Stereotactic ablative body radiotherapy (SABR) is an emerging treatment option for oligometastatic prostate cancer. However, limited prospective evidence is available.
To determine the safety and ...feasibility of single fraction SABR for patients with oligometastatic prostate cancer. Secondary endpoints were local and distant progression-free survival (LPFS and DPFS), toxicity, quality of life (QoL), and prostate-specific antigen response.
In a prospective clinical trial, patients were screened with computed tomography, bone scan, and sodium fluoride positron emission tomography scan and had one to three oligometastases. Kaplan-Meier methods were used to determine LPFS and DPFS. Toxicity was graded using Common Terminology Criteria for Adverse Event version 4.0. QoL was assessed using European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-BM22 at 1, 3,12, and 24 mo.
A single fraction of 20-Gy SABR to each lesion.
Between 2013 and 2014, 33 consecutive patients received SABR to a total of 50 oligometastases and were followed for 2 yr. The median age was 70 yr. The Gleason score was ≥8 in 15 patients (45%). Twenty patients had bone only, 12 had node only, and one had mixed disease. SABR was feasible and delivered as planned in 97% of cases. There was one grade 3 adverse event (3.0%, vertebral fracture). No patient died. The 1 and 2-yr LPFS was 97% (95% confidence interval CI: 91–100) and 93% (95% CI: 84–100), and DPFS was 58% (95% CI: 43–77) and 39% (95% CI: 25–60), respectively. In those not on androgen deprivation therapy (ADT; n=22), the 2-yr freedom from ADT was 48%. There was no significant difference from baseline QoL observed. Limitations include small sample size, limited duration of follow-up, and lack of a control arm.
A single SABR session was feasible and associated with low morbidity in this cohort. Over one-third of patients did not progress and were free from ADT at 2-yr. QoL measures were maintained with this treatment strategy.
This clinical trial investigated single treatment stereotactic radiotherapy for low volume advanced prostate cancer. The approach was found to be safe with avoidance of hormone therapy in almost half of the participants at 2 yr.
For patients with one to three oligometastases from prostate cancer, single fraction 20-Gy stereotactic ablative body radiotherapy was both safe and feasible. Local and distant progression-free survival at 2 yr were 93% and 39%, respectively. Quality of life was maintained at baseline levels using this treatment strategy.
Large areas of forests are annually damaged or destroyed by outbreaking insect pests. Understanding the factors that trigger and terminate such population eruptions has become crucially important, as ...plants, plant‐feeding insects, and their natural enemies may respond differentially to the ongoing changes in the global climate. In northernmost Europe, climate‐driven range expansions of the geometrid moths Epirrita autumnata and Operophtera brumata have resulted in overlapping and increasingly severe outbreaks. Delayed density‐dependent responses of parasitoids are a plausible explanation for the 10‐year population cycles of these moth species, but the impact of parasitoids on geometrid outbreak dynamics is unclear due to a lack of knowledge on the host ranges and prevalences of parasitoids attacking the moths in nature. To overcome these problems, we reviewed the literature on parasitism in the focal geometrid species in their outbreak range and then constructed a DNA barcode reference library for all relevant parasitoid species based on reared specimens and sequences obtained from public databases. The combined recorded parasitoid community of E. autumnata and O. brumata consists of 32 hymenopteran species, all of which can be reliably identified based on their barcode sequences. The curated barcode library presented here opens up new opportunities for estimating the abundance and community composition of parasitoids across populations and ecosystems based on mass barcoding and metabarcoding approaches. Such information can be used for elucidating the role of parasitoids in moth population control, possibly also for devising methods for reducing the extent, intensity, and duration of outbreaks.
We present a curated DNA barcode database for all parasitoid species associated with two geometrid species (Epirrita autumnata and Operophtera brumata) undergoing cyclic population outbreaks in the subarctic mountain birch forests that form the treeline in northern Europe. Our vetted database of host–parasitoid records and parasitoid barcodes constitutes a resource that can be used for barcoding‐ and metabarcoding‐based research on the significance of parasitoids for moth population control. Our barcode library will also enable molecular‐genetic monitoring of climate‐driven latitudinal shifts in moth–parasitoid networks and will facilitate the design of measures aiming at reducing the frequency and extent of moth outbreaks in northern European treeline forests.
A checklist of world species of Microgastrinae parasitoid wasps (Hymenoptera: Braconidae) is provided. A total of 81 genera and 2,999 extant species are recognized as valid, including 36 nominal ...species that are currently considered as
. Two genera are synonymized under
. Nine lectotypes are designated. A total of 318 new combinations, three new replacement names, three species name amendments, and seven species status revised are proposed. Additionally, three species names are treated as
, and 52 species names are considered as unavailable names (including 14 as
). A total of three extinct genera and 12 extinct species are also listed. Unlike in many previous treatments of the subfamily, tribal concepts are judged to be inadequate, so genera are listed alphabetically. Brief diagnoses of all Microgastrinae genera, as understood in this paper, are presented. Illustrations of all extant genera (at least one species per genus, usually more) are included to showcase morphological diversity. Primary types of Microgastrinae are deposited in 108 institutions worldwide, although 76% are concentrated in 17 collections. Localities of primary types, in 138 countries, are reported. Recorded species distributions are listed by biogeographical region and by country. Microgastrine wasps are recorded from all continents except Antarctica; specimens can be found in all major terrestrial ecosystems, from 82°N to 55°S, and from sea level up to at least 4,500 m a.s.l. The Oriental (46) and Neotropical (43) regions have the largest number of genera recorded, whereas the Palaearctic region (28) is the least diverse. Currently, the highest species richness is in the Palearctic region (827), due to more historical study there, followed by the Neotropical (768) and Oriental (752) regions, which are expected to be the most species rich. Based on ratios of Lepidoptera and Microgastrinae species from several areas, the actual world diversity of Microgastrinae is expected to be between 30,000-50,000 species; although these ratios were mostly based on data from temperate areas and thus must be treated with caution, the single tropical area included had a similar ratio to the temperate ones. Almost 45,000 specimens of Microgastrinae from 67 different genera (83% of microgastrine genera) have complete or partial DNA barcode sequences deposited in the Barcode of Life Data System; the DNA barcodes represent 3,545 putative species or Barcode Index Numbers (BINs), as estimated from the molecular data. Information on the number of sequences and BINs per genus are detailed in the checklist. Microgastrinae hosts are here considered to be restricted to Eulepidoptera, i.e., most of the Lepidoptera except for the four most basal superfamilies (Micropterigoidea, Eriocranioidea, Hepialoidea and Nepticuloidea), with all previous literature records of other insect orders and those primitive Lepidoptera lineages being considered incorrect. The following nomenclatural acts are proposed: 1) Two genera are synonymyzed under
:
Kieffer & Jörgensen, 1910,
and
Cameron, 1905,
; 2) Nine
are made for
(Ashmead, 1900),
(Ashmead, 1900),
(Marshall, 1885),
(Ashmead, 1900),
(Marshall, 1889),
(Wilkinson, 1932),
(Cameron, 1911),
(Walsh, 1861), and
Ashmead, 1900; 3) Three
are a)
Fernandez-Triana, replacing
(Rao & Chalikwar, 1970) nec
(Wilkinson, 1927), b)
Fernandez-Triana, replacing
Liu & Chen, 2019 nec
Fagan-Jeffries & Austin, 2019, and c)
Fernandez-Triana, replacing
Tobias, 1964 nec
Viereck, 1917; 4) Three
are
Fernandez-Triana, 2014,
(Brèthes, 1920), and
(Porter, 1916); 5) Seven species have their
:
(Thomson, 1895),
(Watanabe, 1921),
(Tobias, 1986),
(Telenga, 1949),
(Capek & Zwölfer, 1957),
Nixon, 1965, and
(Wilkinson, 1932); 6)
are given for 318 species:
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In patients with oligometastatic renal cell carcinoma, radiotherapy to all metastases followed by short-course pembrolizumab is safe, with a grade 3 adverse event rate of 13%. The combination is ...effective, with median progression-free survival of 15.6 mo and 2-yr local control of 92%.
Stereotactic ablative body radiotherapy (SABR) is an option for oligometastatic clear cell renal cell carcinoma (ccRCC) but is limited by a lack of prospective clinical trial data.
The RAPPORT trial evaluated the safety and efficacy of total metastatic irradiation followed by short-course anti–programmed death receptor-1 immunotherapy in patients with oligometastatic ccRCC.
RAPPORT was a single-arm multi-institutional phase I/II trial (NCT02855203). Patients with two or fewer lines of prior systemic therapy and one to five oligometastases from ccRCC were eligible.
A single fraction of 20 Gy SABR (or if not feasible, ten fractions of 3 Gy) was given to all metastatic sites, followed by pembrolizumab 200 mg administered Q3W for eight cycles.
The endpoints were adverse events (AEs), disease control rate (DCR) for at least 6 mo, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The Kaplan-Meier method was used for time-to-event endpoints. Freedom from local progression (FFLP) was assessed per lesion adding patient as a cluster effect.
Thirty evaluable patients, with a median age of 62 yr, were enrolled. The median follow-up was 28 mo. There were 44% of patients with intermediate-risk and 56% with favorable-risk disease. Eighty-three oligometastases were irradiated (median three per patient): eight adrenal, 11 bone, 43 lung, 12 lymph node, and nine soft tissue. Four patients (13%) had grade 3 treatment-related AEs: pneumonitis (n = 2), dyspnea (n = 1), and elevated alkaline phosphatase/alanine transaminase (n = 1). There were no grade 4 or 5 AEs. FFLP at 2 yr was 92%. ORR was 63% and DCR was 83%. Estimated 1- and 2-yr OS was 90% and 74%, respectively, and PFS was 60% and 45%, respectively. Limitations include a single-arm design and selected patient population.
SABR and short-course pembrolizumab in oligometastatic ccRCC is well tolerated, with excellent local control. Durable responses and encouraging PFS were observed, warranting further investigation.
The RAPPORT trial investigated the combination of high-dose precision radiotherapy and a short course of immunotherapy in patients with low-volume metastatic kidney cancer. We found that this treatment regimen was well tolerated, with excellent cancer control in sites of known disease. A proportion of patients were free from cancer relapse in the longer term, and these encouraging findings warrant further investigation.
The debate regarding the ideal response to organised crime is quickly evolving, although it remains often remarkably disconnected from the even more rapidly moving discussion on drugs. One important ...connection between these two debates is the application of a similar set of terminology – namely that of harm reduction. Harm reduction focuses on examining policy responses in ways which both highlight prevention and individual and community impacts, including the impact of law enforcement itself. If such a lens is applied to organised crime it is suggested that the three areas of focus should be: the reducing of violence; protecting political processes, and reducing impunity through high level and “symbolic” prosecutions.
Wolbachia is a genus of bacterial endosymbionts that impacts the breeding systems of their hosts. Wolbachia can confuse the patterns of mitochondrial variation, including DNA barcodes, because it ...influences the pathways through which mitochondria are inherited. We examined the extent to which these endosymbionts are detected in routine DNA barcoding, assessed their impact upon the insect sequence divergence and identification accuracy, and considered the variation present in Wolbachia COI. Using both standard PCR assays (Wolbachia surface coding protein--wsp), and bacterial COI fragments we found evidence of Wolbachia in insect total genomic extracts created for DNA barcoding library construction. When >2 million insect COI trace files were examined on the Barcode of Life Datasystem (BOLD) Wolbachia COI was present in 0.16% of the cases. It is possible to generate Wolbachia COI using standard insect primers; however, that amplicon was never confused with the COI of the host. Wolbachia alleles recovered were predominantly Supergroup A and were broadly distributed geographically and phylogenetically. We conclude that the presence of the Wolbachia DNA in total genomic extracts made from insects is unlikely to compromise the accuracy of the DNA barcode library; in fact, the ability to query this DNA library (the database and the extracts) for endosymbionts is one of the ancillary benefits of such a large scale endeavor--which we provide several examples. It is our conclusion that regular assays for Wolbachia presence and type can, and should, be adopted by large scale insect barcoding initiatives. While COI is one of the five multi-locus sequence typing (MLST) genes used for categorizing Wolbachia, there is limited overlap with the eukaryotic DNA barcode region.
Climate and land use change can alter the incidence and strength of biotic interactions, with important effects on the distribution, abundance and function of species. To assess the importance of ...these effects and their dynamics, studies quantifying how biotic interactions change in space and time are needed.
We studied interactions between nettle‐feeding butterflies and their shared natural enemies (parasitoids) locally and across 500 km latitudinal gradient in Sweden. We also examined the potential impact of the range‐expansion of the butterfly Araschnia levana on resident butterflies via shared parasitoids, by studying how parasitism in resident butterflies covaries with the presence or absence of the newly‐established species. We collected 6777 larvae of four nettle‐feeding butterfly species (Aglais urticae, Aglais io, Ar. levana and Vanessa atalanta), over two years, at 19 sites distributed along the gradient. We documented the parasitoid complex for each butterfly species and measured their overlap, and analysed how parasitism rates were affected by butterfly species assemblage, variations in abundance, time, and the arrival of Ar. levana. Parasitoids caused high mortality, with substantial overlap in the complex of parasitoids associated with the four host butterflies. Levels of parasitism differed significantly among butterflies and were influenced by the local butterfly species assemblage. Our results also suggest that parasitism in resident butterflies is elevated at sites where Ar. levana has been established for a longer period.
In our study system, variations in butterfly species assemblages were associated in a predictable way with substantial variations in rates of parasitism. This relationship is likely to affect the dynamics of the butterfly host species, and potentially cascade to the larger number of species with which they interact. These results highlight the importance of indirect interactions and their potential to reorganise ecological communities, especially in the context of shifts in species distributions in a warmer world.
Parasitism is a key factor in the population dynamics of many herbivorous insects, although its impact on host populations varies widely, for instance, along latitudinal and altitudinal gradients. ...Understanding the sources of geographical variation in host–parasitoid interactions is crucial for reliably predicting the future success of the interacting species under a context of global change.
Here, we examine larval parasitism in the butterfly Aglais urticae in south‐west Europe, where it is a mountain specialist. Larval nests were sampled over 2 years along altitudinal gradients in three Iberian mountain ranges, including the Sierra Nevada, home to its southernmost European population. Additional data on nettle condition and adult butterflies were obtained in the study areas.
These data sources were used to investigate whether or not differences in parasitism rates are related to the geographical position and phenology of the host, and to the availability of the host plants.
Phenological differences in the host populations between regions were related to the severity of summer drought and the corresponding differences in host plant availability. At the trailing‐edge of its distribution, the butterfly's breeding season was restricted to the end of winter and spring, while in its northern Iberian range the season was prolonged until mid‐summer. Although parasitism was an important source of mortality in all regions, parasitism rates and parasitoid richness were highest in the north and lowest in the south. Moreover, within a region, there was a notable increase in parasitism rates over time, which probably led to selection against an additional late summer host generation in northern regions. Conversely, the shorter breeding season in Sierra Nevada resulted in a loss of synchrony between the host and one important late season parasitoid, Sturmia bella, which may partly explain the high density of this butterfly species at the trailing‐edge of its range.
Our results support the key role of host phenology in accounting for differences in parasitism rates between populations. They also provide insights into how climate through host plant availability affects host phenology and, ultimately, the impact of parasitism on host populations.
Experienced parasitoid taxonomists, together with butterfly ecologists characterize the parasitoid assemblages associated with the iconic Aglais urticae along a latitudinal gradient. They find that parasitism is a major source of mortality and provide insights into how different environmental conditions translate into differences in the impact of parasitism.
Aim
Low body fat percentage (BF%) has been shown to predict morbidity and possible hypoglycaemia in newborns. Hypoglycaemia in neonates is associated with significant neonatal morbidity. Early ...detection and prevention are critical. To identify if low BF% (>1 standard deviation below the mean) in non‐small‐for‐gestational‐age neonates (>5th percentile body weight) increases the risk of short‐term morbidity, with specific attention to hypoglycaemia.
Methods
All term neonates who had their BF% measured as part of the Newborn Early Assessment Programme between 28 January 2014 and 9 August 2016 were included in the study. Neonates whose weight was below the 5th percentile and neonates of diabetic mothers were excluded as blood sugar level monitoring is routinely performed on these babies. Neonatal morbidity and blood sugar levels were obtained from electronic records, and the individual patient's paper records were reviewed. A composite score for neonatal morbidity (poor feeding AND hypothermia AND prolonged length of stay) was calculated. Statistics were analysed using SPSS.
Results
A total of 247 neonates met the inclusion criteria (3.3% of total births). Hypoglycaemia was found in 8.5% of the study population. The risk of hypoglycaemia did not change significantly in neonates with birthweight of the 5th–10th percentile and >10th percentile (8 vs. 8.8%); 4.9% of babies met the combined morbidity criteria.
Conclusions
Non‐small‐for‐gestational‐age babies (>5th percentile) with low BF% are at risk of hypoglycaemia and short‐term morbidity. These infants will not be identified by current hypoglycaemia screening methods in centres that do not measure BF%.
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