Biogeosciences Perspectives on Integrated, Coordinated, Open, Networked (ICON) Science.

This article is composed of three independent commentaries about the state of Integrated, Coordinated, Open, Networked (ICON) principles in the American Geophysical Union Biogeosciences section, and discussion on the opportunities and challenges of adopting them. Each commentary focuses on a different topic: (a) Global collaboration, technology transfer, and application (Section 2), (b) Community engagement, community science, education, and stakeholder involvement (Section 3), and (c) Field, experimental, remote sensing, and real-time data research and application (Section 4). We discuss needs and strategies for implementing ICON and outline short- and long-term goals. The inclusion of global data and international community engagement are key to tackling grand challenges in biogeosciences. Although recent technological advances and growing open-access information across the world have enabled global collaborations to some extent, several barriers, ranging from technical to organizational to cultural, have remained in advancing interoperability and tangible scientific progress in biogeosciences. Overcoming these hurdles is necessary to address pressing large-scale research questions and applications in the biogeosciences, where ICON principles are essential. Here, we list several opportunities for ICON, including coordinated experimentation and field observations across global sites, that are ripe for implementation in biogeosciences as a means to scientific advancements and social progress.

Risk Factors that Predict Levothyroxine Medication after Thyroid Lobectomy.

CONTEXT AND OBJECTIVE: The risk of needing lifelong thyroid hormone supplementation is an important factor affecting treatment decisions for both patients and clinicians ahead thyroid lobectomy. The purposes of this study were to assess the predictive factors of levothyroxine medication after thyroid lobectomy. METHODS: We retrospectively reviewed 252 patients who had undergone lobectomy for benign thyroid nodules between April 2009 and April 2017. We conducted two independent analyses: patients who started taking levothyroxine after surgery were compared with those who did not, and patients who did not need levothyroxine at last follow-up were compared with those who required continued treatment. We investigated the correlations of patient clinicopathological characteristics and levothyroxine medication after lobectomy. RESULTS: Ninety-eight patients started levothyroxine after surgery. Of these, 34 patients successfully ceased medication and 64 patients continued treatment as of their last follow-up. In multivariate analysis, older age and preoperative TSH ≥2.0mIU/L were associated with levothyroxine initiation after surgery. In terms of continuity of levothyroxine, both older age and TSH ≥ 3.0mIU/L showed a significant correlation with continuous medication. We created a risk-scoring system to predict likelihood of starting and maintaining levothyroxine using the two significant factors in each comparison. A risk score of 3 or more indicated an increased risk of starting levothyroxine (specificity = 81.8%; sensitivity = 48.0%). A risk score of 3 or more indicated increased risk of continuous medication, (specificity = 94.2%; sensitivity = 35.9%). CONCLUSIONS: Greater age and higher preoperative TSH levels correlated with initiation and continuity of levothyroxine medication after lobectomy.

Clinical results of treatment of garden type 1 and 2 femoral neck fractures in patients over 70-year old.

INTRODUCTION: We retrospectively analyzed the clinical results of treatment of impacted or undisplaced femoral neck fractures (Garden types 1 and 2) by osteosynthesis in elderly patients >70-year old. MATERIALS AND METHODS: We retrospectively reviewed the radiological results of 52 patients who were followed up for at least 6 months from April 2002 to December 2008. The average age of the patients was 77.6 years (range 70-97 years), and 38 patients were females. The mean follow-up period was 11.7 months (range 6-19 months). Thirteen cases were Garden type 1 fractures, and 39 were Garden type 2 fractures. We assessed the relationships between the occurrence of complications and age, sex, Garden stage, bone mineral density (BMD), history of contralateral hip fracture, and any additional hip injury. RESULTS: Major complications occurred in 18 cases (34.6 %), including nonunion (8 cases), osteonecrosis (6 cases), stress fracture of the subtrochanter (2 cases), excessive pull-out of a screw (1 case), and deep infection (1 case). The development of complications was associated with Garden stage 2, BMD, and additional hip injury. However, other factors were not associated with complications. Reoperations were performed in 16 cases (30.1 %), and 2 of the patients died during follow-up. CONCLUSION: A relatively high rate of complications or reoperations developed after treatment of Garden 2 femoral neck fractures in senile patients >70 years of age with osteoporosis. Although internal fixation has been recommended in the literature for undisplaced femoral neck fractures, primary arthroplasty may be a better option for treatment of Garden type 2 fractures in elderly patients.

In vivo time-sequential histological study focused on melanocytes: suggestion of golden time for intervention to prevent post-laser pigmentary changes.

BACKGROUND: Post-inflammatory pigmentary changes after laser treatments are challenging adverse effect. OBJECTIVE: To suggest an ideal time period with regard to intervention to prevent post-laser pigmentary changes, an in vivo time-sequential histological study focused on melanocytes was performed. METHODS: The back skin of four volunteers was irradiated with Q-switched alexandrite laser (QSAL). In one subject (subject 4), topical corticosteroid was applied onto the irradiated skin from the time of irradiation to day 28. In all subjects, time-sequential skin biopsies were performed at baseline, an immediate time after irradiation, day 2, day 7, and day 28. Histological and immunohistochemical analyses were conducted. RESULTS: Q-switched alexandrite laser led to the successful removal of pigments and most melanocytes from the epidermis in all subjects. At day 28, there was increased epidermal pigmentation in the skin of the subjects 1-3. It was noted that numerous activated melanocytes appeared on day 7, continued to be observed until day 28. However, in the subject 4, the melanocyte activation and post-laser pigmentary changes were not observed. CONCLUSION: In regard to intervene melanocyte activation, at least 1 week after laser treatment is suggested as a 'golden' time period to prevent pigmentary changes.

Cytochalasin B inhibits the proliferation of human glioma U251 cells through cell cycle arrest and apoptosis.

Cytochalasin B (CB) is known to inhibit a number of cancer types, but its effects on gliomas are unknown. We examined the in vitro effects of CB on the proliferation of human glioma U251 cells, as well as determined its mechanism of action. Cell proliferation was determined using CCK-8. The effect of CB on U251 cell morphology was observed under a transmission electron microscope. Cell cycle distribution was assessed using propidium iodine and Giemsa staining, and cell apoptosis was determined by annexin V-fluorescein isothiocyanate/propidium iodide. Cell cycle-related proteins were determined by Western blot. CB effectively inhibited U251 cell proliferation in a dose- and time-dependent manner. The 24, 48, 72, and 96 h IC50 values were 6.41 x 10(-2), 9.76 x 10(-4), 2.57 x 10(-5), and 2.08 x 10(-5) M, respectively. CB increased the proportion of cells in the G2/M phase in a dose-dependent manner, thus increasing the mitotic index and decreasing cdc2 and cyclin B1 protein levels. CB induced morphological changes in the cytoskeleton. Additionally, 10(-5) M CB induced apoptosis in 23.4 ± 0.5% of U251 cells (P < 0.05 vs control group). Caspase-3, -8, and -9 activities were increased after CB treatment. CB inhibited U251 glioma cell proliferation by damaging the microfilament structure. CB also induced glioma cell apoptosis, suggesting that it may be an effective therapeutic agent against gliomas.

Impact of MTHFR polymorphisms on methylation of MGMT in glioma patients from Northeast China with different folate levels.

Hypomethylation of the O6-methylguanine-DNA-methyltransferase (MGMT) promoter in glioma cells has been associated with temozolomide resistance. S-adenosylmethionine (SAM), which is produced during folate metabolism, is the main source of methyl groups during DNA methylation. As a key enzyme during folate metabolism, polymorphisms of 5,10-methylenetetrahydrofolate reductase (MTHFR) may regulate folate end-products. We investigated the effect of typical polymorphisms of MTHFR (C677T and A1298C) on MGMT methylation based on different serum folate levels in patients with glioma from Northeast China. A total of 275 patients with glioma and 329 without malignant tumors were tested. Serum folate concentration was assayed by using the electrochemiluminescence immunoassay. MTHFR polymorphisms were detected by Taqman-Fluorescence quantitative polymerase chain reaction (PCR). Methylation-specific PCR was used to assess MGMT methylation. The constituent ratio of glioma patients below the serum folate biological reference value was significantly higher than that of the control population (P < 0.001). In patients with oligodendroglioma and glioblastoma, heterozygotes for the A1298C mutation were found in higher frequency than homozygotes or wild types (oligodendroglioma, P < 0.001; glioblastoma, P < 0.01). When grouped by the median or biological reference value of serum folate, only homozygotes for C677T with low levels of folate were significantly associated with decreased methylation of MGMT (median, P < 0.001; biological reference value, P = 0.036). These data suggest that, in combination with a negative folate balance in glioma patients, T/T genotypes in MTHFR C677T may be associated with MGMT demethylation.

High-performance top-gated monolayer SnS2 field-effect transistors and their integrated logic circuits.

Two-dimensional (2D) layered semiconductors are very promising for post-silicon ultrathin channels and flexible electronics due to the remarkable dimensional and mechanical properties. Besides molybdenum disulfide (MoS2), the first recognized 2D semiconductor, it is also important to explore the wide spectrum of layered metal chalcogenides (LMCs) and to identify possible compounds with high performance. Here we report the fabrication of high-performance top-gated field-effect transistors (FETs) and related logic gates from monolayer tin disulfide (SnS2), a non-transition metal dichalcogenide. The measured carrier mobility of our monolayer devices reaches 50 cm(2) V(-1) s(-1), much higher than that of the back-gated counterparts (~1 cm(2) V(-1) s(-1)). Based on a direct-coupled FET logic technique, advanced Boolean logic gates and operations are also implemented, with a voltage gain of 3.5 and output swing of >90% for the NOT and NOR gates, respectively. The superior electrical and integration properties make monolayer SnS2 a strong candidate for next-generation atomic electronics.

Factors influencing medical student attrition and their implications in a large multi-center randomized education trial.

Participant attrition may be a significant threat to the generalizability of the results of educational research studies if participants who do not persist in a study differ from those who do in ways that can affect the experimental outcomes. A multi-center trial of the efficacy of different computer-based instructional strategies gave us the opportunity to observe institutional and student factors linked to attrition from a study and the ways in which they altered the participation profile. The data is from a randomized controlled trial conducted at seven US medical schools investigating the educational impact of different instructional designs for computer-based learning modules for surgical clerks. All students undertaking their surgical clerkships at the participating schools were invited participate and those that consented were asked to complete five study measures during their surgery clerkship. Variations in study attrition rates were explored by institution and by participants' self-regulation, self-efficacy, perception of task value, and mastery goal orientation measured on entry to the study. Of the 1,363 invited participants 995 (73 %) consented to participate and provided baseline data. There was a significant drop in the rate of participation at each of the five study milestones with 902 (94 %) completing at least one of two module post-test, 799 (61 %) both module post-tests, 539 (36 %) the mid-rotation evaluation and 252 (25 %) the final evaluation. Attrition varied between institutions on survival analysis (p < 0.001). Small but statistically significant differences in self-regulation (p = 0.01), self-efficacy (p = 0.02) and task value (p = 0.04) were observed but not in mastery or performance goal orientation measures (p = NS). Study attrition was correlated with lower achievement on the National Board of Medical Examiners subject exam. The results of education trials should be interpreted with the understanding that students who persist may be somewhat more self-regulated, self-efficacious and higher achievers than their peers who drop out and as such do not represent the class as a whole.

Just enough, but not too much interactivity leads to better clinical skills performance after a computer assisted learning module.

BACKGROUND: Well-designed computer-assisted instruction (CAI) can potentially transform medical education. Yet little is known about whether specific design features such as direct manipulation of the content yield meaningful gains in clinical learning. We designed three versions of a multimedia module on the abdominal exam incorporating different types of interactivity. METHODS: As part of their physical diagnosis course, 162 second-year medical students were randomly assigned (1:1:1) to Watch, Click or Drag versions of the abdominal exam module. First, students' prior knowledge, spatial ability, and prior experience with abdominal exams were assessed. After using the module, students took a posttest; demonstrated the abdominal exam on a standardized patient; and wrote structured notes of their findings. RESULTS: Data from 143 students were analyzed. Baseline measures showed no differences among groups regarding prior knowledge, experience, or spatial ability. Overall there was no difference in knowledge across groups. However, physical exam scores were significantly higher for students in the Click group. CONCLUSIONS: A mid-range level of behavioral interactivity was associated with small to moderate improvements in performance of clinical skills. These improvements were likely mediated by enhanced engagement with the material, within the bounds of learners' cognitive capacity. These findings have implications for the design of CAI materials to teach procedural skills.

Origin of the relatively low transport mobility of graphene grown through chemical vapor deposition.

The reasons for the relatively low transport mobility of graphene grown through chemical vapor deposition (CVD-G), which include point defect, surface contamination, and line defect, were analyzed in the current study. A series of control experiments demonstrated that the determinant factor for the low transport mobility of CVD-G did not arise from point defects or surface contaminations, but stemmed from line defects induced by grain boundaries. Electron microscopies characterized the presence of grain boundaries and indicated the polycrystalline nature of the CVD-G. Field-effect transistors based on CVD-G without the grain boundary obtained a transport mobility comparative to that of Kish graphene, which directly indicated the detrimental effect of grain boundaries. The effect of grain boundary on transport mobility was qualitatively explained using a potential barrier model. Furthermore, the conduction mechanism of CVD-G was also investigated using the temperature dependence measurements. This study can help understand the intrinsic transport features of CVD-G.

Field electron emission of ZnO nanowire pyramidal bundle arrays.

A facile hydrothermal method was adopted to in situ grow ZnO nanowire pyramidal bundle arrays on zinc substrates at low growth temperature without the assistance of catalysts and templates. The bundle arrays were shown to form by sticking of nanowires at their tips. Field electron emission characterization of nanowires bundle arrays revealed a very low turn-on electric field of about 2.3 V/microm and a threshold electric field (corresponding to the field electron emission current density of 10 mA/cm2) of 6.8 V/microm, which are comparable to those observed in carbon nanotube arrays. The bundle arrays also show pronounced long-term field electron emission stability at a high current density. In addition, the formation mechanism of the pyramidal bundled arrays and the origin of the peculiar field electron emission properties were discussed.

High-quality Graphenes via a facile quenching method for field-effect transistors.

Single- and few-layer graphene sheets with sizes up to 0.1 mm were fabricated by simply quenching hot graphite in an ammonium hydrogen carbonate aqueous solution. The identity and thickness of graphene sheets were characterized with transmission electron microscopy, atomic force microscopy, and Raman spectroscopy. In addition to its simplicity and scalability, the present synthesis can produce graphene sheets with excellent qualities in terms of sizes, purity, and crystal quality. The as-produced graphene sheets can be easily transferred to solid substrates for further processing. Field-effect transistors based on individual graphenes were fabricated and shown to have high ambipolar carrier mobilities.

Phase II study and biomarker analysis of cetuximab combined with modified FOLFOX6 in advanced gastric cancer.

This prospective study was conducted with the Korean Cancer Study Group to evaluate the efficacy and safety of cetuximab combined with modified FOLFOX6 (mFOLFOX6) as first-line treatment in recurrent or metastatic gastric cancer and to identify potential predictive biomarkers. Patients received cetuximab 400 mg m(-2) at week 1 and 250 mg m(-2) weekly thereafter until disease progression. Oxaliplatin (100 mg m(-2)) and leucovorin (100 mg m(-2)) were administered as a 2-h infusion followed by a 46-h continuous infusion of 5-fluorouracil (2400 mg m(-2)) every 2 weeks for a maximum of 12 cycles. Biomarkers potentially associated with efficacy were analysed. Among 38 evaluable patients, confirmed response rate (RR) was 50.0% (95% CI 34.1-65.9). Median time-to-progression (TTP) was 5.5 months (95% CI 4.5-6.5) and overall survival (OS) 9.9 months. Eleven patients having tumour EGFR expression by immunohistochemistry with low serum EGF and TGF-alpha levels showed a 100% RR compared to 37.0% in the remaining 27 patients (P<0.001). Moreover, ligand level increased when disease progressed in seven out of eight patients with EGFR expression and low baseline ligand level. No patient exhibited EGFR amplification or K-ras mutations. Gastric cancer patients with EGFR expression and low ligand levels had better outcomes with cetuximab/mFOLFOX6 treatment.

Multicenter phase II study of docetaxel plus oxaliplatin combination chemotherapy in patients with advanced gastric cancer: Daegu Gyeongbuk Oncology Group.

The present study was conducted to evaluate the efficacy and safety of a combination regimen of docetaxel plus oxaliplatin in patients with advanced gastric cancer. Patients with previously untreated metastatic or recurrent, measurable gastric cancer received intravenous docetaxel 65 mg m(-2) plus oxaliplatin 120 mg m(-2) on day 1 based on a 3-week cycle. Forty-two patients were enrolled in the current study, among whom 39 were assessable for efficacy and all assessable for toxicity. One complete response and 18 partial responses were confirmed, giving an overall response rate of 45.2% (95% confidence interval (CI); 31.7-59.7%). At a median follow-up of 7.7 months, the median time to progression and median overall survival was 5.7 (95% CI; 4.3-7.2) months and 9.9 (95% CI; 7.8-12.0) months, respectively. Grade 3/4 neutropenia occurred in 11 patients (26.1%) and febrile neutropenia was observed in four patients (9.5%). The common non-haematologic toxicity was fatigue (grade 1/2, 61.9%) and nausea (grade 1/2, 47.7%). The combination of docetaxel and oxaliplatin was found to be well tolerated and effective in patients with advanced gastric cancer.

Vertically aligned p-type single-crystalline GaN nanorod arrays on n-type Si for heterojunction photovoltaic cells.

Vertically aligned Mg-doped GaN nanorods have been epitaxially grown on n-type Si substrate to form a heterostructure for fabricating p-n heterojunction photovoltaic cells. The p-type GaN nanorod/n-Si heterojunction cell shows a well-defined rectifying behavior with a rectification ratio larger than 10(4) in dark. The cell has a high short-circuit photocurrent density of 7.6 mAlcm2 and energy conversion efficiency of 2.73% under AM 1.5G illumination at 100 mW/cm2. Moreover, the nanorod array may be used as an antireflection coating for solar cell applications to effectively reduce light loss due to reflection. This study provides an experimental demonstration for integrating one-dimensional nanostructure arrays with the substrate to directly fabricate heterojunction photovoltaic cells.

High-aspect-ratio aluminum borate nanowire bundles supported by sucrose.

High-aspect-ratio and single-crystal aluminum borate (Al(18)B(4)O(33)) nanowire bundles with an ordered orientation were synthesized by using an innovative sucrose-assisted growth process. The process involves the dehydration and polycondensation of aluminum borate-sucrose solution to form a highly viscous precursor. The sucrose plays a crucial role in the growth of the nanowire bundles by supporting as a polymeric substrate and a type of adhesive template. Electron microscopy was used to characterize the high-aspect-ratio nanowire bundles. A possible growth mechanism for the nanowire bundles is proposed.

Improved therapeutic outcomes of DLBCL after introduction of rituximab in Korean patients.

The addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) has been shown to improve the outcome in all age groups with newly diagnosed diffuse large B-cell lymphoma (DLBCL). We conducted a retrospective analysis to evaluate the impact of this combination therapy on DLBCL outcomes in Korea. From October 2001 to June 2004, newly diagnosed DLBCL patients in nine Korean institutes were included. All of these 81 patients were treated with three or more cycles of rituximab plus CHOP (R-CHOP) combination chemotherapy (R group), and followed for a minimum of 12 months. For comparison, a historical cohort of patients was used and analyzed for "Clinicopathologic characteristics of Korean non-Hodgkin's lymphomas (NHLs) based on Revised American Lymphoma (REAL) classification" in 1999. Among the 1,098 NHL patients, the data of 214 DLBCL patients, who were treated with CHOP chemotherapy in first-line, were analyzed (C group). We compared outcomes between the C group and the R group. A total of 295 patients were evaluated (C group, 214; R group, 81). The complete response (CR) rate was higher in R group (73 vs 91%, p=0.001). The 2-year event-free survival (EFS) rate was significantly higher in R group (78 vs 85%, p=0.0194). This survival benefit was maintained in high-risk patients according to the international prognostic index (IPI) (p=0.0039), regardless of age. However, there was no significant difference in low-risk patients. The addition of rituximab to CHOP combination chemotherapy for DLBCLs showed improved outcomes, particularly in high-risk group according to the IPI. Long-term follow-up results will be needed to confirm these results.