Performance of a multigene genomic classifier and clinical parameters in predicting malignancy in a Southeast Asian cohort of patients with cytologically indeterminate thyroid nodules.

BACKGROUND: Most thyroid nodules are benign. It is important to determine the likelihood of malignancy in such nodules to avoid unnecessary surgery. The primary objective of this study was to characterize the genetic landscape and the performance of a multigene genomic classifier in fine-needle aspiration (FNA) biopsies of cytologically indeterminate thyroid nodules in a Southeast Asian cohort. The secondary objective was to assess the predictive contribution of clinical characteristics to thyroid malignancy. METHODS: This prospective, multicenter, blinded study included 132 patients with 134 nodules. Molecular testing (MT) with ThyroSeq v3 was performed on clinical or ex-vivo FNA samples. Centralized pathology review also was performed. RESULTS: Of 134 nodules, consisting of 61% Bethesda category III, 20% category IV, and 19% category V cytology, and 56% were histologically malignant. ThyroSeq yielded negative results in 37.3% of all FNA samples and in 42% of Bethesda category III-IV cytology nodules. Most positive samples had RAS-like (41.7%), followed by BRAF-like (22.6%), and high-risk (17.9%) alterations. Compared with North American patients, the authors observed a higher proportion of RAS-like mutations, specifically NRAS, in Bethesda categories III and IV and more BRAF-like mutations in Bethesda category III. The test had sensitivity, specificity, negative predictive value, and positive predictive value of 89.6%, 73.7%, 84.0%, and 82.1%, respectively. The risk of malignancy was predicted by positive MT and high-suspicion ultrasound characteristics according to American Thyroid Association criteria. CONCLUSIONS: Even in the current Southeast Asian cohort with nodules that had a high pretest cancer probability, MT could lead to potential avoidance of diagnostic surgery in 42% of patients with Bethesda category III-IV nodules. MT positivity was a stronger predictor of malignancy than clinical parameters.

Predicting nuclear maturation speed of oocytes from Japanese Black beef heifers through non-invasive observations during IVM: An attempt using machine learning algorithms.

Nuclear maturation is an essential process in which oocytes acquire the competence to develop further. However, the time required for nuclear maturation during IVM varies among oocytes. Therefore, predicting nuclear maturation speed (NMS) could help identify the optimal timing for IVF and maximize the developmental competence of each oocyte. This study aimed to establish machine learning-based prediction models for NMS using non-invasive indicators during the individual IVM of Japanese Black (JB) beef heifer oocytes. We collected ovaries from abattoirs and aspirated cumulus-oocyte complexes (COCs) from follicles with diameters ranging between 2 and 8 mm. The COCs were matured individually for 18 h, and photographs of each COC were taken at the beginning and every 3 h from 12 h to the end of maturation. After IVM culture, we denuded COCs and stained oocytes to confirm the progression of meiosis. Only oocytes that reached the metaphase II (MII) stage were considered to have a fast NMS. Morphological features, including COC area, cumulus expansion ratio, expansion rate per hour, and expansion pattern, were extracted from the recorded photos and applied to develop prediction models for NMS using machine learning algorithms. The MII rates of oocytes with fast- and slow-predicted NMS differed when the decision tree (DT) and random forest (RF) models were employed (P < 0.05). To evaluate the relationship between predicted NMS by DT and RF models and fertilization dynamics during individual IVF, sperm penetration and pronuclear formation were evaluated at 3, 6, 9, and 12 h after IVF start, following 24 h of IVM. The association between predicted NMS and embryo development was investigated by performing IVC for seven days using microwell culture dishes after 24 h of IVM and 6 h of IVF. Predicted NMS did not show a significant association with fertilization dynamics. However, oocytes with fast-predicted NMS by the RF model exhibited a tendency towards a higher cleavage rate 48 h after IVF start (P = 0.08); no other relationship was found between predicted NMS and embryo development. These findings demonstrate the feasibility of using non-invasive indicators during IVM to develop prediction models for NMS of JB beef heifer oocytes. Although the effect of predicted NMS on embryo development remains unclear, customized treatments based on NMS predictions have the potential to improve the efficiency of in vitro embryo production following individual IVM culture.

Penile gangrene from calciphylaxis is salvageable with intravenous sodium thiosulfate and early total parathyroidectomy.

Penile gangrene is a rare but fatal complication of calciphylaxis in end-stage renal disease (ESRD). To date, there are no guidelines on its management, and outcomes are generally poor with high mortality rate. We present a case of a diabetic patient with ESRD presenting with dry gangrene of the glans penis due to calciphylaxis and successfully treated with intravenous sodium thiosulfate (STS) and early total parathyroidectomy. We further analysed existing literatures on cases that utilized STS in the treatment of penile calciphylaxis.

New insight of ozone pollution impact from flare emissions of chemical plant start-up operations.

Flaring is a common and necessary operation for chemical industries, which is designed to manage dangerous process overpressure scenarios or to release and destroy off-spec products during chemical plant upsets or turnarounds. However, excessive flaring can emit large quantities of VOCs and NOx into the atmosphere, which will cause transient and localized ozone pollution events in the presence of sunlight. The objective of this study was to quantify the impact to regional air-quality due to flare emissions from chemical plant start-up operations through the coupling of dynamic process simulations via Aspen Plus and air-quality simulations via CAMx. Simulation results from case studies have indicated that the corresponding ozone increments can vary significantly from 0.2 ppb to 17.8 ppb under different temporal and spatial factors, including the start-up starting hour, starting day, and plant location. Additional ozone sensitivity simulations have also indicated that the corresponding ozone increments are higher when the plant is located in a VOC-limited area than that in a NOx-limited area. The results from this study have delivered a cost-effective air-quality control practice for plant start-ups with a minimum air-quality impact through selecting the optimal starting time within the allowable ranges. The practice has significant potential to benefit all stakeholders, including environmental agencies, chemical industries, and local communities.

Study on regional air quality impact from a chemical plant emergency shutdown.

Emergency shutdowns of chemical plants (ESCP) inevitably generate intensive and huge amounts of VOCs and NOx emissions through flaring that can cause highly localized and transient air pollution events with elevated ozone concentrations. However, quantitative studies of regional ozone impact due to ESCP, in terms of how ESCP would affect and to what extent ESCP could impact, are still lacking. This paper reports a systematic study on regional air quality impact from an olefin plant emergency shutdown due to the sudden failure of its cracked gas compressor (CGC). It demonstrates that emergency shutdown may cause significant ozone increment subject to different factors such as the starting time of emergency shutdown, flare destruction and removal efficiency (DRE) and plant location. In our studied case, the 8-hr ozone increment ranges from 0.4 to 3.3 ppb under different starting time, from 3.3 to 24.8 ppb under different DRE, and from 1.6 to 3.3 ppb under different locations. The results enable us to understand how and to what extent emergency operating activities of the chemical process will affect local air quality, which might be beneficial for decision makings on emergency air-quality response and control in the future.

Surgeon-Performed Ultrasound-Guided Fine-Needle Aspiration Cytology (SP-US-FNAC) Shortens Time for Diagnosis of Thyroid Nodules.

INTRODUCTION: Ultrasound-guided fine-needle aspiration cytology (US-FNAC) of thyroid nodules is an important diagnostic procedure. In most hospitals, patients are referred to radiologists for US-FNAC, but this often results in a long waiting time before results are available. Surgeon-performed US-FNAC (SP-US-FNAC) during the initial patient consultation attempts to reduce the waiting time but it is not known whether this is as accurate as radiologist-performed US-FNAC (RP-US-FNAC). The aim of this study is to compare the clinical efficiency between SP-US-FNAC and RP-US-FNAC. MATERIALS AND METHODS: A retrospective study was performed on patients from the Department of General Surgery, Tan Tock Seng Hospital (TTSH) who underwent an US-FNAC from August 2011 to May 2012. All cases of SP-US-FNAC were performed by a single surgeon. This study compared the rates of positive diagnoses achieved by SP-US-FNAC and RPUS- FNAC as well as the time interval to reach a cytological diagnosis by each group. RESULTS: A total of 40 cases of SP-US-FNAC and 72 cases of RP-US-FNAC were included in the study. SP-US-FNAC resulted in 28 (70%) positive diagnoses and 12 (30%) nondiagnoses while RP-US-FNAC resulted in 47 (65.3%) positive diagnoses and 25 (34.7%) non-diagnoses. These results were comparable (P=0.678). The median time taken to reach a cytological diagnosis was 1 working day for SP-US-FNAC and 29.5 working days for RP-US-FNAC resulting in a shorter interval to reaching a cytological diagnosis for SP-US-FNAC (P<0.001). CONCLUSION: In the workup of thyroid nodules, SP-US-FNAC is as accurate as RP-US-FNAC but significantly reduces the time taken to reach a cytological diagnosis. This leads to greater clinical efficiency in the management of patients with thyroid nodules, which in turn leads to other benefits such as decreased patient anxiety and increased patient satisfaction.

Acyl-coenzyme A:cholesterol acyltransferase 1 - significance of single-nucleotide polymorphism at residue 526 and the role of Pro347 near the fifth transmembrane domain.

Acyl-coenzyme A:cholesterol acyltransferases (ACATs), which are members of the membrane-bound O-acyltransferase family, catalyze the conversion of cholesterol to cholesteryl esters. Mammals have two isoenzymes: ACAT1 and ACAT2. Both enzymes are drug targets for treating human diseases. ACAT1 is present in various cell types. It contains nine transmembrane domains (TMDs), with the active site His460 located within TMD7, and the active site Asn421 located within the fourth large cytoplasmic loop. In human ACAT1, a single-nucleotide polymorphism exists for residue 526: the codon is either CAG for Gln, or CGG for Arg. Gln526/Arg526 is present within the C-terminal loop. Its biochemical significance is unknown. In addition, within the C-terminal half of ACAT1, numerous residues conserved with those of ACAT2 are present; the functions of these conserved residues are largely unknown. Here, we performed single-substitution mutagenesis experiments to investigate the roles of individual residues present in the C-terminal loop, including Gln526/Arg526, and the eight conserved Pro residues located near/in various TMDs. The results show that the enzyme activity of ACAT1 with Gln526 is less active than that of ACAT1 with Arg526 by 40%. In addition, several residues in the C-terminal loop are important for maintaining proper ACAT1 protein stability. Other results show that Pro347 plays an important role in modulating enzyme catalysis. Overall, our results imply that the CAG/CGG polymorphism can be utilized to perform ACAT1 activity/human disease susceptibility studies, and that Pro347 located near TMD5 plays an important role in modulating enzyme catalysis.

Microwave synthesized magnetic tubular carbon nanocomposite fabrics toward electrochemical energy storage.

Contrary to the helical carbon structure from pure cotton fabrics under microwave heating and radical oxidized ignition of nanoparticles from conventional heating, magnetic carbon tubular nanocomposite fabrics decorated with uniformly dispersed Co-Co(3)O(4) nanoparticles were successfully synthesized via a microwave heating process using cotton fabric and inorganic salt as precursors, which have shown better anti-corrosive performance and demonstrated great potential as novel electrochemical pseudocapacitor electrode.

Magnetic carbon nanostructures: microwave energy-assisted pyrolysis vs. conventional pyrolysis.

Magnetic carbon nanostructures from microwave assisted- and conventional-pyrolysis processes are compared. Unlike graphitized carbon shells from conventional heating, different carbon shell morphologies including nanotubes, nanoflakes and amorphous carbon were observed. Crystalline iron and cementite were observed in the magnetic core, different from a single cementite phase from the conventional process.

HIPEC + EPIC versus HIPEC-alone: differences in major complications following cytoreduction surgery for peritoneal malignancy.

INTRODUCTION: Peritoneal metastases (PM) can be treated with cytoreduction surgery (CRS) with intraoperative heated intraperitoneal chemotherapy (HIPEC) plus or minus early postoperative intraperitoneal chemotherapy (EPIC). HIPEC + EPIC may be associated with more complications than HIPEC alone. METHODS: A prospective database of consecutive patients undergoing CRS + HIPEC ± EPIC at the University of Calgary between February 2000 and May 2011 was reviewed. Patient, tumor, and perioperative variables included peritoneal cancer index (PCI), completeness of cytoreduction (CCR) score, HIPEC ± EPIC type, and grade III/IV complications. RESULTS: 198 patients had a CCR score of 0/1 and received: (1) HIPEC mitomycin C + EPIC 5-fluorouracil for 5 days (n = 85; February 2000-January 2008); or (2) HIPEC oxaliplatin with IV 5-fluorouracil + no EPIC (n = 113; February 2008-May 2011). Clinicodemographics were similar except PCI was higher in the HIPEC-alone group (mean PCI 22 vs. 17; P = 0.02). The rate of grade III/IV complications was higher in the HIPEC + EPIC group (44.7% vs. 31.0%; P = 0.05). On multivariate logistic regression only HIPEC + EPIC and PCI > 26 were associated with an increased rate of complications. CONCLUSION: In patients with PM, the use of EPIC, in combination with CRS and HIPEC, is associated with an increased rate of complications. Surgeons should consider using HIPEC only (without EPIC).

Utilization of thyroidectomy for benign disease in the United States: a 15-year population-based study.

BACKGROUND: Recent recommendations suggest that total thyroidectomy (TT) is the preferred treatment for benign thyroid disease. This approach remains controversial because of the increased risk of morbidity compared with a partial thyroidectomy (PT). The aim of this study was to determine the use of thyroidectomy for benign disease over a 15-year period. METHODS: One hundred nineteen thousand eight hundred eighty-five patients from the Nationwide Inpatient Sample database (1993-2007) underwent surgery for benign thyroid disease. Logistic regression was used to assess the relation between extent of thyroidectomy and the year of admission, hospital volume, and surgical outcomes. RESULTS: The use of TT increased from 17.6% (1993-1997) to 39.6% (2003-2007) compared with 82.4% and 60.4% for PT over the same periods (P < .0001). A greater proportion of TTs was performed in high-volume centers in which the rates of postoperative complications were lower than low-volume centers. CONCLUSIONS: The use of TT for benign thyroid disease has increased over the last 15 years in the United States. This pattern of practice is in keeping with the trends reported in recent literature.

Operative salvage for retroperitoneal nodal recurrence in colorectal cancer: a systematic review.

BACKGROUND: Retroperitoneal nodal recurrence after curative resection of colorectal cancer is an uncommon and challenging problem. The evidence for salvage surgery is limited and remains controversial, particularly when major vascular structures are involved. Some reports have demonstrated a survival benefit after metachronous resection of retroperitoneal metastasis with and without concomitant aortic resection. We conducted a systematic review of the literature to find evidence in favor of or against salvage surgery. METHODS: Electronic searches of the MEDLINE, Cochrane, and EMBASE database were performed. Additional papers were identified by a manual search of the references from the key articles. Only peer-reviewed articles published in the English language were evaluated. RESULTS: A total of nine suitable studies were identified: three case reports and six larger series, of which one was a case-control study. Including our case reports, the total number of patients who underwent surgical resection that are available for review was 110. Median overall survival was between 34 and 44 months and median disease-free survival between 17 and 21 months. Concomitant resection of major vessels with graft replacement was feasible with survival ranging from 19 months to 18 years. There was no reported mortality associated with surgical salvage of retroperitoneal recurrence and the overall morbidity was 17-33%. CONCLUSIONS: The current literature suggests that more aggressive surgical treatment of retroperitoneal nodal recurrence in CRC has acceptable morbidity and may be associated with an improved survival in well-selected patients.

iHeartLift: a closed loop system with bio-feedback that uses music tempo variability to improve heart rate variability.

"Musica delenit bestiam feram" translates into "Music soothes the savage beast". There is a hidden truth in this ancient quip passed down from generations. Besides soothing the heart, it also incites the heart to a healthier level of heart rate variability (HRV). In this paper, an approach to use and test music and biofeedback to increase the heart rate variability for people facing daily stress is discussed. By determining the music tempo variability (MTV) of a piece of music and current heart rate variability, iHeartLift is able to compare the 2 trends and locate a musical piece that is suited to increase the user's heart rate variability to a healthier level. With biofeedback, the 2 trends are continuously compared in real-time and the musical piece is changed in accordance with the current comparisons. A study was conducted and it was generally found that HRV can be uplifted by music regardless of language and meaning of musical lyrics but with limitations to musical genre.

Study of atmospheric mercury budget in East Asia using STEM-Hg modeling system.

East Asia is the largest source region of global anthropogenic mercury emissions, and contributes to atmospheric mercury concentration and deposition in other regions. Similarly, mercury from the global pool also plays a role in the chemical transport of mercury in East Asia. Annual simulations of atmospheric mercury in East Asia were performed using the STEM-Hg modeling system to study the mass budgets of mercury in the region. The model results showed strong seasonal variation in mercury concentration and deposition, with signals from large point sources. The annual mean concentrations for gaseous elemental mercury, reactive gaseous mercury and particulate mercury in central China and eastern coastal areas were 1.8 ng m(-3), 100 pg m(-3) and 150 pg m(-3), respectively. Boundary conditions had a strong influence on the simulated mercury concentration and deposition, contributing to 80% of the concentration and 70% of the deposition predicted by the model. The rest was caused by the regional emissions before they were transported out of the model domain. Using different oxidation rates reported for the Hg(0)-O(3) reaction (i.e., by Hall, 1995 vs. by Pal and Ariya, 2004) led to a 9% difference in the predicted mean concentration and a 40% difference in the predicted mean deposition. The estimated annual dry and wet deposition for East Asia in 2001 was in the range of 590-735 Mg and 482-696 Mg, respectively. The mercury mass outflow caused by the emissions in the domain was estimated to be 681-714 Mg yr(-1). This constituted 70% of the total mercury emission in the domain. The greatest outflow occurred in spring and early summer.

Information exchange protocol for mobile heart monitoring system.

The amount of information that can be gleamed from portable medical measuring apparatus is tremendous. Many portable medical apparatus manufacturers in the world are performing their own research and development to extract information. However, the data structure and protocol for the conveyance of the extracted information is left to the discretion of the manufacturers. This is because there is a lack of agreement on a standard data structure protocol format between such medical apparatus manufacturers to conform to a common communication and data transport protocol. Hence valuable extracted knowledge is left dispersed among these communities. This paper proposes an approach to a dynamic medical information exchange protocol to increase the interoperability of real-time medical measurements extracted by devices from medical industry manufacturers.

Evaluation of the apparent change in posterior corneal power in eyes with LASIK using Orbscan II with magnification compensation.

PURPOSE: To develop a mathematical model for the assessment of the apparent posterior corneal curvature changes after myopic keratorefractive surgery with Orbscan (Bausch & Lomb) and to assess its accuracy with clinical data. METHODS: Part 1: Postoperative and preoperative magnification ratio of the posterior corneal surface was calculated from a theoretical eye model. Changes of radius and power of the posterior corneal surface were estimated over a wide range of refractive corrections and preoperative anterior corneal power. Part 2: The measured radius of the posterior cornea by Orbscan II 3 months postoperatively was converted to a new value based on the mathematical model. Both the measured radius and corrected radius were compared with preoperative values using paired sample t test. RESULTS: Myopic correction is associated with apparent steepening of the posterior curvature. The higher the amount of correction, the more the apparent difference. A statistically significant difference was noted between preoperative and measured postoperative radius of the posterior cornea (0.35 +/- 0.16 mm, P<.01). However, no significant difference was seen between preoperative and corrected postoperative radius of the posterior cornea (0.008 +/- 0.11 mm, P=.44). CONCLUSIONS: The change of corneal magnification induced by refractive correction partly explains the apparent steepening of the posterior corneal curvature. The mathematical model effectively compensates for the error in Orbscan II in the assessment of posterior corneal curvature after LASIK.

Introducing a new ratio useful in the estimation of preoperative corneal power in patients with myopic LASIK based on postoperative corneal data.

AIM: The aim of this study was to establish a new constant ratio for the calculation of preoperative total corneal power using postoperative corneal data alone in patients after laser in situ keratomileusis (LASIK). METHODS: Preoperative anterior and posterior corneal radii from 192 pre-LASIK eyes were analyzed to derive a constant ratio in the first part of the study. In the second part of the study, with a set of post-LASIK patients (98 eyes), this ratio was used to estimate preoperative total corneal power. This estimated total corneal power was compared with the true value obtained from direct preoperative measurement. RESULTS: The ratio (R(roc)) between the preoperative anterior central 10-mm corneal curvature and the posterior peripheral 7- to 10-mm corneal curvature was 1.166 +/- 0.049. Estimated mean preoperative total corneal power was 43.42 +/- 2.21 D, whereas the true preoperative mean keratometric value (SimK) was 43.40 +/- 2.64 D. The mean difference was 0.02 +/- 2.65 D (P = 0.942). CONCLUSIONS: The pre-LASIK corneal power can be estimated using post-LASIK data together with R(roc). This will be useful in post-LASIK patients requiring cataract surgery but without the availability of pre-LASIK corneal data for the estimation of the preoperative keratometric power when the double-K technique was used to calculate the intraocular lens power.