Although twins often participate in medical research, few clinical trials are conducted entirely in twin populations. The purpose of this review is to demonstrate the substantial benefits and address the key challenges of conducting clinical trials in twin populations, or ‘twin-only trials’. We consider the unique design, analysis, recruitment and ethical issues that arise in such trials. In particular, we describe the different approaches available for randomizing twin pairs, highlight the similarity or correlation that exists between outcomes of twins, and discuss the impact of this correlation on sample size calculations and statistical analysis methods for estimating treatment effects. We also consider the role of both monozygotic and dizygotic twins for studying variation in outcomes, the factors that may affect recruitment of twins, and the ethics of conducting trials entirely in twin populations. The advantages and disadvantages of conducting twin-only trials are also discussed. Finally, we recommend that twin-only trials should be considered more often.

Altered autobiographical memory (ABM) processing characterizes some individuals with experiences of childhood maltreatment. This fMRI study of ABM processing evaluated potential developmental plasticity in neural functioning following maltreatment. Adolescents with (N = 19; MT group) and without (N = 18; Non-MT group) documented childhood maltreatment recalled specific ABMs in response to emotionally valenced cue words during fMRI at baseline (age 12.71 ± 1.48) and follow-up (14.88 ± 1.53 years). Psychological assessments were collected at both timepoints. Longitudinal analyses were carried out with BOLD signal changes during ABM recall and psychopathology to investigate change over time. In both groups there was relative stability of the ABM brain network, with some developmental maturational changes observed in cortical midline structures (ventromedial PFC (vmPFC), posterior cingulate cortex (pCC), and retrosplenial cortex (rSC). Significantly increased activation of the right rSC was observed only in the MT group, which was associated with improved psychological functioning. Baseline group differences in relation to hippocampal functioning, were not detected at follow-up. This study provides preliminary empirical evidence of functional developmental plasticity in children with documented maltreatment experience using fMRI. This suggests that altered patterns of brain function, associated with maltreatment experience, are not fixed and may reflect the potential to track a neural basis of resilience.

Introduced mammalian predators are responsible for the decline and extinction of many native species, with rats (genus Rattus) being among the most widespread and damaging invaders worldwide. In a naturally fragmented landscape, we demonstrate the multi-year effectiveness of snap traps in the removal of Rattus rattus and Rattus exulans from lava-surrounded forest fragments ranging in size from <0.1 to >10 ha. Relative to other studies, we observed low levels of fragment recolonization. Larger rats were the first to be trapped, with the average size of trapped rats decreasing over time. Rat removal led to distinct shifts in the foraging height and location of mongooses and mice, emphasizing the need to focus control efforts on multiple invasive species at once. Furthermore, because of a specially designed trap casing, we observed low non-target capture rates, suggesting that on Hawai‘i and similar islands lacking native rodents the risk of killing non-target species in snap traps may be lower than the application of rodenticides, which have the potential to contaminate food webs. These efforts demonstrate that targeted snap-trapping is an effective removal method for invasive rats in fragmented habitats and that, where used, monitoring of recolonization should be included as part of a comprehensive biodiversity management strategy.

Background: Carbapenem-resistant Enterobacteriaceae (CRE) are an important cause of healthcare-associated infections (HAIs) in human hospitals. The Philadelphia Department of Public Health (PDPH) made CRE reportable in April 2018. In May 2019, the Matthew J. Ryan Veterinary Hospital (MJRVH) reported an NDM-5 Escherichia coli cluster in companion animals to the PDPH. In total, 15 infected animals (14 dogs and 1 cat) were reported between July 2018 and June 2019, with no new infections after June 2019. Limited literature is available on the prevalence of CRE in companion animals, and recommendations for dealing with CRE infections currently target human healthcare settings. Methods: A collaborative containment response included assessing interspecies transmission to veterinary staff and a comprehensive evaluation of the infection control program at MJRVH. MJRVH notified all owners of affected animals verbally and via notification letters with PDPH recommendations for CRE colonization screening of high-risk individuals. CRE screening of exposed high-risk employees was conducted by the University of Pennsylvania Occupational Health service and PDPH. Human rectal swabs were analyzed at the Antibiotic Resistance Laboratory Network (ARLN) Maryland Laboratory. PDPH were invited to conduct an onsite infection control assessment and to suggest improvements. Results: No pet owners self-identified in high-risk groups to be screened. In total, 10 high-risk staff were screened, and no colonized individuals were detected. Recommendations made by the PDPH to MJRVH included improvement of infection prevention and control policies (eg, consolidation of the infection control manual and identification of lead staff member), improvement in hand hygiene (HH) compliance (eg, increasing amount of HH supplies), improvement of environment of care (eg, decluttering and evaluation of mulched animal relief area), and improvement of respiratory care processes (eg, standardization of care policies). MJRVH made substantial improvements across recommendation areas including revision of infection control manual, creation of a full-time infection preventionist position, individual alcohol hand sanitizers for patient cages, and environmental decluttering and decontamination. PDPH and MJRVH maintained frequent communication about infection control improvements. Conclusions: No positive transmission to high-risk staff members suggest that, like in human healthcare facilities, transmission of CRE to caretakers may not be a common event. Stronger communication and collaboration is required from Departments of Public Health (DPH) to the veterinary profession regarding the reporting requirements of emerging pathogens such as CRE. Veterinary facilities should view DPH as a valuable resource for recommendations to fill in gaps that exist in infection control “best practices,” particularly for novel pathogens in veterinary settings.

Funding: None

Disclosures: Jane M. Gould reports that her spouse receives salary from Incyte.

Background: Biallelic variants in POLR1C are associated with POLR3-related leukodystrophy (POLR3-HLD), or 4H leukodystrophy (Hypomyelination, Hypodontia, Hypogonadotropic Hypogonadism), and Treacher Collins syndrome (TCS). The clinical spectrum of POLR3-HLD caused by variants in this gene has not been described. Methods: A cross-sectional observational study involving 25 centers worldwide was conducted between 2016 and 2018. The clinical, radiologic and molecular features of 23 unreported and previously reported cases of POLR3-HLD caused by POLR1C variants were reviewed. Results: Most participants presented between birth and age 6 years with motor difficulties. Neurological deterioration was seen during childhood, suggesting a more severe phenotype than previously described. The dental, ocular and endocrine features often seen in POLR3-HLD were not invariably present. Five patients (22%) had a combination of hypomyelinating leukodystrophy and abnormal craniofacial development, including one individual with clear TCS features. Several cases did not exhibit all the typical radiologic characteristics of POLR3-HLD. A total of 29 different pathogenic variants in POLR1C were identified, including 13 new disease-causing variants. Conclusions: Based on the largest cohort of patients to date, these results suggest novel characteristics of POLR1C-related disorder, with a spectrum of clinical involvement characterized by hypomyelinating leukodystrophy with or without abnormal craniofacial development reminiscent of TCS.

We propose the concept of the “Fish Revolution” to demarcate the dramatic increase in North Atlantic fisheries after AD 1500, which led to a 15-fold increase of cod (Gadus morhua) catch volumes and likely a tripling of fish protein to the European market. We consider three key questions: (1) What were the environmental parameters of the Fish Revolution? (2) What were the globalising effects of the Fish Revolution? (3) What were the consequences of the Fish Revolution for fishing communities? While these questions would have been considered unknowable a decade or two ago, methodological developments in marine environmental history and historical ecology have moved information about both supply and demand into the realm of the discernible. Although much research remains to be done, we conclude that this was a major event in the history of resource extraction from the sea, mediated by forces of climate change and globalisation, and is likely to provide a fruitful agenda for future multidisciplinary research.

A suite of coarsely crystalline samples of crinoidal limestone adjacent to a PbS-CaF2-CaCO3 vein in the North Pennine orefield (Greenhow Rake) was analysed by three independent methods [Inductively Coupled Plasma emission spectroscopy (ICP), Mass Spectrometry (MS) and Gas Chromatography (GC)], in order to determine the nature and origin of trace elements and volatiles released on heating and thermal decrepitation, to establish whether fluid inclusions from the host limestone differed in composition from those within the vein, and to assess the value of the results obtained for mineral exploration. The ICP method gave reproducible results for Ca, Na and K, and significant values for Pb and Zn. Na and K correlate with H2O levels determined by MS/volumetric analysis, suggesting their coexistence within fluid inclusions. No such correlation was found for Pb and Zn, suggesting that these elements were derived by volatilisation, perhaps from traces of galena and sphalerite. Methane showed no correlation with H2O and a source other than aqueous fluid inclusions is thought probable for this volatile.

The vein calcite showed much lower K/Na fluid ratios (0.05 cf 0.1–0.2), than the limestones. The limestone-hosted fluids occur predominantly in crinoid ossicles and are believed to represent early pre-mineralisation fluids, unrelated to those associated with veining. Combined ICP and MS techniques may be of value in investigating samples where fluid inclusions are too small for microthermometric and optical analysis.

Nahcolite (NaHCO3) is identified and recorded for the first time from an igneous rock. Often associated with it is another carbonate mineral tentatively identified as kalicine (KHCO3), which has not previously been recorded as a primary mineral in any rock. These minerals occur in inclusions in apatite crystals in ijolites and carbonatites, and indicate that both ijolite and carbonatite magma must have been considerably richer in soda and potash than is indicated by the chemical analyses of the rocks. The identification was made by a combination of microchemical, solubility, crystallographic, and optical determinations.

Uranium has been detected in fluid inclusion decrepitates from quartz of several granites of the British Isles and from vein quartz associated with the Hcrcynian granites of SW England using ICP. Material, ejected from the inclusions during decrepitation on heating the sample, is transferred into the plasma for qualitative analysis via a stream of argon. Several other elements have been detected in the decrepitate, of which carbon is of particular interest. It shows a strong positive correlation with U and indicates the importance of C (presumably as carbonate complexes) in the transport of U in hydrothermal systems. Approximate order of magnitude estimates of the average U contents of fluid inclusions from the SW England samples, based on the assumption that U in the decrepitates is principally derived from the fluid inclusions, range from less than one to over a thousand ppm. Fluid inclusions may therefore be important in contributing to the levels of U reported in quartz (0.1 to 10 ppm).

Questions of state formation and public authority have been at the top of the development and political agenda in Nepal since 2006. The post-2006 so-called ‘political transition’ has been characterized by rising ethnic tensions, violence, strikes, and a bewildering kaleidoscope of leaders gaining political leverage, only to be marginalized again. In 2015, the Constitution was finally adopted following the earthquakes and amid violent protests from groups who felt their needs were marginalized in the final version. In this article we are concerned to probe how struggles over different technologies of government help throw into relief the various terrains within which public authority is claimed and contested, and, as a result, help to expose the limits of the state. Using the forestry sector as an ethnographic lens, we argue that there is both a profound failure by the state to provide services and stable governance as well as an ability to reproduce itself and to function in some contexts. It is therefore important to understand public authority during this period as both stable and unstable—and at times, instability is what helps to perpetuate particular imaginaries of the Nepali state.

Carbonatites are enriched in critical raw materials such as the rare-earth elements (REE), niobium, fluorspar and phosphate. A better understanding of their fluid regimes will improve our knowledge of how to target and exploit economic deposits. This study shows that multiple fluid phases penetrated the surrounding fenite aureole during carbonatite emplacement at Chilwa Island, Malawi. The first alkaline fluids formed the main fenite assemblage and later microscopic vein networks contain the minerals of potential economic interest such as pyrochlore in high-grade fenite and rare-earth minerals throughout the aureole. Seventeen samples of fenite rock from the metasomatic aureole around the Chilwa Island carbonatite complex were chosen for study. In addition to the main fenite assemblage of feldspar and aegirine ± arfvedsonite, riebeckite and richterite, the fenite contains micro-mineral assemblages including apatite, ilmenite, rutile, magnetite, zircon, rare-earth minerals and pyrochlore in vein networks. Petrography using a scanning electron microscope in energy-dispersive spectroscopy mode showed that the rare-earth minerals (monazite, bastnäsite and parisite) formed later than the fenite feldspar, aegirine and apatite and provide evidence of REE mobility into all grades of fenite. Fenite apatite has a distinct negative Eu anomaly (determined by laser ablation inductively coupled plasma mass spectrometry) that is rare in carbonatite-associated rocks and interpreted as related to pre-crystallization of plagioclase and co-crystallization with K-feldspar in the fenite. The fenite minerals have consistently higher mid REE/light REE ratios (La/Sm ≈ 1.3 monazite, ≈ 1.9 bastnäsite, ≈ 1.2 parisite) than their counterparts in the carbonatites (La/Sm ≈ 2.5 monazite, ≈ 4.2 bastnäsite, ≈ 3.4 parisite). Quartz in the low- and medium-grade fenite hosts fluid inclusions, typically a few micrometres in diameter, secondary and extremely heterogeneous. Single phase, 2- and 3-phase, single solid and multi solid-bearing examples are present, with 2-phase the most abundant. Calcite, nahcolite, burbankite and baryte were found in the inclusions. Decrepitation of inclusions occurred at ∼200°C before homogenization but melting-temperature data indicate that the inclusions contain relatively pure CO2. A minimum salinity of ∼24 wt.% NaCl equivalent was determined. Among the trace elements in whole-rock analyses, enrichment in Ba, Mo, Nb, Pb, Sr, Th and Y and depletion in Co, Hf and V are common to carbonatite and fenite but enrichment in carbonatitic type elements (Ba, Nb, Sr, Th, Yand REE) generally increases towards the inner parts of the aureole. A schematic model contains multiple fluid events, related to first and second boiling of the magma, accompanying intrusion of the carbonatites at Chilwa Island, each contributing to the mineralogy and chemistry of the fenite. The presence of distinct rare-earth mineral microassemblages in fenite at some distance from carbonatite could be developed as an exploration indicator of REE enrichment.

New simultaneous X-ray and radio observations of the archetypal mode-switching pulsar PSR B0943+10 have been carried out with XMM-Newton and the LOFAR, LWA and Arecibo radio telescopes in November 2014. They allowed us to better constrain the X-ray spectral and variability properties of this pulsar and to detect, for the first time, the X-ray pulsations also during the X-ray-fainter mode. The combined timing and spectral analysis indicates that unpulsed non-thermal emission, likely of magnetospheric origin, and pulsed thermal emission from a small polar cap are present during both radio modes and vary in a correlated way.