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We investigated the effects of maternal vitamin and mineral supplementation throughout gestation on gene expression in the jejunal mucosa of neonatal calves. Crossbred Angus heifers (n = 14) were estrus synchronized, bred to female-sexed semen, and randomly assigned to a basal diet (Control, CON; n = 7) or the basal diet plus vitamin and mineral supplement (Treatment, VTM; n = 7). After parturition, calves were removed from their dams before suckling, fed colostrum replacer, and euthanized 30 h after the first feeding. A subsample of the mucosa of the mid-jejunum was collected, and total RNA was isolated. Gene expression was measured using RNA-Seq, and differentially expressed genes (DEGs) were identified using DESeq2. We identified 528 DEGs from the jejunal mucosa between the VTM and CON calves (P ≤ 0.05 and |log2FC| ≥ 0.5). The DEGs were associated with nutrient transport, lipid metabolism, and immune-related biological processes and pathways. Interestingly, genes underlying the complement and coagulation cascades were mostly downregulated in calves born to VTM dams. On the other hand, the cytokine-cytokine receptor interaction KEGG pathway showed most genes upregulated (LIFR, KDR, TNFRSF4, TNFSF18, FLT1, and TNFRSF12A). Our results show that vitamin and mineral supplementation throughout gestation affects genes underlying tissue structure, nutrient transport and metabolism, and immune system pathways in neonates. The implications of such changes and the long-term outcomes on herd health and performance warrant further research.
The impact of required durations of therapy for antibiotic orders at the time of order entry has not been reported. Requiring ordering clinicians to enter stop dates at the time of antibiotic order entry decreased DOT/1000 patient days for orders with empiric indication from 154 to 119 (–34.9 (–55.7 to –14)).
Sensory-motor decoupling at the cortical level involving cholinergic circuitry has also been reported in Parkinson’s Disease (PD). Short-latency afferent inhibition (SAI) is a transcranial magnetic stimulation (TMS) paradigm that has been used previously to probe cortical cholinergic circuits in well-characterised subgroups of patients with PD. In the current study, we compared SAI in a cohort of PD patients at various stages of disease and explored correlations between SAI and various clinical measures of disease severity.
Methods:
The modified Hoehn and Yahr (H&Y) scale was used to stage disease in 22 patients with PD. Motor and cognitive function were assessed using the MDS-UPDRS (Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale) part III and MoCA (Montreal Cognitive Assessment) score, respectively. Objective gait assessment was performed using an electronic walkway (GAITRite®). SAI was measured as the average percentage inhibition of test motor-evoked potentials (MEPs) conditioned by electrical stimulation of the contralateral median nerve at the wrist.
Results:
SAI was significantly reduced in patients with advanced PD (H&Y stage 3) compared to early PD patients (H&Y stage 1) on pairwise comparison. The visuospatial executive function and orientation domains of cognition demonstrated significant negative associations with SAI.
Conclusion:
Cortical sensory-motor integration is progressively diminished as disease progresses. The observation that a reduction in SAI is associated with a reduction in cognitive function possibly reflects the progressive involvement of cortical cholinergic circuits in PD with increasing motor stage. Future longitudinal studies are necessary to confirm this preliminary result.
A supraglacial debris layer controls energy transfer to the ice surface and moderates ice ablation on debris-covered glaciers. Measurements of vertical temperature profiles within the debris enables the estimation of thermal diffusivities and sub-debris ablation rates. We have measured the debris-layer temperature profiles at 16 locations on Satopanth Glacier (central Himalaya) during the ablation seasons of 2016 and 2017. Debris temperature profile data are typically analysed using a finite-difference method, assuming that the debris layer is a homogeneous one-dimensional thermal conductor. We introduce three more methods for analysing such data that approximate the debris layer as either a single or a two-layered conductor. We analyse the performance of all four methods using synthetic experiments and by comparing the estimated ablation rates with in situ glaciological observations. Our analysis shows that the temperature measurements obtained at equispaced sensors and analysed with a two-layered model improve the accuracy of the estimated thermal diffusivity and sub-debris ablation rate. The accuracy of the ablation rate estimates is comparable to that of the in situ observations. We argue that measuring the temperature profile is a convenient and reliable method to estimate seasonal to sub-seasonal variations of ablation rates in the thickly debris-covered parts of glaciers.
Young people with social disability and severe and complex mental health problems have poor outcomes, frequently struggling with treatment access and engagement. Outcomes may be improved by enhancing care and providing targeted psychological or psychosocial intervention.
Aims
We aimed to test the hypothesis that adding social recovery therapy (SRT) to enhanced standard care (ESC) would improve social recovery compared with ESC alone.
Method
A pragmatic, assessor-masked, randomised controlled trial (PRODIGY: ISRCTN47998710) was conducted in three UK centres. Participants (n = 270) were aged 16–25 years, with persistent social disability, defined as under 30 hours of structured activity per week, social impairment for at least 6 months and severe and complex mental health problems. Participants were randomised to ESC alone or SRT plus ESC. SRT was an individual psychosocial therapy delivered over 9 months. The primary outcome was time spent in structured activity 15 months post-randomisation.
Results
We randomised 132 participants to SRT plus ESC and 138 to ESC alone. Mean weekly hours in structured activity at 15 months increased by 11.1 h for SRT plus ESC (mean 22.4, s.d. = 21.4) and 16.6 h for ESC alone (mean 27.7, s.d. = 26.5). There was no significant difference between arms; treatment effect was −4.44 (95% CI −10.19 to 1.31, P = 0.13). Missingness was consistently greater in the ESC alone arm.
Conclusions
We found no evidence for the superiority of SRT as an adjunct to ESC. Participants in both arms made large, clinically significant improvements on all outcomes. When providing comprehensive evidence-based standard care, there are no additional gains by providing specialised SRT. Optimising standard care to ensure targeted delivery of existing interventions may further improve outcomes.
Cardiac intensivists frequently assess patient readiness to wean off mechanical ventilation with an extubation readiness trial despite it being no more effective than clinician judgement alone. We evaluated the utility of high-frequency physiologic data and machine learning for improving the prediction of extubation failure in children with cardiovascular disease.
Methods:
This was a retrospective analysis of clinical registry data and streamed physiologic extubation readiness trial data from one paediatric cardiac ICU (12/2016-3/2018). We analysed patients’ final extubation readiness trial. Machine learning methods (classification and regression tree, Boosting, Random Forest) were performed using clinical/demographic data, physiologic data, and both datasets. Extubation failure was defined as reintubation within 48 hrs. Classifier performance was assessed on prediction accuracy and area under the receiver operating characteristic curve.
Results:
Of 178 episodes, 11.2% (N = 20) failed extubation. Using clinical/demographic data, our machine learning methods identified variables such as age, weight, height, and ventilation duration as being important in predicting extubation failure. Best classifier performance with this data was Boosting (prediction accuracy: 0.88; area under the receiver operating characteristic curve: 0.74). Using physiologic data, our machine learning methods found oxygen saturation extremes and descriptors of dynamic compliance, central venous pressure, and heart/respiratory rate to be of importance. The best classifier in this setting was Random Forest (prediction accuracy: 0.89; area under the receiver operating characteristic curve: 0.75). Combining both datasets produced classifiers highlighting the importance of physiologic variables in determining extubation failure, though predictive performance was not improved.
Conclusion:
Physiologic variables not routinely scrutinised during extubation readiness trials were identified as potential extubation failure predictors. Larger analyses are necessary to investigate whether these markers can improve clinical decision-making.
The cosmic evolution of the chemical elements from the Big Bang to the present time is driven by nuclear fusion reactions inside stars and stellar explosions. A cycle of matter recurrently re-processes metal-enriched stellar ejecta into the next generation of stars. The study of cosmic nucleosynthesis and this matter cycle requires the understanding of the physics of nuclear reactions, of the conditions at which the nuclear reactions are activated inside the stars and stellar explosions, of the stellar ejection mechanisms through winds and explosions, and of the transport of the ejecta towards the next cycle, from hot plasma to cold, star-forming gas. Due to the long timescales of stellar evolution, and because of the infrequent occurrence of stellar explosions, observational studies are challenging, as they have biases in time and space as well as different sensitivities related to the various astronomical methods. Here, we describe in detail the astrophysical and nuclear-physical processes involved in creating two radioactive isotopes useful in such studies, $^{26}\mathrm{Al}$ and $^{60}\mathrm{Fe}$. Due to their radioactive lifetime of the order of a million years, these isotopes are suitable to characterise simultaneously the processes of nuclear fusion reactions and of interstellar transport. We describe and discuss the nuclear reactions involved in the production and destruction of $^{26}\mathrm{Al}$ and $^{60}\mathrm{Fe}$, the key characteristics of the stellar sites of their nucleosynthesis and their interstellar journey after ejection from the nucleosynthesis sites. This allows us to connect the theoretical astrophysical aspects to the variety of astronomical messengers presented here, from stardust and cosmic-ray composition measurements, through observation of $\gamma$ rays produced by radioactivity, to material deposited in deep-sea ocean crusts and to the inferred composition of the first solids that have formed in the Solar System. We show that considering measurements of the isotopic ratio of $^{26}\mathrm{Al}$ to $^{60}\mathrm{Fe}$ eliminate some of the unknowns when interpreting astronomical results, and discuss the lessons learned from these two isotopes on cosmic chemical evolution. This review paper has emerged from an ISSI-BJ Team project in 2017–2019, bringing together nuclear physicists, astronomers, and astrophysicists in this inter-disciplinary discussion.
In November 2017, eight confirmed measles cases were reported to Public Health England from a hospital in the West Midlands. A multidisciplinary Incident Management Team (IMT) was established to determine the extent of the problem and coordinate an outbreak response. Between 1 November 2017 and 4 June 2018, a total of 116 confirmed and 21 likely measles cases were linked to this outbreak; just under half (43%) were aged over 15 years of age. Fifty-five of the confirmed cases were hospitalised (48%) and no deaths were reported. At the start of the outbreak, cases were mostly individuals of Romanian origin; the outbreak subsequently spread to the wider population. Over the 8-month response, the IMT conducted the following control measures: extensive contact tracing, immediate provision of post-exposure prophylaxis, community engagement amongst specific high-risk groups, MMR awareness raising including catch-up campaigns and enhanced vaccination services at selected GP surgeries. Key challenges to the effective control measures included language difficulties limiting community engagement; delays in diagnosis, notification and appropriate isolation of cases; limited resources for contact tracing across multiple high-risk settings (including GPs and hospitals) and lack of timely data on vaccine coverage in sub-groups of the population to guide public health action.
Through diversity of composition, sequence, and interfacial structure, hybrid materials greatly expand the palette of materials available to access novel functionality. The NSF Division of Materials Research recently supported a workshop (October 17–18, 2019) aiming to (1) identify fundamental questions and potential solutions common to multiple disciplines within the hybrid materials community; (2) initiate interfield collaborations between hybrid materials researchers; and (3) raise awareness in the wider community about experimental toolsets, simulation capabilities, and shared facilities that can accelerate this research. This article reports on the outcomes of the workshop as a basis for cross-community discussion. The interdisciplinary challenges and opportunities are presented, and followed with a discussion of current areas of progress in subdisciplines including hybrid synthesis, functional surfaces, and functional interfaces.
Introduction: Vaginal bleeding in early pregnancy is a common emergency department (ED) presentation, with many of these episodes resulting in poor obstetrical outcome. These outcomes have been extensively studied, but there have been few evaluations of what variables are associated predictors. This study aimed to identify predictors of less than optimal obstetrical outcomes for women who present to the ED with early pregnancy bleeding. Methods: A regional centre health records review included pregnant females who presented to the ED with vaginal bleeding at <20 weeks gestation. This study investigated differences in presenting features between groups with subsequent optimal outcomes (OO; defined as a full-term live birth >37 weeks) and less than optimal outcomes (LOO; defined as a miscarriage, stillbirth or pre-term live birth). Predictor variables included: maternal age, gestational age at presentation, number of return ED visits, socioeconomic status (SES), gravida-para-abortus status, Rh status, Hgb level and presence of cramping. Rates and results of point of care ultrasound (PoCUS) and ultrasound (US) by radiology were also considered. Results: Records for 422 patients from Jan 2017 to Nov 2018 were screened and 180 patients were included. Overall, 58.3% of study participants had a LOO. The only strong predictor of outcome was seeing an Intra-Uterine Pregnancy (IUP) with Fetal Heart Beat (FHB) on US; OO rate 74.3% (95% CI 59.8-88.7; p < 0.01). Cramping (with bleeding) trended towards a higher rate of LOO (62.7%, 95% CI 54.2-71.1; p = 0.07). SES was not a reliable predictor of LOO, with similar clinical outcome rates above and below the poverty line (57.5% [95% CI 46.7-68.3] vs 59% [95% CI 49.3-68.6] LOO). For anemic patients, the non-live birth rate was 100%, but the number with this variable was small (n = 5). Return visits (58.3%, 95% CI 42.2-74.4), previous abortion (58.8%, 95% CI 49.7-67.8), no living children (60.2%, 95% CI 50.7-69.6) and past pregnancy (55.9%, 95% CI 46.6-65.1) were not associated with higher rates of LOO. Conclusion: Identification of a live IUP, anemia, and cramping have potential as predictors of obstetrical outcome in early pregnancy bleeding. This information may provide better guidance for clinical practice and investigations in the emergency department and the predictive value of these variables support more appropriate counseling to this patient population.
To identify patient and provider characteristics associated with high-volume antibiotic prescribing for children in Tennessee, a state with high antibiotic utilization.
Design:
Cross-sectional, retrospective analysis of pediatric (aged <20 years) outpatient antibiotic prescriptions in Tennessee using the 2016 IQVIA Xponent (formerly QuintilesIMS) database.
Methods:
Patient and provider characteristics, including county of prescription fill, rural versus urban county classification, patient age group, provider type (nurse practitioner, physician assistant, physician, or dentist), physician specialty, and physician years of practice were analyzed.
Results:
Tennessee providers wrote 1,940,011 pediatric outpatient antibiotic prescriptions yielding an antibiotic prescribing rate of 1,165 per 1,000 population, 50% higher than the national pediatric antibiotic prescribing rate. Mean antibiotic prescribing rates varied greatly by county (range, 39–2,482 prescriptions per 1,000 population). Physicians wrote the greatest number of antibiotic prescriptions (1,043,030 prescriptions, 54%) of which 56% were written by general pediatricians. Pediatricians graduating from medical school prior to 2000 were significantly more likely than those graduating after 2000 to be high antibiotic prescribers. Overall, 360 providers (1.7% of the 21,798 total providers in this dataset) were responsible for nearly 25% of both overall and broad-spectrum antibiotic prescriptions; 20% of these providers practiced in a single county.
Conclusions:
Fewer than 2% of providers account for 25% of pediatric antibiotic prescriptions. High antibiotic prescribing for children in Tennessee is associated with specific patient and provider characteristics that can be used to design stewardship interventions targeted to the highest prescribing providers in specific counties and specialties.
Duck production has the potential to play a major role in agricultural economy. Asian countries alone contribute 84.2% of total duck meat produced in the world. Driven by the demand of processed foods among consumers, the global duck meat market is expected to grow at a steady pace, reaching a value of about $11.23 billion in the coming years. Duck meat has higher muscle fibre content in breast meat compared to chicken, and is considered as red meat. Moreover, due to a higher fat content (13.8%) than chicken and a stronger gamey flavour, duck meat can be less appreciated by the consumer. Development and diversification of ready-to-eat duck meat products is expected to increase consumption levels. Hence, the status of duck meat production, physicochemical properties, processing, including traditional products, and development of novel value-added ready-to-eat products from spent duck meat is discussed in detail to explore its importance as an alternative to chicken.
Glaciological ablation is computed from point-scale data at a few ablation stakes that are usually regressed as a function of elevation and averaged over the area-elevation distribution of a glacier. This method is contingent on a tight control of elevation on local ablation. However, in debris-covered glaciers, systematic and random spatial variations of debris thickness modify the ablation rates. We propose and test a method to compute sub-debris ablation where stake data are interpolated as a function of debris-thickness alone and averaged over the debris-thickness distribution at different parts of the glacier. We apply this method on Satopanth Glacier located in Central Himalaya utilising ~1000 ablation measurements obtained from a network of up to 56 stakes during 2015–2017. The estimated mean sub-debris ablation ranges between 1.5±0.2 to 1.7±0.3 cm d−1. We show that the debris-thickness-dependent regression describes the spatial variability of the sub-debris ablation better than the elevation dependent regression. The uncertainties in ablation estimates due to the corresponding uncertainties in the measurement of ablation and debris-thickness distribution, and those due to interpolation procedures are estimated using Monte Carlo methods. Possible biases due to a finite number of stakes used are also investigated.
Frailty is associated with cognitive decline in older adults. However, the mechanisms explaining this relationship are poorly understood. We hypothesized that sleep quality may mediate the relationship between frailty and cognition.
Participants:
154 participants aged between 50-90 years (mean = 69.1 years, SD = 9.2 years) from the McKnight Brain Registry were included.
Measurements:
Participants underwent a full neuropsychological evaluation, frailty and subjective sleep quality assessments. Direct relationships between frailty and cognitive function were assessed using linear regression models. Statistical mediation of these relationships by sleep quality was assessed using nonparametric bootstrapping procedures.
Results:
Frailty severity predicted weaker executive function (B = −2.77, β = −0.30, 95% CI = −4.05 – −1.29) and processing speed (B = −1.57, β = −0.17, 95% CI = −3.10 – −0.16). Poor sleep quality predicted poorer executive function (B = −0.47, β = −0.21, 95% CI = −0.79 – −0.08), processing speed (B = −0.64, β = −0.28, 95% CI = −0.98 – −0.31), learning (B = −0.42, β = −0.19, 95% CI = −0.76 – −0.05) and delayed recall (B = −0.41, β = −0.16, 95% CI = −0.80 – −0.31). Poor sleep quality mediated the relationships between frailty severity and executive function (B = −0.66, β = −0.07, 95% CI = −1.48 – −0.39), learning (B = −0.85, β = −0.07, 95% CI = −1.85 – −0.12), delayed recall (B = −0.47, β = −0.08, 95% CI = −2.12 – −0.39) and processing speed (B = −0.90, β = −0.09, 95% CI = −1.85 – −0.20).
Conclusions:
Relationships between frailty severity and several cognitive outcomes were significantly mediated by poor sleep quality. Interventions to improve sleep quality may be promising avenues to prevent cognitive decline in frail older adults.
A commercially available combined X-ray diffraction – differential scanning calorimetry (XRD-DSC) stage was adapted for studies of gas loading in microporous materials, including metal organic frameworks (MOFs). Insertion of a custom-built humid atmosphere swing chamber (HASC) between a humidity generator and the XRD-DSC stage facilitates both humid atmosphere and vacuum swing gas loading. The HASC is necessary to buffer between the humidity generator and the XRD-DSC stage, allowing the gas mixture to homogenize prior to sample exposure, so that both humid atmosphere and vacuum swings could be performed. The changes in XRD can be used to follow structural changes, including collapse, which is indicative of a lack of microporosity upon activation, and the flexibity of frameworks upon gas sorption–desorption cycles. Measurements of the area under the DSC curve allows for calculation of the isosteric heat of adsorption (Qst; kJ molGAS−1). Vacuum-atmosphere swing experiments performed at different pressure steps allow for the reconstruction of the enthalpy of gas adsorption before and after a phase transition. These modes of operation are illustrated in three case studies from a program of exploratory MOF synthesis used to discover novel materials for selective gas sorption from humid gas streams: (1) gas binding in Stony Brook metal organic framework-1, (2) zeolitic imidazolate framework-7 response to variable pressure vacuum-atmosphere swing, and (3) high throughput evaluation of the selectivity of novel MOFs synthesized from customized linkers.
We observed pediatric S. aureus hospitalizations decreased 36% from 26.3 to 16.8 infections per 1,000 admissions from 2009 to 2016, with methicillin-resistant S. aureus (MRSA) decreasing by 52% and methicillin-susceptible S. aureus decreasing by 17%, among 39 pediatric hospitals. Similar decreases were observed for days of therapy of anti-MRSA antibiotics.
To evaluate the survival outcomes and toxicities experienced by non-metastatic head and neck cancer (HNC) patients receiving modulated radiotherapy (RT).
Materials and methods
A total of 608 HNC patients treated consecutively from March 2010 to December 2014 with common subsites (oral cavity, oropharynx, hypopharynx, larynx and nasopharynx) of HNCs formed the study group. Eligible patients included those treated with radical or postoperative RT between March 2010 and December 2014. More than 90% patients received modulated RT [intensity-modulated radiotherapy (IMRT) or volumetric-modulated arc therapy (VMAT)] with concurrent chemotherapy as per stage guidelines. Demographic parameters and disease-related factors were analysed. Disease-free survival (DFS) was calculated from end date of RT till last follow-up or last date of disease control. Overall survival (OS) was calculated from date of registration to last follow-up date if alive. The primary endpoint was survival. The statistical analyses were performed using SPSS version 20.0 and Kaplan–Meier method was used for calculation survival.
Results
Among the evaluable patients, the median age was 60 years (range: 16–93) with male preponderance (male:female – 513:95). Majority were squamous cell carcinoma 93·4% (568/608). The subsites treated were oral cavity 36·8% (224). oropharynx 26·4% (161), larynx 19·7% (120), hypopharynx 10% (62) and nasopharynx 6·4% (41). RT intent was radical in 63·5% (386) and postoperative in 36·5% (222), with 59·5% (362) receiving concurrent chemotherapy. At last follow-up, 348 (57·2%) patients were alive, 169 (27·7%) patients had succumbed to disease and 120 (24·6%) patients had recurrent disease. Out of 120 recurrent cases loco-regional recurrence, nodal recurrence and distant metastases were seen in 62 (51·7%), 25 (20·8%), 33 (27·5%), respectively. In the entire study cohort at 2 year OS and DFS was 80 and 79% whereas 3 years OS and DFS was 70 and 75%, respectively.
Conclusions
In our study, 2 years and 3 years OS and DFS rates are found comparable to the international data with acceptable toxicity profile with the use of modulated RT. It seems to be possible because of stringent departmental protocols and good medical physics support. Our data re-validates need and benefit of advanced RT techniques like IG-IMRT and VMAT for both postoperative and radical HNC treatment at the cost of minimal long-term side effects. Future stringent follow-up and quality of life issues are being considered in a prospective manner.
The speciation of antimony is strongly influenced by its oxidation state (V, III, 0, —III). Redox processes under anaerobic groundwater conditions may therefore greatly alter the environmental behaviour of Sb. Employing X-ray absorption and photoelectron spectroscopy, we show here that Sb(V) is reduced to Sb(III) by magnetite and mackinawite, two ubiquitous Fe(II)-containing minerals, while Sb(III) is not reduced further. At the surface of magnetite, Sb(III) forms a highly symmetrical sorption complex at the position otherwise occupied by tetrahedral Fe(III). The Sb(V) reduction increases with pH, and at pH values >6.5 Sb(V) is completely reduced to Sb(III) within 30 days. In contrast, at the mackinawite surface, Sb(V) is completely reduced across a wide pH range and within 1 h. The Sb(V) reduction proceeds solely by oxidation of surface Fe(II), while the oxidation state of sulphide is conserved. Independent of whether Sb(V) or Sb(III) was added, an amorphous or nano-particulate SbS3-like solid formed.
Sitathali is an olivine-bronzite chondrite, consisting largely of olivine (Fa18) and orthopyroxene (Fs19) with minor amounts of a clinopyroxene (Ca36Fe12Mg52), plagioclase (An12), nickel-iron, troilite, chromite, and a phosphate (apatite or merrillite). The chemical analysis of a 4 gm sample gave SiO2 39·85, TiO2 0·10, Al2O3 2·84, Cr2O3 0·35, FeO 13·27, MnO 0·28, MgO 23·01, CaO 1·84, Na2O 0·65, K2O 0·15, H2O+ 0·23, H2O− 0·05, P2O5 0·25, FeS 5·09, Fe 10·22, Ni 1·58, Co tr. total 99·76. The metal displays Neumann bands, some deformed, as well as areas of apparent flowage. Troilite locally exhibits twin lamellae and in places replaces kamacite in the plessite fields. Elsewhere it is in braided veinlets and globules, both reflecting former melting. The varied textures suggest a complex post-formational history encompassing several deformational events presumably due to breakups and possible extraterrestrial impacts.