect effects.