Advancing the assessment of pacifier effects with a novel computational method.

BACKGROUND: Numerous studies have demonstrated a high likelihood of malocclusions resulting from non-nutritive sucking. Consequently, quantifying the impact of pacifiers can potentially aid in preventing the development or exacerbation of malocclusions and guide the design of improved performance pacifiers. METHODS: This work proposes and assesses a computational methodology that can effectively gather crucial information and provide more precise data regarding the consequences of non-nutritive pacifier sucking. The computational framework utilized is based on solids4Foam [1, 2], a collection of numerical solvers developed within the OpenFOAM® computational library [3]. The computational model focuses on the palate of a six-month-old baby and incorporates various components such as palate tissues, pacifier and tongue, and considers the negative intraoral pressure generated and the tongue displacement. Different models were tested, each offering varying levels of detail in representing the palate structure. These models range from a simplified approach, with one tissue, to a more intricate representation, involving up to five different tissues, offering a more comprehensive palate model compared to existing literature. RESULTS: The analysis of results involved examining the distribution of stress on the palate surface, as well as the displacement and forces exerted on the dental crowns. By comparing the obtained results, it was possible to evaluate the precision of the approaches previously described in the literature. The findings revealed that the predictions were less accurate when using the simplified model with a single tissue for the palate, which is the most common approach proposed in the literature. In contrast, the results demonstrated that the palate model with the most intricate structure, incorporating five different tissues, yielded distinct outcomes compared to all other combinations. CONCLUSIONS: The computational methodology proposed, employing the most detailed palate model, has demonstrated its effectiveness and necessity in obtaining accurate data on the impact of non-nutritive sucking habits, which are recognized as a primary contributor to the development of dental malocclusions. In the future, this approach could be extended to conduct similar studies encompassing diverse pacifier designs, sizes, and age groups. This would foster the design of innovative pacifiers that mitigate the adverse effects of non-nutritive sucking on orofacial structures.

Oscillations observed in umbra, plage, quiet-Sun and the polarity inversion line of active region 11158 using Helioseismic Magnetic Imager/Solar Dynamics Observatory data.

Using data from the Helioseismic Magnetic Imager, we report on the amplitudes and phase relations of oscillations in quiet-Sun, plage, umbra and the polarity inversion line (PIL) of an active region NOAA#11158. We employ Fourier, wavelet and cross-correlation spectra analysis. Waves with 5 min periods are observed in umbra, PIL and plage with common phase values of ϕ(v, I) = π/2, ϕ(v, Blos) = -(π/2). In addition, ϕ(I, Blos) = π in plage are observed. These phase values are consistent with slow standing or fast standing surface sausage wave modes. The line width variations, and their phase relations with intensity and magnetic oscillations, show different values within the plage and PIL regions, which may offer a way to further differentiate wave mode mechanics. Significant Doppler velocity oscillations are present along the PIL, meaning that plasma motion is perpendicular to the magnetic field lines, a signature of Alvènic waves. A time-distance diagram along a section of the PIL shows Eastward propagating Doppler oscillations converting into magnetic oscillations; the propagation speeds range between 2 and 6 km s-1. Lastly, a 3 min wave is observed in select regions of the umbra in the magnetogram data. This article is part of the Theo Murphy meeting issue 'High-resolution wave dynamics in the lower solar atmosphere'.

Airborne transmission of severe acute respiratory syndrome coronavirus-2 to healthcare workers: a narrative review.

Healthcare workers are at risk of infection during the severe acute respiratory syndrome coronavirus-2 pandemic. International guidance suggests direct droplet transmission is likely and airborne transmission occurs only with aerosol-generating procedures. Recommendations determining infection control measures to ensure healthcare worker safety follow these presumptions. Three mechanisms have been described for the production of smaller sized respiratory particles ('aerosols') that, if inhaled, can deposit in the distal airways. These include: laryngeal activity such as talking and coughing; high velocity gas flow; and cyclical opening and closure of terminal airways. Sneezing and coughing are effective aerosol generators, but all forms of expiration produce particles across a range of sizes. The 5-µm diameter threshold used to differentiate droplet from airborne is an over-simplification of multiple complex, poorly understood biological and physical variables. The evidence defining aerosol-generating procedures comes largely from low-quality case and cohort studies where the exact mode of transmission is unknown as aerosol production was never quantified. We propose that transmission is associated with time in proximity to severe acute respiratory syndrome coronavirus-1 patients with respiratory symptoms, rather than the procedures per se. There is no proven relation between any aerosol-generating procedure with airborne viral content with the exception of bronchoscopy and suctioning. The mechanism for severe acute respiratory syndrome coronavirus-2 transmission is unknown but the evidence suggestive of airborne spread is growing. We speculate that infected patients who cough, have high work of breathing, increased closing capacity and altered respiratory tract lining fluid will be significant producers of pathogenic aerosols. We suggest several aerosol-generating procedures may in fact result in less pathogen aerosolisation than a dyspnoeic and coughing patient. Healthcare workers should appraise the current evidence regarding transmission and apply this to the local infection prevalence. Measures to mitigate airborne transmission should be employed at times of risk. However, the mechanisms and risk factors for transmission are largely unconfirmed. Whilst awaiting robust evidence, a precautionary approach should be considered to assure healthcare worker safety.

Cartilage hair hypoplasia with cutaneous lymphomatoid granulomatosis.

Cartilage-hair hypoplasia (CHH) is an autosomal recessive chondrodysplasia characterized by short-stature, sparse hair and impaired cellular immunity. We describe a young girl who was diagnosed with CHH based on the findings of recurrent infections, short stature with metaphyseal chondrodysplasia, and a confirmed bi-allelic RMRP gene mutation. At 13 years, the patient developed an Epstein-Barr virus (EBV)-driven lymphoproliferative disorder involving the lung, which responded partially to chemotherapy. Simultaneously, she developed multiple indurated plaques involving her face, which had histological findings of granulomatous inflammation and EBV-associated low-grade lymphomatoid granulomatosis. The patient received a matched unrelated peripheral blood stem cell transplant at 15 years of age, and her immunological parameters and skin lesions improved. Lymphomatoid forms of granulomatosis and cutaneous EBV-associated malignancies have not been described previously in CHH. This case highlights the possibility of EBV-associated cutaneous malignancy in CHH.

The Helioseismic and Magnetic Imager (HMI) Vector Magnetic Field Pipeline: Magnetohydrodynamics Simulation Module for the Global Solar Corona.

Time-dependent three-dimensional magnetohydrodynamics (MHD) simulation modules are implemented at the Joint Science Operation Center (JSOC) of the Solar Dynamics Observatory (SDO). The modules regularly produce three-dimensional data of the time-relaxed minimum-energy state of the solar corona using global solar-surface magnetic-field maps created from Helioseismic and Magnetic Imager (HMI) full-disk magnetogram data. With the assumption of a polytropic gas with specific-heat ratio of 1.05, three types of simulation products are currently generated: i) simulation data with medium spatial resolution using the definitive calibrated synoptic map of the magnetic field with a cadence of one Carrington rotation, ii) data with low spatial resolution using the definitive version of the synchronic frame format of the magnetic field, with a cadence of one day, and iii) low-resolution data using near-real-time (NRT) synchronic format of the magnetic field on a daily basis. The MHD data available in the JSOC database are three-dimensional, covering heliocentric distances from 1.025 to 4.975 solar radii, and contain all eight MHD variables: the plasma density, temperature, and three components of motion velocity, and three components of the magnetic field. This article describes details of the MHD simulations as well as the production of the input magnetic-field maps, and details of the products available at the JSOC database interface. To assess the merits and limits of the model, we show the simulated data in early 2011 and compare with the actual coronal features observed by the Atmospheric Imaging Assembly (AIA) and the near-Earth in-situ data.

Change in Nox4 expression is accompanied by changes in myogenic marker expression in differentiating C2C12 myoblasts.

Myoblast differentiation is mediated by a cascade of changes in gene expression including transcription factors such as myogenin. Subsequent to myoblast differentiation, there is an increase in expression of the transmembrane protein NADPH oxidase (Nox). Nox is one of the primary factors for the generation of reactive oxygen species (ROS) in myogenic (C2C12) cells. Recently, ROS have been shown to be important regulators of several intracellular signaling pathways, and the full extent of their regulatory roles is yet to be discovered. In the present study, qRT PCR analysis demonstrated that Nox4 isoform is primarily expressed in differentiating C2C12 cells and contributes to the generation of ROS in C2C12 myoblast during differentiation. Over-expression and silencing of Nox4 expression during myoblast differentiation was accompanied by a reduction in intracellular ROS concentrations and an alteration in the expression patterns of Myf5, Pax7, MyoD1, and myogenin. This modulation was found to be associated with ERK1/2 phosphorylation. In both over-expression and reduced expression of Nox4, we found significant reductions in ERK1/2 phosphorylation. This indicates that cellular differentiation may be affected by Nox4-mediated endogenous ROS generation. These data suggest a new opportunity to study the temporal expression of Nox4 in the generation of ROS accompanying changes in myogenic differentiation.

Use of intralesional cisplatin to successfully treat distal limb haemangiosarcoma in a foal.

A 4-month old, 200 kg, grey warmblood colt presented for a firm, non painful mass on the distal medial aspect of the left third metatarsus. Excisional biopsy revealed a diagnosis of haemangiosarcoma. Equine haemangiosarcoma is uncommon and only limited reports of successful treatment are available. The prognosis for survival is therefore considered to be poor. After two separate incidences of recurrence with incomplete excision of the tumour, intralesional treatment with cisplatin without excision or debulking was performed on three separate occasions. Intralesional cisplatin injection was performed at monthly intervals for three treatments. Four years post treatment with cisplatin, the horse remained in remission. This case report describes the diagnostic and treatment challenges for successful treatment of a primary haemangiosarcoma on the distal limb of a warmblood foal using intralesional cisplatin chemotherapy.

Implementation of a standards-based anaesthesia record compliant with the health level 7 (HL7) clinical document architecture (CDA).

With the increasing use of anaesthesia information management systems (AIMS) there is the opportunity for different institutions to aggregate and share information both nationally and internationally. Potential uses of such aggregated data include outcomes research, benchmarking and improvement in clinical practice and patient safety. However, these goals can only be achieved if data contained in records from different sources are truly comparable and there is semantic inter-operability. This paper describes the development of a standard terminology for anaesthesia and also a Domain Analysis Model and implementation guide to facilitate a standard representation of AIMS records as extensible markup language documents that are compliant with the Health Level 7 Version 3 clinical document architecture. A representation of vital signs that is compliant with the International Standards Organization 11073 standard is also discussed.

Receptive field organization of the S-potential.

The receptive fields of S-potentials have been studied in carp retinas. The relationship between the stimulus intensity and area of stimulation was examined for each component of three different types of S-potential. It appears that for each component there is full summation over a large portion of the retina, a type of organization different from that found in the ganglion cell.

Genome-wide detection of recurring sites of uniparental disomy in follicular and transformed follicular lymphoma.

Single-nucleotide polymorphism (SNP) array analysis was performed using the 10K GeneChip array on a series of 26 paired follicular lymphoma (FL) and transformed-FL (t-FL) biopsies and the lymphoma cell lines SCI-1, DoHH2 and RL2261. Regions of acquired homozygosity were detected in 43/52 (83%) primary specimens with a mean of 1.7 and 3.0 aberrations in the FL and t-FL, respectively. A notable feature was the occurrence of recurring sites of acquired uniparental disomy (aUDP) on 6p, 9p, 12q and 17p in cell lines and primary samples. Homozygosity of 9p and 17p arose predominantly in t-FL and in three cases rendered the cell homozygous for a pre-existing mutation of either CDKN2A or TP53. These data suggest that mutation precedes mitotic recombination, which leads to the removal of the remaining wild-type allele. In all, 18 cases exhibited abnormalities in both FL and t-FL samples. In 10 cases blocks of homozygosity were detected in FL that were absent in the subsequent t-FL sample. These differences support the notion that FL and t-FL may arise in a proportion of patients by divergence from a common malignant ancestor cell rather than by clonal evolution from an antecedent FL.

Inter-specific parasite competition: mixed infections of Schistosoma mansoni and S. rodhaini in the definitive host.

Competition between parasite species has been predicted to be an important force shaping parasite and host ecology and evolution, although empirical data are often lacking. Using the Mus musculus-Schistosoma mansoni and Schistosoma rodhaini host-parasite systems we characterized mate choice and inter-specific competition between these two schistosome species. Simultaneous infections revealed species-specific mate preferences for both species as well as suggesting mating competition, with male S. rodhaini appearing dominant over male S. mansoni. S. rodhaini homologous pairs were also shown to have increased reproduction per paired female in the presence of a competitor in simultaneous infections. Overall total reproductive success was, however, similar between the two species under conditions of direct competition due to the greater initial infectivity of S. mansoni in comparison to S. rodhaini. Inter-specific competition was also implicated as increased parasite virulence to the host. The potential effects of such interactions on parasite and host ecology and evolution in nature are discussed.

Time and chemotherapy treatment trends in the treatment of elderly patients (age>or=70 years) with non-small cell lung cancer.

AIMS: Palliative chemotherapy in non-small cell lung cancer (NSCLC) has been established since 1995 and little chemotherapy treatment was given to these patients before 1990. This retrospective study investigates the treatment outcome of elderly patients (age>or=70 years) with NSCLC over the past 13 years in a large UK cancer centre. MATERIALS AND METHODS: A comparison of all-cause survival between the time periods 1990-1994, 1995-1999 and 2000-2004 was adjusted for age, gender, stage and performance status. A comparison of survival was also made between three age groups: 70-74, 75-79 and 80+ years. RESULTS: Between 1990 and 2004, 302 patients>or=70 years had NSCLC. There were differences in age and performance status between the time periods. There was no improvement in median survival between the three time periods (P=0.6). There was little difference in outcome between the three age cohorts. CONCLUSIONS: The analysis shows that there has been no significant improvement in survival for elderly patients with advanced lung cancer treated with chemotherapy in the past 13 years.

A limited role for TP53 mutation in the transformation of follicular lymphoma to diffuse large B-cell lymphoma.

The role of TP53 mutation in transformation of follicular lymphoma (FL) to diffuse large B-cell lymphoma (t-FL) was examined in a panel of 91 lymph node biopsies derived from 29 patients pre- and post-transformation. The entire TP53 coding sequence was screened and immunocytochemistry performed to determine expression of p53 and its key regulator MDM2. A total of 10 mutations were detected in eight patients (28%), although none were present at FL diagnosis. Mutations were not detected solely at the time of transformation; in three patients, mutated TP53 arose in at least one antecedent FL sample (6 months, 2.5 years and 4 years prior to transformation). Loss of heterozygosity at the TP53 locus occurred in 2/20 informative patients (only in t-FL samples). p53 staining was positive in 82% (9/11) of available biopsies with a missense mutation, and negative in 71% (45/63) with wtTP53. MDM2 expression was significantly higher in t-FL samples (mean 72% positive; 95% confidence interval (95% CI) 68-76%) than FL (mean 58% positive; 95% CI 54-62%) (P<0.001) but did not correlate with TP53 status. TP53 mutation has only a limited role in the transformation of FL, exerting a heterogeneous influence upon phenotypic change. In contrast, dysregulation of MDM2 is frequent and may provide a more rational therapeutic target..

Methyl Anthranilate as a Repellent for Western Corn Rootworm Larvae (Coleoptera: Chrysomelidae).

Methyl anthranilate was identified as the active compound in extracts of maize (Zea mays L.) roots that were shown to be repellent to neonate western corn rootworm (Diabrotica virgifera virgifera LeConte) larvae. A bioassay-driven approach was used to isolate the active material from diethyl ether extracts of roots from germinating maize seeds. Separation of the extract on a Florisil column yielded an active fraction of 90:10 hexane:diethyl ether. Analysis with gas chromatography-mass spectrometry identified two compounds in the active fraction: indole (2,3-benzopyrrole) and methyl anthranilate (methyl 2-aminobenzoate). When tested in behavioral bioassays, methyl anthranilate elicited a significant (P < 0.05) repellent response at doses of 1, 10, and 100 µg. In subsequent single-choice bioassays, 1, 10, and 100 µg of methyl anthranilate prevented larvae from approaching 10 mmol/mol concentrations of carbon dioxide, which is normally highly attractive to the larvae. Indole, the other compound identified from the active fraction, did not elicit a behavioral response by the larvae. Methyl anthranilate has potential for development as a management tool for western corn rootworm larvae and may be best suited for use in a push-pull control strategy.

Prenatal therapy in transient abnormal myelopoiesis: a systematic review.

OBJECTIVE: To systematically review current evidence regarding prenatal diagnosis and management of transient abnormal myelopoiesis (TAM) in fetuses with trisomy 21. A novel case of GATA1-positive TAM, in which following serial in utero blood transfusion clinical improvement and postnatal remission were observed, is included. SEARCH STRATEGY AND DATA COLLECTION: A systematic search of electronic databases (inception to October 2014) and reference lists, hand-searching of journals and expert contact. All confirmed cases of prenatal TAM were included for analysis. Data on study characteristics, design and quality were obtained. RESULTS: Of 73 potentially relevant citations identified, 22 studies were included, describing 39 fetuses. All studies included comprised single case or small cohort studies; overall quality was 'very low'. Fetal/neonatal outcome was poor; 12 stillbirths (30.8%), 4 neonatal deaths (10.2%) and 7 infant deaths (17.9%). In two cases, the pregnancy was terminated (5.1%). TAM was primarily detected in the third trimester (79.4%), and in 14 a retrospective diagnosis was made postpartum. Ultrasound features indicative of TAM included hepatomegaly±splenomegaly (79.5%), hydrops fetalis (30.8%), pericardial effusion (23.1%) and aberrant liquor volume (15.4%). When performed, liver function tests were abnormal in 91.6% of cases. CONCLUSIONS: Prenatal TAM presents a challenging diagnosis, and prognosis is poor, with consistently high mortality. A low threshold to measure haematological and biochemical markers is advised when clinical features typical of TAM are detected in the context of trisomy 21. Larger prospective studies are warranted to accurately ascertain the role of GATA1 analysis and potential value of prenatal therapy.

Positionally selective growth of embryonic spinal cord neurites on muscle membranes.

Motor neurons from distinct positions along the rostrocaudal axis generally innervate muscles or muscle fibers from corresponding axial levels. These topographic maps of connectivity are partially restored after denervation or transplantation under conditions in which factors of timing and proximity are eliminated. It is therefore likely that motor neurons and some intramuscular structures bear cues that bias synapse formation in favor of positionally matched partners. To localize these cues, we studied outgrowth of neurites from embryonic spinal cord explants on carpets of membranes isolated from perinatal rat muscles. Neurites from rostral (cervical) and caudal (lumbar) spinal cord slices exhibit distinct growth preferences. In many instances, rostrally derived neurites grew selectively on membranes from forelimb muscles or from a single thoracic muscle (the serratus anterior) when given a choice between these membranes and membranes from hindlimb muscles or laminin. Caudally derived neurites almost never exhibited such rostral preferences, but instead preferred membranes from hindlimb muscles or a single hindlimb muscle (the gluteus) to rostral muscles or laminin. Likewise, spinal neurites exhibited distinct position-related preferences for outgrowth on membranes of clonal myogenic cell lines derived from specific rostral and caudal muscles. Taken together these results suggest that the membranes of motor axons and myotubes bear complementary labels that vary with rostrocaudal position and regulate neuromuscular connectivity.

High-dose therapy and autologous stem-cell support for chemosensitive transformed low-grade follicular non-Hodgkin's lymphoma: a case-matched study from the European Bone Marrow Transplant Registry.

PURPOSE: To assess the outcome of high-dose therapy with autologous stem-cell support in patients with histologic transformation of low-grade follicular non-Hodgkin's lymphoma (NHL) and identify significant prognostic factors, as well as to compare survival of these patients with that of patients with matched low-grade and de novo high- or intermediate-grade NHL undergoing the same procedure. PATIENTS AND METHODS: Fifty patients with transformed low-grade NHL have been reported to the European Bone Marrow Transplant registry. Outcome from high-dose therapy and significant prognostic factors were analyzed. Their survival was also compared with that of 200 patients with matched low-grade NHL and 200 patients with matched de novo high- or intermediate-grade NHL by a case-matched analysis. RESULTS: The procedure-related death rate among the 50 transformed NHL patients was 18%. Overall survival (OS) and progression-free survival (PFS) rates were 51% and 30% at 5 years, respectively. Median PFS time was 13 months. Raised lactate dehydrogenase levels at transformation (P =.0031) was identified as the only adverse significant predictor of PFS on multivariate analysis. A subgroup of patients with residual chemosensitive disease who attained complete remission after high-dose therapy had the best outcome, with an OS at 5 years of 69%. A comparison with matched patients with low-grade disease and with de novo high- or intermediate-grade lymphoma showed no significant difference in OS (P =.939 and P =.438, respectively). CONCLUSION: Patients with chemosensitive transformed lymphoma should be seriously considered for high-dose therapy and autologous stem-cell support.

Duration of chemotherapy in advanced non-small-cell lung cancer: a randomized trial of three versus six courses of mitomycin, vinblastine, and cisplatin.

PURPOSE: So far there are no published data on optimal duration of chemotherapy for advanced non-small-cell lung cancer (NSCLC); six or more courses are usually recommended. We have carried out a multicenter randomized trial comparing three versus six courses of chemotherapy. PATIENTS AND METHODS: Patients with stage IIIb or IV NSCLC were randomized at start of treatment to receive either three or six courses of mitomycin 8 mg/m(2) (courses 1, 2, 4, and 6), vinblastine 6 mg/m(2), and cisplatin 50 mg/m(2) (MVP) every 21 days. Treatment was stopped early in both arms for progressive disease or unacceptable toxicity. Key end points were overall survival, duration of symptom relief, and quality-of-life assessment using the European Organization for Research and Treatment of Cancer (EORTC) core questionnaire QLQ-C30 with lung cancer-specific module QLQ-LC13. RESULTS: Three hundred eight patients were randomized. Seventy-two percent of the 155 patients randomized to three courses completed treatment. In the 153 patients randomized to six courses, 73% completed three courses and 31% six courses. Median survival was 6 versus 7 months, respectively, and 1-year survival 22% versus 25% (P =.2). Median duration of symptom relief was 4.5 months (both arms), and 8% versus 18% had continuing symptom relief (P =.4). Quality-of-life parameters were the same or improved for patients randomized to only three courses, including significantly decreased fatigue (P =.03) and a trend toward decreased nausea and vomiting (P =.06). CONCLUSION: Our findings show no evidence for additional clinical benefit by continuing MVP chemotherapy beyond three courses. This challenges current orthodoxy of six courses or more. Further trials addressing duration of chemotherapy are now warranted, particularly with newer chemotherapy schedules.

Role of image-guided core-needle biopsy in the management of patients with lymphoma.

PURPOSE: The results of 106 radiologically guided core needle biopsies in 96 patients were analyzed retrospectively to evaluate the accuracy, safety, and role of this technique in the management of patients with lymphoma and to determine factors predictive of success. PATIENTS AND METHODS: Biopsies were performed in 51 patients with low-grade non-Hodgkin's lymphoma (NHL), 24 with high-grade NHL, 16 with previously diagnosed Hodgkin's disease (HD), and 15 with no previous history of lymphoma. Disease was infradiaphragmatic in 92 patients and supradiaphragmatic in 14. Computed tomography (CT) guidance was used in 98 biopsies and ultrasonography (US) in eight. RESULTS: The biopsy was diagnostic and yielded information on the basis of which treatment was started in 88 of 106 patients. The procedure was well tolerated and there were no major complications. Small size of the sample or inappropriate tissue sampled were the main causes of failure. The technique was equally successful in the diagnosis of HD and both high-grade and low-grade NHL as in nonlymphoproliferative disorders. The procedure was equally successful at diagnosis as at suspected recurrence or progression. In 33 of 80 cases in which the biopsy was performed at the time of recurrence or progression, the histology had changed; in 31 of 33, this influenced treatment. The technique was efficient at diagnosing transformation of follicular NHL in 16 of 18 patients, which allowed early adjustment of treatment at recurrence. CONCLUSION: At St Bartholomew's Hospital (SBH), image-guided core-needle biopsy has proven to be a quick, safe, and efficient alternative to excisional biopsy in the evaluation of lymphoproliferative disorders at presentation, recurrence, or progression. It should become the procedure of choice for histologic sampling in the absence of peripheral lymphadenopathy.