Carcinosarcoma of the Rectum: Report of a Rare Colorectal Malignancy and Review of the Literature

Carcinosarcoma (CS) is a rare mixed mesodermal malignancy most commonly affecting the female reproductive organs, respiratory tract, head, and neck. Though infrequent, it may affect the gastrointestinal tract, most often the oesophagus and only very rarely the rectum. Histologically, it is composed of two distinct elements of epithelial and mesenchymal origin. Clinically, it is a very aggressive tumour with many patients presenting with metastatic lymph nodes or distant metastases at the time of diagnosis. Prognosis is poor despite intervention with the majority of patients dying within six months. Due to the rarity of this condition, there are no specific treatment guidelines presently available. We describe the case of an 80-year-old patient with carcinosarcoma of the rectum with discussion of the immunohistochemistry and review the available literature pertaining to this rare presentation

Come back Marshall, all is forgiven? : Complexity, evolution, mathematics and Marshallian exceptionalism

Marshall was the great synthesiser of neoclassical economics. Yet with his qualified assumption of self-interest, his emphasis on variation in economic evolution and his cautious attitude to the use of mathematics, Marshall differs fundamentally from other leading neoclassical contemporaries. Metaphors inspire more specific analogies and ontological assumptions, and Marshall used the guiding metaphor of Spencerian evolution. But unfortunately, the further development of a Marshallian evolutionary approach was undermined in part by theoretical problems within Spencer's theory. Yet some things can be salvaged from the Marshallian evolutionary vision. They may even be placed in a more viable Darwinian framework.Peer reviewedFinal Accepted Versio

Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development.

BACKGROUND: We present the genome sequence of the tammar wallaby, Macropus eugenii, which is a member of the kangaroo family and the first representative of the iconic hopping mammals that symbolize Australia to be sequenced. The tammar has many unusual biological characteristics, including the longest period of embryonic diapause of any mammal, extremely synchronized seasonal breeding and prolonged and sophisticated lactation within a well-defined pouch. Like other marsupials, it gives birth to highly altricial young, and has a small number of very large chromosomes, making it a valuable model for genomics, reproduction and development. RESULTS: The genome has been sequenced to 2 × coverage using Sanger sequencing, enhanced with additional next generation sequencing and the integration of extensive physical and linkage maps to build the genome assembly. We also sequenced the tammar transcriptome across many tissues and developmental time points. Our analyses of these data shed light on mammalian reproduction, development and genome evolution: there is innovation in reproductive and lactational genes, rapid evolution of germ cell genes, and incomplete, locus-specific X inactivation. We also observe novel retrotransposons and a highly rearranged major histocompatibility complex, with many class I genes located outside the complex. Novel microRNAs in the tammar HOX clusters uncover new potential mammalian HOX regulatory elements. CONCLUSIONS: Analyses of these resources enhance our understanding of marsupial gene evolution, identify marsupial-specific conserved non-coding elements and critical genes across a range of biological systems, including reproduction, development and immunity, and provide new insight into marsupial and mammalian biology and genome evolution

The Dust Properties of Two Hot R Coronae Borealis Stars and a Wolf-Rayet Central Star of a Planetary Nebula: in Search of a Possible Link

We present new Spitzer/IRS spectra of two hot R Coronae Borealis (RCB) stars, one in the Galaxy,V348 Sgr, and one lying in the LMC, HV 2671. These two objects may constitute a link between the RCB stars and the late Wolf-Rayet ([WCL]) class of central stars of planetary nebula (CSPNe) such as CPD -56 8032 that has little or no hydrogen in their atmospheres. HV 2671 and V348 Sgr are members of a rare subclass that has significantly higher effective temperatures than most RCB stars, but sharing the traits of hydrogen deficiency and dust formation that define the cooler RCB stars. The [WC] CSPNe star, CPD -56 8032, displays evidence for dual-dust chemistry showing both PAHs and crystalline silicates in its mid-IR spectrum. HV 2671 shows strong PAH emission but shows no sign of having crystalline silicates. The spectrum of V348 Sgr is very different from those of CPD -56 8032 and HV 2671. The PAH emission seen strongly in the other two stars is not present. Instead, the spectrum is dominated by a broad emission centered at about 8.2 micron. The mid-IR spectrum of CPD -56 8032 shows emission features that may be associated with C60. The other two stars do not show evidence for C60. HV 2671 has also been detected by Herschel/PACS and SPIRE. V348 Sgr and CPD -56 8032 have been detected by AKARI/FIS. These data were combined with Spitzer, IRAS, 2MASS and other photometry to produce their spectral energy distributions from the visible to the far-IR. Monte Carlo radiative transfer modeling was used to study the circumstellar dust around these stars. HV 2671 and CPD -56 8032 require both a flared inner disk with warm dust and an extended diffuse envelope with cold dust to to fit their SEDs. The SED of V348 Sgr can be fit with a much smaller disk and envelope.Comment: 20 pages, 5 figures, accepted for publication in The Astronomical Journa

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

Carcinosarcoma of the Rectum: Report of a Rare Colorectal Malignancy and Review of the Literature

Carcinosarcoma (CS) is a rare mixed mesodermal malignancy most commonly affecting the female reproductive organs, respiratory tract, head, and neck. Though infrequent, it may affect the gastrointestinal tract, most often the oesophagus and only very rarely the rectum. Histologically, it is composed of two distinct elements of epithelial and mesenchymal origin. Clinically, it is a very aggressive tumour with many patients presenting with metastatic lymph nodes or distant metastases at the time of diagnosis. Prognosis is poor despite intervention with the majority of patients dying within six months. Due to the rarity of this condition, there are no specific treatment guidelines presently available. We describe the case of an 80-year-old patient with carcinosarcoma of the rectum with discussion of the immunohistochemistry and review the available literature pertaining to this rare presentation

Carcinosarcoma of the Rectum: Report of a Rare Colorectal Malignancy and Review of the Literature

Carcinosarcoma (CS) is a rare mixed mesodermal malignancy most commonly affecting the female reproductive organs, respiratory tract, head, and neck. Though infrequent, it may affect the gastrointestinal tract, most often the oesophagus and only very rarely the rectum. Histologically, it is composed of two distinct elements of epithelial and mesenchymal origin. Clinically, it is a very aggressive tumour with many patients presenting with metastatic lymph nodes or distant metastases at the time of diagnosis. Prognosis is poor despite intervention with the majority of patients dying within six months. Due to the rarity of this condition, there are no specific treatment guidelines presently available. We describe the case of an 80-year-old patient with carcinosarcoma of the rectum with discussion of the immunohistochemistry and review the available literature pertaining to this rare presentation

Quality of health literacy instruments used in children and adolescents:a systematic review

Objective: Improving health literacy at an early age is crucial to personal health and development. Although health literacy in children and adolescents has gained momentum in the past decade, it remains an under-researched area, particularly health literacy measurement. This study aimed to examine the quality of health literacy instruments used in children and adolescents and to identify the best instrument for field use. Design: Systematic review. Setting: A wide range of settings including schools, clinics and communities. Participants: Children and/or adolescents aged 6–24 years. Primary and secondary outcome measures: Measurement properties (reliability, validity and responsiveness) and other important characteristics (eg, health topics, components or scoring systems) of health literacy instruments. Results: There were 29 health literacy instruments identified from the screening process. When measuring health literacy in children and adolescents, researchers mainly focus on the functional domain (basic skills in reading and writing) and consider participant characteristics of developmental change (of cognitive ability), dependency (on parents) and demographic patterns (eg, racial/ethnic backgrounds), less on differential epidemiology (of health and illness). The methodological quality of included studies as assessed via measurement properties varied from poor to excellent. More than half (62.9%) of measurement properties were unknown, due to either poor methodological quality of included studies or a lack of reporting or assessment. The 8-item Health Literacy Assessment Tool (HLAT-8) showed best evidence on construct validity, and the Health Literacy Measure for Adolescents showed best evidence on reliability. Conclusions: More rigorous and high-quality studies are needed to fill the knowledge gap in measurement properties of health literacy instruments. Although it is challenging to draw a robust conclusion about which instrument is the most reliable and the most valid, this review provides important evidence that supports the use of the HLAT-8 to measure childhood and adolescent health literacy in future school-based research.Published versio