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The Mu2e experiment at the Fermilab Muon Campus will search for the coherent neutrinoless conversion of a muon into an electron in the field of an aluminum nucleus with a sensitivity improvement by a factor of 10000 over existing limits. The Mu2e Trigger and Data Acquisition System (TDAQ) uses otsdaq as the online Data Acquisition System (DAQ) solution. Developed at Fermilab, otsdaq integrates both the artdaq DAQ and the art analysis frameworks for event transfer, filtering, and processing. otsdaq is an online DAQ software suite with a focus on flexibility and scalability and provides a multi-user, web-based, interface accessible through a web browser. The data stream from the detector subsystems is read by a software filter algorithm that selects events which are combined with the data flux coming from a cosmic ray veto system. The Detector Control System (DCS) has been developed using the Experimental Physics and Industrial Control System (EPICS) open source platform for monitoring, controlling, alarming, and archiving. The DCS system has been integrated into otsdaq. A prototype of the TDAQ and the DCS systems has been built at Fermilab's Feynman Computing Center. In this paper, we report on the progress of the integration of this prototype in the online otsdaq software.

Presents a study that developed an algorithm in the C language to reduce leakage in fast Fourier transform algorithm (FFT) measurements. Details on the proposed algorithm; Analysis of errors for the harmonic case; Evaluation of errors for polyharmonic cases.

The International Fusion Materials Irradiation Facility - Demo Oriented NEutron Source (IFMIF-DONES) is a single-sited novel Research Infrastructure for testing, validation and qualification of the materials to be used in a fusion reactor. Recently, IFMIF-DONES has been declared of interest by ESFRI (European Strategy Forum on Research Infrastructures) and its European host city would be Granada (Spain). In spite the first and most important application of IFMIF-DONES related to fusion technology, the unprecedented neutron flux available could be exploited without modifying the routine operation of IFMIF-DONES. Thus, it is already planned an experimental hall for a complementary program with neutrons. Also, a complementary program on the use of the deuteron beam could help IFMIF-DONES to be more sustainable. In the present work, we study radioisotope production with deuterons of 177Lu. The results show the viability of IFMIF-DONES for such production in terms of the needs of a territory of small-medium size. Also the study suggests that new nuclear data at higher deuteron energies are mandatory for an accurate study in this field.

Contempla el Plan Quinquenal, para el desarrollo del cultivo del coco en el país, la determinación de aumentar por lo menos en 2.000 hectáreas las plantaciones de Urabá, zona que tiene una importante producción a todo lo largo de la costa oriental del Golfo de este mismo nombre y que posee todavía una apreciable extensión de terrenos de buena calidad para ampliar dicha producción. Para desarrollar esta iniciativa el Ministerio de la Economía Nacional ha despachado a Urabá más de 80.000 semillas que ya están germinando y adelanta en la actualidad las gestiones necesarias para asegurar la financiación delos pequeños cultivadores de coco.

Calcium and integrin-binding protein 2 (CIB2) and CIB3 bind to transmembrane channel-like 1 (TMC1) and TMC2, the pore-forming subunits of the inner-ear mechano-electrical transduction (MET) apparatus. These interactions have been proposed to be functionally relevant across mechanosensory organs and vertebrate species. Here we show that both CIB2 and CIB3 can form heteromeric complexes with TMC1 and TMC2 and are integral for MET function in mouse cochlea and vestibular end organs as well as in zebrafish inner ear and lateral line. Our AlphaFold 2 models suggest that vertebrate CIB proteins can simultaneously interact with at least two cytoplasmic domains of TMC1 and TMC2 as validated using nuclear magnetic resonance spectroscopy of TMC1 fragments interacting with CIB2 and CIB3. Molecular dynamics simulations of TMC1/2 complexes with CIB2/3 predict that TMCs are structurally stabilized by CIB proteins to form cation channels. Overall, our work demonstrates that intact CIB2/3 and TMC1/2 complexes are integral to hair-cell MET function in vertebrate mechanosensory epithelia.

Autistic people have long been conceptualized from a deficit-based model of disability, but recent self-advocates and scholars have asserted the importance of recognizing autism as both a disability and an important part of a person's social identity. The autistic identity is subject to specific stigma and stressors beyond everyday discrimination and prejudice, which can have many downstream implications on mental health and well-being. Prior research on camouflaging has explained both quantitatively and qualitatively how autistic people conform to norms and mask their autistic traits to better fit in with non-autistic societal standards. Given this paradigm shift in understanding autistic peoples' lived experiences, researchers must also begin to reshape the theories guiding their work in order to improve diagnosis, intervention, and supports. This review examines the extant research on identity-related stigma and camouflaging and their subsequent impacts on mental health outcomes in autism. A model is proposed integrating identity-based theories-specifically the social model of disability, social identity theory, and minority stress model-to explain relationships across research areas and better explain the experiences of autistic people. We discuss how identity-based theories can be applied in autism research to better understand the impacts of stigma and camouflaging on autistic peoples' lived experiences and reduce disparities in their mental health outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Rivera and Bennetto.)

Ternary Portland cement usage with a high amount of cement constituents different from clinker can afford great climate change advantages by lowering the Portland cement clinker content in the final product. This will contribute to cutting greenhouse gas emissions to close to zero by 2050. Such ternary Portland cements can be composed of different amounts of ground granulated blast-furnace slag (GBFS), coal fly ash (CFA), and clinker (K). Cements made with GGBFS, or CFA boast pozzolanic characteristics. Therefore, they would improve both the concrete compressive strength at later ages and durability. The 28- and 90-days mechanical strength test, non-steady state chloride migration test, described in NT BUILD 492, and natural chloride diffusion test (NT BUILD 443) were performed in concrete. Ternary cements made with GBFS and/or CFA presented better chloride diffusion resistance than concrete made with plain Portland cements. Furthermore, the development of compressive strength was delayed. The service life study was developed for concretes made with ternary cements with regard to the chloride penetration case.

RNA-Binding Protein with Multiple Splicing (RBPMS) is a member of family proteins that bind to nascent RNA transcripts and regulate their splicing, localization, and stability. Evidence indicates that RBPMS controls the activity of transcription factors associated with cell growth and proliferation, including AP-1 and Smads. Three major RBPMS protein splice variants (RBPMSA, RBPMSB, and RBPMSC) have been described in the literature. We previously reported that reduced RBPMS levels decreased the sensitivity of ovarian cancer cells to cisplatin treatment. However, little is known about the biological role of the RBPMS splice variants in ovarian cancer cells. We performed RT-PCR and Western blots and observed that both RBPMSA and RBPMSC are reduced at the mRNA and protein levels in cisplatin resistant as compared with cisplatin sensitive ovarian cancer cells. The mRNA and protein levels of RBPMSB were not detectable in any of the ovarian cancer cells tested. To better understand the biological role of each RBPMSA and RBPMSC, we transfected these two splice variants in the A2780CP20 and OVCAR3CIS cisplatin resistant ovarian cancer cells and performed cell proliferation, cell migration, and invasion assays. Compared with control clones, a significant reduction in the number of colonies, colony size, cell migration, and invasion was observed with RBPMSA and RBPMSC overexpressed cells. Moreover, A2780CP20-RBPMSA and A2780CP20-RBPMSC clones showed reduced senescence-associated β-galactosidase (β-Gal)-levels when compared with control clones. A2780CP20-RBPMSA clones were more sensitive to cisplatin treatment as compared with A2780CP20-RBPMSC clones. The A2780CP20-RBPMSA and A2780CP20-RBPMSC clones subcutaneously injected into athymic nude mice formed smaller tumors as compared with A2780CP20-EV control group. Additionally, immunohistochemical analysis showed lower proliferation (Ki67) and angiogenesis (CD31) staining in tissue sections of A2780CP20-RBPMSA and A2780CP20-RBPMSC tumors compared with controls. RNAseq studies revealed many common RNA transcripts altered in A2780CP20-RBPMSA and A2780CP20-RBPMSC clones. Unique RNA transcripts deregulated by each RBPMS variant were also observed. Kaplan-Meier (KM) plotter database information identified clinically relevant RBPMSA and RBPMSC downstream effectors. These studies suggest that increased levels of RBPMSA and RBPMSC reduce cell proliferation in ovarian cancer cells. However, only RBPMSA expression levels were associated with the sensitivity of ovarian cancer cells to cisplatin treatment.

In this community review report, we discuss applications and techniques for fast machine learning (ML) in science-the concept of integrating powerful ML methods into the real-time experimental data processing loop to accelerate scientific discovery. The material for the report builds on two workshops held by the Fast ML for Science community and covers three main areas: applications for fast ML across a number of scientific domains; techniques for training and implementing performant and resource-efficient ML algorithms; and computing architectures, platforms, and technologies for deploying these algorithms. We also present overlapping challenges across the multiple scientific domains where common solutions can be found. This community report is intended to give plenty of examples and inspiration for scientific discovery through integrated and accelerated ML solutions. This is followed by a high-level overview and organization of technical advances, including an abundance of pointers to source material, which can enable these breakthroughs., Competing Interests: MB was employed by the company Xilinx Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor EC is currently organizing a Research Topic with the authors JD, ML, and JN., (Copyright © 2022 Deiana, Tran, Agar, Blott, Di Guglielmo, Duarte, Harris, Hauck, Liu, Neubauer, Ngadiuba, Ogrenci-Memik, Pierini, Aarrestad, Bähr, Becker, Berthold, Bonventre, Müller Bravo, Diefenthaler, Dong, Fritzsche, Gholami, Govorkova, Guo, Hazelwood, Herwig, Khan, Kim, Klijnsma, Liu, Lo, Nguyen, Pezzullo, Rasoulinezhad, Rivera, Scholberg, Selig, Sen, Strukov, Tang, Thais, Unger, Vilalta, von Krosigk, Wang and Warburton.)

Nowadays, cruciate ligament injuries have increased in incidence, since practicing a sport or physical activity has become a trend in current societies. Although this lifestyle generates multiple benefits, as a consequence, injury has also increased. Due to its nature and complexity, the ligaments of the knee are those that are most frequently affected, mainly the ACL (anterior cruciate ligament). This tissue reacts to overexertion or movements out of range, either caused by the exercise itself or caused by trauma caused by the practice of physical activity, causing various degrees of sprain. Whatever the etiology of these injuries, they will require a therapy indicated for each degree of injury. This therapy initially entails immobilization of the affected area and later; physical therapy will be required to a lesser or greater degree. Commonly, in the physiotherapy of these injuries, rehabilitation exercises are prescribed, where the physiotherapist asks a patient to use equipment with an estimated weight. However, the effectiveness of a generalized therapy in this way does not always give the expected results. This is related to the fact that these therapies are standardized and do not consider some factors such as the remaining muscle fibres that are not directly affected by the sprain, which does not mean that they should not be considered. Therefore, in the present work, a biomodel of a human knee has been developed and used to evaluate numerically how the ACL acts under an external load, when there are different degrees of injuries, caused by trauma. Four case studies were considered: Case 1 (control case) where the ACL is healthy, Case 2 where the ACL presents a 1 st -degree sprain, Case 3 where the ACL presents a 2 nd -degree sprain, and finally Case 4 where the ACL presents a 3 rd -sprain grade. After performing the analyses, in the control case, it was found that it presents a balance between tensile and compressive stresses. While in the 4th case, the most critical tensile stress decreases while compression stresses increase. This shows that the ligament, having considerable damage, no longer works as it should and can eventually damage the collateral structures. It was found that, when there was a sprain, where the continuity of the ligament is compromised, a second torsional moment occurs in the ACL which causes the tissue fibres not to act according to their normal physiology or in a healthy state. The results obtained from the present study provide the possibility of predicting where the following injuries will occur by considering the von Mises failure criterion. Likewise, they will allow to improve the therapeutic procedures considering not only the injured structure but also the system as a whole., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2021 Rodrigo Arturo Marquet-Rivera et al.)

Ternary Portland cements are new cementitious materials that contain different amounts of cement replacements. Ternary Portland cements composed of granulated blast-furnace slag (GBFS), coal fly ash (CFA), and clinker (K) can afford some environmental advantages by lowering the Portland cement clinker use. Accordingly, this is an opportunity to reduce carbon dioxide emissions and achieve net-zero carbon emissions by 2050. Furthermore, GBFS and CFA possess pozzolanic properties and enhance the mechanical strength and durability at later ages. Compressive strength and natural carbonation tests were performed in mortar and concrete. Cement-based materials made with GBFS and/or CFA presented a delay in the compressive strength development. In addition, they exhibited lower carbonation resistance than that of mortar and concrete made with plain Portland cements. Concrete reinforcement remains passive in common conditions; however, it could be corroded if the concrete pore solution pH drops due to the carbonation process. Service life estimation was performed for the ternary cements regarding the carbonation process. This information can be useful to material and civil engineers in designing concretes made with these ternary cements.

Crop inoculation with Glomus cubense isolate (INCAM-4, DAOM-241198) promotes yield in banana, cassava, forages, and others. Yield improvements range from 20 to 80% depending on crops, nutrient supply, and edaphoclimatic conditions. However, it is difficult to connect yield effects with G. cubense abundance in roots due to the lack of an adequate methodology to trace this taxon in the field. It is necessary to establish an accurate evaluation framework of its contribution to root colonization separated from native arbuscular mycorrhizal fungi (AMF). A taxon-discriminating primer set was designed based on the ITS nrDNA marker and two molecular approaches were optimized and validated (endpoint PCR and quantitative real-time PCR) to trace and quantify the G. cubense isolate in root and soil samples under greenhouse and environmental conditions. The detection limit and specificity assays were performed by both approaches. Different 18 AMF taxa were used for endpoint PCR specificity assay, showing that primers specifically amplified the INCAM-4 isolate yielding a 370 bp-PCR product. In the greenhouse, Urochloa brizantha plants inoculated with three isolates (Rhizophagus irregularis, R. clarus, and G. cubense) and environmental root and soil samples were successfully traced and quantified by qPCR. The AMF root colonization reached 41-70% and the spore number 4-128 per g of soil. This study demonstrates for the first time the feasibility to trace and quantify the G. cubense isolate using a taxon-discriminating ITS marker in roots and soils. The validated approaches reveal their potential to be used for the quality control of other mycorrhizal inoculants and their relative quantification in agroecosystems.

The modelling of biological structures has allowed great advances in Engineering, Biology, and Medicine. In turn, these advances are seen from the design of footwear and sports accessories, to the design of prostheses, accessories and rehabilitation treatments. The reproduction of the various tissues has gone through an important evolution thanks to the development of computer systems and programs. However, knowledge of the medical-biological and engineering areas continues to be required, and it involves a considerable investment of time and resources. The resulting biomodels still require great precision. The present work shows a methodology that allows to optimize computational resources and reduce elaboration time of biomodels. Through this methodology, it is possible to generate a biomodel of high biofidelity of a human knee. This biomodel is constituted by hard tissues (cortical and trabecular bones) and soft tissues (ligaments and meniscus) resulting in the modelling of the lower third of the femur, the tibial plateaus, the anterior cruciate ligament, posterior cruciate ligament, external lateral ligament, interior lateral ligaments, and the meniscus. With this model and methodology, it is possible to perform numerical analyses that will provide results very similar to those of real life. As, the methodology allows to assign the mechanical properties to each tissue and the anatomical structure., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Rodrigo Arturo Marquet-Rivera et al.)

In the lingual orthodontic technique, there are two paradigms regarding the type of wire used. Regardless of the material or gauge, some orthodontists choose to use the straight wire and resin and bond it to the surface of the tooth; they call it compensations. Other orthodontists prefer to bend the wire, giving it a mushroom shape. There is no specific indication for the use of each type of wire, so orthodontists use them according to their criteria. The present study establishes the bases so that it is possible to find the indications for each type of wire. A clinical trial of a lingual orthodontic patient was used. To carry out the comparative study, a straight arch was placed in his right arch and a mushroom arch in the left arch. Using 3D imaging, a high-biofidelity biomodel of the patient's mandible was generated, with which the FEM analysis was performed, which allowed comparing the reactions of the mandibular bone and appliances with the different arches. It was found that, on the side with the straight arch, there were greater deformations, and in the mushroom arch, there were greater stresses. With this, it is possible to find which clinical cases in each type of wire are indicated., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Rosa Alicia Hernández-Vázquez et al.)

Nuclear β-dystroglycan (β-DG) is involved in the maintenance of nuclear architecture and function. Nonetheless, its relevance in defined nuclear processes remains to be determined. In this study we generated a C2C12 cell-based DG-null model using CRISPR-Cas9 technology to provide insights into the role of β-DG on nuclear processes. Since DG-null cells exhibited decreased levels of lamin B1, we aimed to elucidate the contribution of DG to senescence, owing to the central role of lamin B1 in this pathway. Remarkably, the lack of DG enables C2C12 cells to acquire senescent features, including cell-cycle arrest, increased senescence-associated-β-galactosidase activity, heterochromatin loss, aberrant nuclear morphology and nucleolar disruption. We demonstrated that genomic instability is one driving cause of the senescent phenotype in DG-null cells via the activation of a DNA-damage response associated with mitotic failure, as shown by the presence of multipolar mitotic spindles, which in turn induced the formation of micronuclei and γH2AX foci (DNA-damage marker), telomere shortening and p53/p21 upregulation. Altogether, these events might ultimately lead to premature senescence, impeding the replication of the damaged genome. In summary, we present evidence supporting a role for DG in protecting against senescence, through the maintenance of proper lamin B1 expression/localization and proper mitotic spindle organization.

Experimental research on living beings faces several obstacles, which are more than ethical and moral issues. One of the proposed solutions to these situations is the computational modelling of anatomical structures. The present study shows a methodology for obtaining high-biofidelity biomodels, where a novel imagenological technique is used, which applies several CAM/CAD computer programs that allow a better precision for obtaining a biomodel, with highly accurate morphological specifications of the molar and tissues that shape the biomodel. The biomodel developed is the first lower molar subjected to a basic chewing simulation through the application of the finite element method, resulting in a viable model, able to be subjected to various simulations to analyse molar biomechanical characteristics, as well as pathological conditions to evaluate restorative materials and develop treatment plans. When research is focused in medical and dental investigation aspects, numerical analyses could allow the implementation of several tools commonly used by mechanical engineers to provide new answers to old problems in these areas. With this methodology, it is possible to perform high-fidelity models no matter the size of the anatomical structure, nor the complexity of its structure and internal tissues. So, it can be used in any area of medicine., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Rosa Alicia Hernández-Vázquez et al.)

When it is about restorative dental materials, aesthetics is traditionally preferred. This has led to the selection of materials very visually similar to the enamel, but unfortunately, their mechanical properties are not similar. This often translates into disadvantages than advantages. In the present work, a comparison is made of the stresses that occur during dental occlusion (dental bit) in a healthy dental organ and those that are generated in a dental organ with a dental zirconium restoration. Numerical simulation was carried out by means of the Finite Element Method, in computational biomodels, from Cone-Beam Tomography, to obtain the stresses generated during dental occlusion. It was found that the normal and von Mises stresses generated are substantially greater in the molar with restoration compared to those produced in the healthy molar. In addition, the normal function of the enamel and dentin to disperse these stresses to prevent them from reaching the pulp is altered. Therefore, it is necessary to analyze the indiscriminate use of this restoration material and consider other aspects, in addition to aesthetics and biocompatibility for the choice of restorative materials such as biomechanical compatibility ., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2019 Rosa Alicia Hernández-Vázquez et al.)

The analysis of the distribution of stress in dental organs is a poorly studied area. That is why computational mechanobiological analysis at the tissue level using the finite element method is very useful to achieve a better understanding of the biomechanics and the behaviour of dental tissues in various pathologies. This knowledge will allow better diagnoses, customize treatment plans, and establish the basis for the development of better restoration materials. In the present work, through the use of high-fidelity biomodels, computational mechanobiological analyses were performed on four molar models affected with four different degrees of caries, which are subjected to masticatory forces. With the analyses performed, it is possible to observe that the masticatory forces that act on the enamel are not transmitted to the dentin and to the bone and periodontal ligament to protect the nerve, as it happens in a healthy dental organ. With the presence of decay, these forces are transmitted partly to the pulp. The reactions to the external loads on the dental organs depend on the advances of the carious lesion that they present, since the distribution of stresses is different in a healthy tooth.

The association between the downregulation of genes and DNA methylation in their CpG islands has been extensively studied as a mechanism that favors carcinogenesis. The objective of this study was to analyze the methylation of a set of genes selected based on their microarray expression profiles during the process of hepatocarcinogenesis. Rats were euthanized at: 24 h, 7, 11, 16 and 30 days and 5, 9, 12 and 18 months post-treatment. We evaluated the methylation status in the CpG islands of four deregulated genes (Casp3, Cldn1, Pex11a and Nox4) using methylation-sensitive high-resolution melting technology for the samples obtained from different stages of hepatocarcinogenesis. We did not observe methylation in Casp3, Cldn1 or Pex11a. However, Nox4 exhibited altered methylation patterns, reaching a maximum of 10%, even during the early stages of hepatocarcinogenesis. We observed downregulation of mRNA and protein of Nox4 (97.5% and 40%, respectively) after the first carcinogenic stimulus relative to the untreated samples. Our results suggest that Nox4 downregulation is associated with DNA methylation of the CpG island in its promoter. We propose that methylation is a mechanism that can silence the expression of Nox4, which could contribute to the acquisition of neoplastic characteristics during hepatocarcinogenesis in rats., Competing Interests: The authors declare no competing or financial interests., (© 2017. Published by The Company of Biologists Ltd.)

Intracellular calcium homeostasis in adipocytes is important for the regulation of several functions and is involved in pathological changes in obesity and other associated diseases. Transient Receptor Potential Vanilloid 4 (TRPV4) channels are an important route for calcium entry that operates in a variety of cells and intervenes in a number of functions. In this study, the expression and operation of TRPV4 channels in human cultured adipocytes was evaluated using RT-PCR, Western blotting, the whole-cell patch-clamp technique and fluorescence measurements to characterize these channels and determine intracellular calcium responses. Both the hypoosmolarity and 4alpha-phorbol-didecanoate (4αPDD), a specific TRPV4 agonist, induced a similar HC-067047-sensitive current, which was predominantly inward, and an intracellular Ca(2+) concentration increase, which was exclusively dependent on extracellular calcium, and membrane depolarization. The current had a reverse potential of +31 ± 6 mV and exhibited preferential permeability to Ca(2+) . Insulin, which regulates metabolic homeostasis in adipocytes, attenuated the TRPV4-mediated effects. These results confirm the function of TRPV4 in human cultured adipocytes and its regulation by insulin. J. Cell. Physiol. 231: 954-963, 2016. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Unlabelled: Ovarian ectopic pregnancy is only 3% of all ectopic, with an incidence of 1:7,000-40,000. In the last 10 years, it has been a rise in incidence. Most patients have vaginal bleeding, abdominal pain and shock data. Less than 300-400 cases are reported in the literature., Case: We present the case of a woman with ovarian ectopic pregnancy of 12 weeks of gestation, who have not suggestive clinical signs and whose diagnosis was incidental despite having a regular prenatal ultrasound., Conclusion: Ovarian pregnancy is a rare presentation; diagnosis is difficult and often suggested by clinical data, when clinical data fail, more studies are needed to integrate the diagnosis.

Background: The increasing complexity of medical and surgical care often demands comprehensive preoperative work-ups by medical consultants and detailed management recommendations to optimize the patient's medical ailments before surgery. This article aims to review the available evidence and discuss elements of the preoperative medical consultation that are of particular relevance to surgeons., Methods: The authors performed a comprehensive review of the available medical literature and guidelines pertaining to preoperative medical management and present a narrative summary of their findings., Results: Although many preoperative recommendations are based on expert opinion and consensus, a growing number of studies and clinical practice guidelines provides direction as to what is the best management of patients with medical problems before surgery., Conclusions: Collaborative efforts and adequate communication between the medical and surgical teams are necessary to ensure appropriate patient management before surgery. Although higher-risk patients may require thorough preoperative evaluations, extensive routine investigations may not always be necessary., (Published by Elsevier Inc.)

The most important mutation associated with Multiple Endocrine Neoplasia type 2B (MEN 2B) is the change of thymine to cytosine in codon 918 of exon 16 in the RET oncogene (ATG → ACG). The aim of this work was to develop a single oligoarray by using tandem hybridization to detect the T918C/RET mutation for MEN 2B patients. Two genetically non-related families were studied; each family had a member affected by MEN2B. Both patients presented the T918C/RET mutation in a heterozygous fashion. None of the relatives was positive for this mutation; thus, these cases arose de novo. The proper mutation was confirmed by with different tools, PCR-Fok I endonuclease, direct sequencing, and also using our oligoarray. In this case, it is suitable to use a DNA target smaller than 150 bases with single- or double-stranded DNA and short probes of 7-mer. It was also possible to detect the mutation by employing different sources of DNA, fresh or paraffin-embedded tissues. Therefore, the present oligoarray can identify the most common M918T mutation of RET oncogene from a variety of DNA sources with good specificity and be a good alternative in the molecular diagnosis for MEN 2B cases.

The cardiovascular and haematological effects of purified prothrombin activator derived from the venom of the Australian Common Brown Snake (Pseudonaja textilis) were studied in anaesthetised, mechanically ventilated dogs. Severe depression of systemic blood pressure and cardiac output and a rise in central venous pressure were observed. Thrombocytopenia, prolongation of both prothrombin time and activated partial thromboplastin time and a reduction in serum fibrinogen were also observed. All of these observed effects were prevented by the prior administration of heparin--a naturally occurring anticoagulant. We conclude that the prothrombin activator in Pseudonaja textilis venom may cause cardiovascular depression due to myocardial dysfunction secondary to disseminated intravascular coagulation.

There are many unproven methods of ventilation and oxygenation that have been used in children dying from respiratory failure, including extracorporeal devices and high frequency ventilation. However, no objective predictors of death have been developed that enable clinicians to decide when it is reasonable to use these therapies in children over one month of age with acute respiratory failure. To determine predictors of death, we evaluated the charts of all 42 children aged one month to eighteen years admitted to the intensive care unit who were ventilated for more than twelve hours, received greater than 90% oxygen, received a peak inspiratory pressure greater than 25 cmH2O and had no pre-existing neurodevelopmental handicap. A combination of a variable reflecting ventilation and a variable reflecting oxygenation reliably predicted death: a combination of ventilation index greater than 40 and oxygenation index greater than 0.4 was associated with a 77% chance of mortality (sensitivity 65% and specificity 74%); a combination of peak inspiratory pressure greater than 40 cmH2O and A-aDO2 greater than 580 was associated with an 81% chance of mortality (sensitivity 74% and specificity 79%). These criteria may be useful in predicting death from respiratory failure in children.

Effectiveness of four truncated exponential waveform defibrillators for transchest ventricular defibrillation was evaluated in 27 human-sized animals. With all waveforms, effectiveness was virtually 100% for small subjects, but decreased as body weight increased. These data confirm the electrical dose concept for ventricular defibrillation and demonstrate that the truncated exponential waveform is effective only when adequate current is delivered through the subject's chest.