331 research outputs found

    A Large Nonmetastatic Anaplastic Thyroid Cancer with Complete Thyroidal Confinement

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    Anaplastic thyroid cancer (ATC) is rare but extremely aggressive, which accounts for about 2% of all thyroid cancers yet nearly 50% of thyroid-cancer-associated deaths in the United States. The median survival time from diagnosis is 5 months, with a 1-year survival rate of only 20%. We report here a case of ATC in a 56-year-old man who survived a large ATC. Preoperative fine-needle aspiration biopsy study to a large right thyroid mass suggested ATC. Total thyroidectomy with radical lateral neck and central neck dissection removed a well-circumscribed 9.5 cm tumor without extrathyroidal extension or lymphovascular invasion. All 73 lymph nodes removed were negative for metastasis. The tumor consisted of highly pleomorphic, undifferentiated cells with large zones of necrosis and loss of thyroid transcription factor-1 and thyroglobulin expression. A focal well-differentiated component and PAX8 expression confirmed its thyroid follicular cell origin. Nine months after postsurgical adjuvant concurrent radiation therapy and chemotherapy, the patient remained well without clinical, biochemical, and radiographical evidence for cancer recurrence. This is an unusual case of ATC in that it is one of the largest ATC tumors reported to display mild pathologic behavior and relatively long-term patient survival

    Lymphoepithelial Carcinoma of Salivary Gland EBV-association in Endemic versus Non-Endemic Patients: A Report of 16 Cases

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    Lymphoepithelial carcinoma of salivary glands (LECSG) are rare neoplasms, reported in endemic populations (southeastern Chinese) with a strong Epstein-Barr virus (EBV) association. A retrospective series comparing EBV status within an ethnically diverse population (endemic vs. non-endemic patients) has not been reported. Sixteen LECSG were equally distributed between males (n = 8) and females (n = 8) with a median age of 54 years (range 18 to 85 years) at initial diagnosis. Ten patients were white, 4 Asian, and 2 black. The patients typically presented with swelling or mass for an average of 11.6 months. Tumors affected only major salivary glands: parotid (n = 13); submandibular (n = 3). Tumors were an average of 2.9 cm (range 1.5 to 5.8 cm). Nine of 16 (56%) patients had cervical lymph node metastases at presentation. No patients had nasopharyngeal or oropharyngeal tumors. Microscopically, the tumors were widely infiltrative, characterized by large polygonal to spindled cells arranged in a syncytial, lattice-like network in a background of lymphoplasmacytic cells. The neoplastic cells showed an open-vesicular nuclear chromatin to a more basaloid-morphology, the latter showing hyperchromatic nuclei and less cytoplasm, while nearly all of the cases had associated lymphoepithelial lesions/sialadenitis. By in situ hybridization, 8 of 16 cases had a strong, diffuse EBER expression (4 of 4 Asians; 4 of 12 non-Asians), while with immunohistochemistry all cases tested were pan-cytokeratin, CK5/6 and p63 reactive; none of the cases tested were p16 reactive. All patients were managed with wide or radical excision, 4 with concurrent chemoradiation, and 6 with radiation alone. Distant metastasis (lung, brain, and bone) developed in 2 patients. Overall follow-up (mean 3.8 years) revealed 12 patients alive and 2 dead, none with evidence of disease (mean 4.3 years); one white male alive with disease at 1.9 years, and one Asian female dead of disease at 4.2 years; both of these latter patients had Group IV stage disease. High stage (Group IV) patients had a shorter mean survival than lower stage patients: 3.1 versus 4.8 years, respectively. In conclusion, LECSG are uncommon primary neoplasms. Concurrent lymphoepithelial lesions may help suggest a primary tumor. The tumors, irrespective of race or ethnicity, may express EBER. There is an overall good survival, perhaps better for EBV-negative patients and for those with lower stage disease

    Autonomic modulation in patients with heart failure increases beat-to-beat variability of ventricular action potential duration

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    Background: Exaggerated beat-to-beat variability of ventricular action potential duration (APD) is linked to arrhythmogenesis. Sympathetic stimulation has been shown to increase QT interval variability, but its effect on ventricular APD in humans has not been determined.Methods and Results: Eleven heart failure patients with implanted bi-ventricular pacing devices had activation–recovery intervals (ARI, surrogate for APD) recorded from LV epicardial electrodes under constant RV pacing. Sympathetic activity was increased using a standard autonomic challenge (Valsalva) and baroreceptor indices were applied to determine changes in sympathetic stimulation. Two Valsalvas were performed for each study and were repeated, both off and on bisoprolol. In addition sympathetic nerve activity (SNA) was measured from skin electrodes on the thorax using a novel validated method. Autonomic modulation significantly increased mean short-term variability in ARI; off bisoprolol mean STV increased from 3.73 ± 1.3 to 5.27 ± 1.04 ms (p = 0.01), on bisoprolol mean STV of ARI increased from 4.15 ± 1.14 to 4.62 ± 1 ms (p = 0.14). Adrenergic indices of the Valsalva demonstrated significantly reduced beta-adrenergic function when on bisoprolol (Δ pressure recovery time, p = 0.04; Δ systolic overshoot in Phase IV, p = 0.05). Corresponding increases in SNA from rest both off (1.4 uV, p < 0.01) and on (0.7 uV, p < 0.01) bisoprolol were also seen.Conclusions: Beat-to-beat variability of ventricular APD increases during brief periods of increased sympathetic activity in patients with heart failure. Bisoprolol reduces, but does not eliminate, these effects. This may be important in the genesis of ventricular arrhythmias in heart failure patients

    Developing Classifications of Laryngeal Dysplasia: The Historical Basis

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    During the last 60 years numerous significant attempts have been made to achieve a widely acceptable terminology and histological grading for laryngeal squamous intraepithelial lesions. While dysplasia was included in the pathology of the uterine cervix already in 1953, the term dysplasia was accepted in laryngeal pathology first after the Toronto Centennial Conference on Laryngeal Cancer in 1974. In 1963 Kleinsasser proposed a three-tier classification, and in 1971 Kambic and Lenart proposed a four-tier classification. Since then, four editions of the World Health Organisation (WHO) classification have been proposed (1978, 1991, 2005 and 2017). Several terms such as squamous intraepithelial neoplasia (SIN) and laryngeal intraepithelial neoplasia (LIN) are now being abandoned and replaced by squamous intraepithelial lesions (SIL). The essential change between the 2005 and 2017 WHO classifications is the attempt to induce a simplification from a four- to a two-tier system. The current WHO classification (2017) thus recommends the use of a two-tier system with reasonably clear histopathological criteria for the two groups: low-grade and high-grade dysplasia. Problems with interobserver variability apart, subjectivities and uncertainties remain, but to a lesser degree. Ongoing and additional molecular studies may help to clarify underlying events that will increase our understanding and possibly can facilitate our attempts to obtain an even better classification. The classification needs to be easier for the general pathologist to perform and easier for the clinician to interpret. These two objectives are equally important to provide each patient the best personalised treatment available for squamous intraepithelial lesions.Peer reviewe

    Anomalous relaxation and self-organization in non-equilibrium processes

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    We study thermal relaxation in ordered arrays of coupled nonlinear elements with external driving. We find, that our model exhibits dynamic self-organization manifested in a universal stretched-exponential form of relaxation. We identify two types of self-organization, cooperative and anti-cooperative, which lead to fast and slow relaxation, respectively. We give a qualitative explanation for the behavior of the stretched exponent in different parameter ranges. We emphasize that this is a system exhibiting stretched-exponential relaxation without explicit disorder or frustration.Comment: submitted to PR

    The 2016 Southeastern U.S. Drought: An Extreme Departure From Centennial Wetting and Cooling

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    The fall 2016 drought in the southeastern United States (SE U.S.) appeared exceptional based on its widespread impacts, but the current monitoring framework that only extends from 1979 to present does not readily facilitate evaluation of soil-moisture anomalies in a centennial context. A new method to extend monthly gridded soil-moisture estimates back to 1895 is developed, indicating that since 1895, October–November 2016 soil moisture (0–200 cm) in the SE U.S. was likely the second lowest on record, behind 1954. This severe drought developed rapidly and was brought on by low September–November precipitation and record-high September–November daily maximum temperatures (Tmax). Record-high Tmax drove record-high atmospheric moisture demand, accounting for 28% of the October–November 2016 soil-moisture anomaly. Drought and heat in fall 2016 contrasted with 20th century wetting and cooling in the region but resembled conditions more common from 1895–1956. Dynamically, the exceptional drying in fall 2016 was driven by anomalous ridging over the central United States that reduced south-southwesterly moisture transports into the SE U.S. by approximately 75%. These circulation anomalies were partly promoted by a moderate La Niña and warmth in the tropical Atlantic, but these processes accounted for very little of the SE U.S. drying in fall 2016, implying a large role for internal atmospheric variability. The extended analysis back to 1895 indicates that SE U.S. droughts as strong as the 2016 event are more likely than indicated from a shorter 60 year perspective and continued multidecadal swings in precipitation may combine with future warming to further enhance the likelihood of such events

    Simulation-To-Flight (STF-1): A Mission to Enable CubeSat Software-Based Validation and Verification

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    The Simulation-to-Flight 1 (STF-1) CubeSat mission aims to demonstrate how legacy simulation technologies may be adapted for flexible and effective use on missions using the CubeSat platform. These technologies, named NASA Operational Simulator (NOS), have demonstrated significant value on several missions such as James Webb Space Telescope, Global Precipitation Measurement, Juno, and Deep Space Climate Observatory in the areas of software development, mission operations/training, verification and validation (V&V), test procedure development and software systems check-out. STF-1 will demonstrate a highly portable simulation and test platform that allows seamless transition of mission development artifacts to flight products. This environment will decrease development time of future CubeSat missions by lessening the dependency on hardware resources. In addition, through a partnership between NASA GSFC, the West Virginia Space Grant Consortium and West Virginia University, the STF-1 CubeSat will hosts payloads for three secondary objectives that aim to advance engineering and physical-science research in the areas of navigation systems of small satellites, provide useful data for understanding magnetosphere-ionosphere coupling and space weather, and verify the performance and durability of III-V Nitride-based materials

    Piloting the Global Subsidy: The Impact of Subsidized Artemisinin-Based Combination Therapies Distributed through Private Drug Shops in Rural Tanzania

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    BACKGROUND: WHO estimates that only 3% of fever patients use recommended artemisinin-based combination therapies (ACTs), partly reflecting their high prices in the retail sector from where many patients seek treatment. To overcome this challenge, a global ACT subsidy has been proposed. We tested this proposal through a pilot program in rural Tanzania. METHODS/PRINCIPAL FINDINGS: Three districts were assigned to serve either as a control or to receive the subsidy plus a package of supporting interventions. From October 2007, ACTs were sold at a 90% subsidy through the normal private supply chain to intervention district drug shops. Data were collected at baseline and during intervention using interviews with drug shop customers, retail audits, mystery shoppers, and audits of public and NGO facilities. The proportion of consumers in the intervention districts purchasing ACTs rose from 1% at baseline to 44.2% one year later (p<0.001), and was significantly higher among consumers purchasing for children under 5 than for adults (p = 0.005). No change in ACT usage was observed in the control district. Consumers paid a mean price of $0.58 for ACTs, which did not differ significantly from the price paid for sulphadoxine-pyrimethamine, the most common alternative. Drug shops in population centers were significantly more likely to stock ACTs than those in more remote areas (p<0.001). CONCLUSIONS: A subsidy introduced at the top of the private sector supply chain can significantly increase usage of ACTs and reduce their retail price to the level of common monotherapies. Additional interventions may be needed to ensure access to ACTs in remote areas and for poorer individuals who appear to seek treatment at drug shops less frequently. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN39125414
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