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1.
Sci Total Environ ; 918: 170725, 2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38325471

ABSTRACT

The Net Zero Emissions (NZE) concept has created momentum for climate commitment made by national governments, cities, industries and individual companies. However, evidence of tangible decarbonisation is limited. Here we identify precarious differences between the scientific origin of NZE and its social representation in the wider public and explore the consequences of the resulting science-action gap for achieving global climate goals. A particular focus is given to 'offsetting', which is closely connected to the practical delivery of NZE but typically ignores that different types or carbon credits have different environmental efficacy. Revisiting the science related to the global carbon cycle demonstrates that a heavy reliance on any carbon offsetting that is not a permanent removal presents a real risk. Moreover, competition over scarce 'removal credits' distracts from the real tasks at hand, namely to rapidly decrease fossil fuel emissions, actively remove carbon through restoration, and protect existing terrestrial carbon sinks. Establishing separate targets for these distinct actions is an essential step towards disentangling current confusion. Whilst a 'race to net zero' may trigger innovation in the decarbonisation space, the restoration and protection of carbon sinks demands a collective approach where actors should focus on how to make real and verifiable contributions rather than claiming individual net zero scores.

2.
Tech Coloproctol ; 28(1): 25, 2024 01 17.
Article in English | MEDLINE | ID: mdl-38231341

ABSTRACT

BACKGROUND: Total mesorectal excision using conventional straight fixed devices may be technically difficult because of the narrow and concave pelvis. Several laparoscopic articulating tools have been introduced as an alternative to robotic systems. The aim of this study was to compare perioperative outcomes between laparoscopic low anterior resection using ArtiSential® and robot-assisted surgery for rectal cancer. METHODS: This retrospective study included 682 patients who underwent laparoscopic or robotic low anterior resection  for rectal cancer from September 2018 to December 2021. Among them, 82 underwent laparoscopic surgery using ArtiSential® (group A) and 201 underwent robotic surgery (group B). A total of 73 [group A; 66.37 ± 11.62; group B 65.79 ± 11.34] patients were selected for each group using a propensity score matching analysis. RESULTS: There was no significant difference in the baseline characteristics between group A and B. Mean operative time was longer in group B than A (163.5 ± 61.9 vs 250.1 ± 77.6 min, p < 0.001). Mean length of hospital stay was not significantly different between the two groups (6.2 ± 4.7 vs 6.7 ± 6.1 days, p = 0.617). Postoperative complications, reoperation, and readmission within 30 days after surgery were similar between the two groups. Pathological findings revealed that the circumferential resection margins were above 10 mm in both groups (11.00 ± 7.47 vs 10.17 ± 6.25 mm, p = 0.960). At least 12 lymph nodes were sufficiently harvested, with no significant difference in the number harvested between the groups (20.5 ± 9.9 vs 19.7 ± 7.3, p = 0.753). CONCLUSIONS: Laparoscopic low anterior resection using ArtiSential® can achieve acceptable clinical and oncologic outcomes. ArtiSential®, a multi-joint and articulating device, may serve a feasible alternative approach to robotic surgery in rectal cancer.


Subject(s)
Laparoscopy , Rectal Neoplasms , Robotic Surgical Procedures , Humans , Propensity Score , Retrospective Studies , Rectal Neoplasms/surgery
3.
Atmos Environ (1994) ; 244: 117834, 2021 Jan 01.
Article in English | MEDLINE | ID: mdl-32895604

ABSTRACT

Global aviation operations contribute to anthropogenic climate change via a complex set of processes that lead to a net surface warming. Of importance are aviation emissions of carbon dioxide (CO2), nitrogen oxides (NOx), water vapor, soot and sulfate aerosols, and increased cloudiness due to contrail formation. Aviation grew strongly over the past decades (1960-2018) in terms of activity, with revenue passenger kilometers increasing from 109 to 8269 billion km yr-1, and in terms of climate change impacts, with CO2 emissions increasing by a factor of 6.8 to 1034 Tg CO2 yr-1. Over the period 2013-2018, the growth rates in both terms show a marked increase. Here, we present a new comprehensive and quantitative approach for evaluating aviation climate forcing terms. Both radiative forcing (RF) and effective radiative forcing (ERF) terms and their sums are calculated for the years 2000-2018. Contrail cirrus, consisting of linear contrails and the cirrus cloudiness arising from them, yields the largest positive net (warming) ERF term followed by CO2 and NOx emissions. The formation and emission of sulfate aerosol yields a negative (cooling) term. The mean contrail cirrus ERF/RF ratio of 0.42 indicates that contrail cirrus is less effective in surface warming than other terms. For 2018 the net aviation ERF is +100.9 milliwatts (mW) m-2 (5-95% likelihood range of (55, 145)) with major contributions from contrail cirrus (57.4 mW m-2), CO2 (34.3 mW m-2), and NOx (17.5 mW m-2). Non-CO2 terms sum to yield a net positive (warming) ERF that accounts for more than half (66%) of the aviation net ERF in 2018. Using normalization to aviation fuel use, the contribution of global aviation in 2011 was calculated to be 3.5 (4.0, 3.4) % of the net anthropogenic ERF of 2290 (1130, 3330) mW m-2. Uncertainty distributions (5%, 95%) show that non-CO2 forcing terms contribute about 8 times more than CO2 to the uncertainty in the aviation net ERF in 2018. The best estimates of the ERFs from aviation aerosol-cloud interactions for soot and sulfate remain undetermined. CO2-warming-equivalent emissions based on global warming potentials (GWP* method) indicate that aviation emissions are currently warming the climate at approximately three times the rate of that associated with aviation CO2 emissions alone. CO2 and NOx aviation emissions and cloud effects remain a continued focus of anthropogenic climate change research and policy discussions.

4.
Br J Surg ; 107(1): 64-72, 2020 01.
Article in English | MEDLINE | ID: mdl-31609482

ABSTRACT

BACKGROUND: The aim was to characterize end-of-life care in patients who have had a leg amputated for peripheral artery disease (PAD) or diabetes. METHODS: This was a population-based retrospective cohort study of patients with PAD or diabetes who died in Ontario, Canada, between 2011 and 2017. Those who had a leg amputation within 3 years of death were compared with a control cohort of deceased patients with PAD or diabetes, but without leg amputation. The patients were identified from linked health records within the single-payer healthcare system. Place and cause of death, as well as health services and costs within 90 days of death, were compared between the amputee and control cohorts. Among amputees, multivariable regression models were used to characterize the association between receipt of home palliative care and in-hospital death, as well as time spent in hospital at the end of life. RESULTS: Compared with 213 300 controls, 3113 amputees were less likely to die at home (15·5 versus 24·9 per cent; P < 0·001) and spent a greater number of their last 90 days of life in hospital (median 19 versus 8 days; P < 0·001). Amputees also had higher end-of-life healthcare costs across all sectors. However, receipt of palliative care was less frequent among amputees than controls (inpatient: 13·4 versus 16·8 per cent, P < 0·001; home: 14·5 versus 23·8 per cent, P < 0·001). Among amputees, receipt of home palliative care was associated with a lower likelihood of in-hospital death (odds ratio 0·49, 95 per cent c.i. 0·40 to 0·60) and fewer days in hospital (rate ratio 0·84, 0·76 to 0·93). CONCLUSION: Palliative care is underused after amputation in patients with PAD or diabetes, and could contribute to reducing in-hospital death and time spent in hospital at the end of life.


ANTECEDENTES: Caracterizar la atención al final de la vida en pacientes con amputación de la extremidad inferior por enfermedad arterial periférica (peripheral arterial disease, PAD) o diabetes. MÉTODOS: Se trata de un estudio de cohortes retrospectivo de base poblacional en sujetos fallecidos con PAD o diabetes en Ontario, Canadá (2011-2017). A partir de los registros sanitarios incluidos en un sistema de salud de una sola entidad pagadora, se identificaron los individuos con amputación de la extremidad inferior en los 3 años previos al fallecimiento y una cohorte control de fallecidos con PAD o diabetes sin amputación. Entre las cohortes de amputados y controles se comparó el lugar del fallecimiento y la causa, así como el uso de servicios sanitarios y costes en los últimos 90 días de vida. En el grupo de los amputados, se utilizaron modelos de regresión para caracterizar la asociación entre recibir cuidados paliativos domiciliarios y el fallecimiento en el hospital, así como los días de estancia hospitalaria al final de la vida. RESULTADOS: En comparación con los controles (n = 213.300), los sujetos con amputación (n = 3.113) era menos probable que fallecieran en el domicilio (16% versus 25%, P < 0,001) y pasaron un mayor número de sus últimos 90 días de vida en el hospital (mediana 19 versus 8 días, P < 0,001). Los costes de atención sanitaria al final de la vida en todos los sectores también fueron mayores para los amputados. Sin embargo, recibir cuidados paliativos fue menos frecuente en los amputados que en los controles (en el hospital 13% versus 17%, P < 0,001; domiciliarios 14% versus 24%, P < 0,001). En el grupo de los amputados, recibir cuidados paliativos domiciliarios se asociaba con una menor probabilidad de fallecimiento en el hospital (razón de oportunidades, odds ratio 0,49, i.c. del 95% 0,40-0,60) y menos días de hospitalización (tasa de riesgo 0,84, i.c. del 95% 0,76-0,93). CONCLUSIÓN: Los cuidados paliativos están infrautilizados en pacientes con PAD o diabetes y pueden contribuir a disminuir los fallecimientos en el hospital y los días de hospitalización al final de la vida.


Subject(s)
Amputation, Surgical/mortality , Diabetes Complications/mortality , Peripheral Arterial Disease/mortality , Terminal Care/methods , Aged , Aged, 80 and over , Amputation, Surgical/economics , Cause of Death , Diabetes Complications/economics , Diabetes Complications/surgery , Female , Health Care Costs , Home Care Services/economics , Home Care Services/statistics & numerical data , Hospitalization/statistics & numerical data , Humans , Male , Ontario/epidemiology , Palliative Care/economics , Palliative Care/methods , Palliative Care/statistics & numerical data , Peripheral Arterial Disease/economics , Peripheral Arterial Disease/therapy , Terminal Care/economics , Terminal Care/statistics & numerical data
5.
Colloids Surf B Biointerfaces ; 184: 110500, 2019 Dec 01.
Article in English | MEDLINE | ID: mdl-31541889

ABSTRACT

In this work, the extraordinary properties of CuO addition on the morphology and supercapacitive performance of Mn2O3 electrodes were demonstrated. Concisely, CuO/Mn2O3 thin films were prepared by an easy and inexpensive successive ionic layer adsorption and reaction (SILAR) method. The prepared thin films were characterized by various sophisticated physiochemical systems. The results demonstrated formation of Mn2O3 thin films with noteworthy morphological alteration upon introduction of CuO. Furthermore, a significant effect of CuO introduction was observed on the electrocatalytic properties of the nanostructured Mn2O3 electrodes. At 3% CuO doping, the Mn2O3 electrodes displayed the maximum specific capacitance owing to formation of nanoplate-like structures. The enhanced specific capacitance attained for 3% CuO doping in the Mn2O3 electrode was 500 F/g at 5 mV/s in a 3 M KOH electrolyte. All results confirmed the plausible potential of the CuO/Mn2O3 electrode for supercapacitor applications.


Subject(s)
Copper/chemistry , Electric Capacitance , Manganese Compounds/chemistry , Nanostructures/chemistry , Oxides/chemistry , Electrodes , Nanotubes/chemistry , Particle Size , Surface Properties
6.
J Dent Res ; 98(11): 1239-1244, 2019 10.
Article in English | MEDLINE | ID: mdl-31425664

ABSTRACT

Dentin hypersensitivity commonly occurs due to opened dentinal tubules for many reasons. In our previous study, copine 7 (CPNE7) could induce dentin formation for an indirect pulp-capping model in vivo. This study aims to investigate the formation of tertiary dentin when CPNE7 is applied to intentionally exposed dentin with nothing over it in vivo, whether it affects microleakage of the teeth, and the penetration ability of CPNE7 molecules through dentinal tubules in vitro. Cervical dentin areas of 6 maxillary incisors of 5 beagles were exposed to a class V-like lesion, and 1 side of 3 maxillary incisors was adapted with recombinant CPNE7 protein for 5 min as the experimental group. The other side was the control group, and there was no treatment of ethylenediaminetetraacetic acid (EDTA) and CPNE7 after preparation. The defects were exposed without any restorations, and all beagles were sacrificed after 4 wk. The fluid penetration of exposed dentin areas was investigated by a microleakage-testing device and confocal laser scanning microscope. Tertiary dentin formation was confirmed with histological scanning electronic microscopic analysis. Tertiary dentin formation reduces dentinal fluid flow due to occluded tubules or discontinuity with primary or secondary dentin. The in vivo hypersensitivity model with the anterior teeth of beagle dogs showed newly formed tertiary dentin at the dentin-pulp boundary in recombinant CPNE7-treated teeth when compared with the untreated control group in histologic analysis. Scanning electronic microscopic analysis revealed occluded sites with mineral deposition of intratubular dentin. In the permeability test, the mean microleakage value of the CPNE7-treated group was significantly lower than that of the control group (P < 0.05). The tubular penetration of rhodamine B-combined CPNE7 was confirmed under confocal laser scanning microscope. CPNE7 induces formation of tertiary dentin through shallowly exposed dentinal tubules, which decreases dentin permeability.


Subject(s)
Dentin Sensitivity/therapy , Dentin, Secondary , Membrane Proteins/therapeutic use , Animals , Dental Pulp Capping , Dogs , Microscopy, Electron, Scanning
7.
Cell Tissue Res ; 374(3): 531-540, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30091046

ABSTRACT

Enamel makes up the outermost layer of the crown and its hardness protects other dental tissues from various stimuli. Enamel cannot be regenerated once damaged because ameloblasts are lost during the tooth eruption. Since the ameloblast differentiation mechanism is still unknown, further research is essential for developing treatments for defective or damaged enamel. Previously, we have reported that osteoblast differentiation and bone formation were regulated through the runt-related transcription factor 2 (Runx2)-nuclear factor 1-C (Nfic)-osterix (Osx) pathway where Nfic directly controls Osx expression. This pathway regulates odontoblast differentiation and dentin formation as well. The aim of this study was to investigate if the same pathway is applicable for ameloblast differentiation. Structural enamel defects with disorganized ameloblasts and decreased proliferation activity of the cervical loop were observed in Nfic-/- mice incisors. Expression of the ameloblast differentiation markers was also downregulated significantly in Nfic-/- mice. Real-time PCR analyses suggested that Runx2, Nfic, and Osx regulate the expression of ameloblast differentiation markers, where Runx2 is upstream of Nfic, and Nfic controls Osx expression. Therefore, we suggest the Runx2-Nfic-Osx pathway as one of the key factors that regulate ameloblast differentiation.


Subject(s)
Ameloblasts/cytology , Ameloblasts/metabolism , Cell Differentiation , Dental Enamel/metabolism , NFI Transcription Factors/metabolism , Signal Transduction , Sp7 Transcription Factor/metabolism , Animals , Biomarkers/metabolism , Cell Line , Cell Lineage , Cell Proliferation , Core Binding Factor Alpha 1 Subunit/metabolism , Dental Enamel/ultrastructure , Mice , NFI Transcription Factors/deficiency , Tooth/metabolism , Tooth/ultrastructure , X-Ray Microtomography
8.
Physiol Res ; 67(3): 487-494, 2018 07 17.
Article in English | MEDLINE | ID: mdl-29527922

ABSTRACT

Spinal deformities such as scoliosis and kyphosis are incurable, and can lead to decreased physical function, pain, and reduced quality of life. Despite much effort, no clear therapies for the treatment of these conditions have been found. Therefore, the development of an animal model for spinal deformity would be extremely valuable to our understanding of vertebral diseases. In this study, we demonstrate that mice deficient in the mitochondrial enzyme isocitrate dehydrogenase 2 (IDH2) develop spinal deformities with aging. We use morphological analysis as well as radiographic and micro-CT imaging of IDH2-deficient mice to characterize these deformities. Histological analysis showed increased abnormalities in IDH2-deficient mice compared to wild type mice. Taken together, the results suggest that IDH2 plays a critical role in maintaining the spinal structure by affecting the homeostatic balance between osteoclasts and osteoblasts. This indicates that IDH2 might be a potent target for the development of therapies for spinal deformities. Our findings also provide a novel animal model for vertebral disease research.


Subject(s)
Disease Models, Animal , Isocitrate Dehydrogenase/genetics , Spinal Diseases/etiology , Aging/pathology , Animals , Mice, Knockout , Spinal Diseases/diagnostic imaging , Spinal Diseases/pathology , Spine/pathology , X-Ray Microtomography
9.
Colloids Surf B Biointerfaces ; 164: 255-261, 2018 Apr 01.
Article in English | MEDLINE | ID: mdl-29413604

ABSTRACT

In this paper, we chemically synthesized interconnected nanoflake-like CdS thin films for photoelectrochemical solar cell applications and subsequently irradiated them with electron beam irradiation at various doses of irradiation. The as-synthesized and irradiated samples were characterized by means of X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), high-resolution transmission electron microscopy (HR-TEM), and electrochemical measurements. XRD and XPS results confirmed the formation of CdS with a hexagonal crystal structure. FE-SEM and HR-TEM studies confirmed the photoelectrochemical performance, which was dependent on the surface morphology. The calculated values for efficiency demonstrated an outstanding photoelectrochemical performance with a fill factor of 0.38 and efficiency of 3.06% at 30 kGy. The high photoelectrochemical performance may be due to the interconnected nanoflake-like nanostructure and higher active surface area of the CdS samples. These results show that the electron beam irradiation is capable as an electrode for photoelectrochemical solar cells.


Subject(s)
Cadmium Compounds/chemistry , Electrochemical Techniques/methods , Electrons , Nanostructures/chemistry , Photochemistry/methods , Sulfides/chemistry , Electrodes , Nanostructures/ultrastructure , Optical Phenomena , Photoelectron Spectroscopy , Solar Energy , X-Ray Diffraction
10.
Ann R Coll Surg Engl ; 99(7): e196-e199, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28853592

ABSTRACT

Diaphragmatic eventration is an uncommon condition, usually discovered incidentally in asymptomatic patients. Even in symptomatic patients, the diagnosis can be challenging and should be considered among the differential diagnoses of diaphragmatic hernia. The correct diagnosis can often only be made in surgery. We describe the case of a 31-year-old patient with diaphragmatic eventration that was misdiagnosed as a recurrent congenital diaphragmatic hernia and review the corresponding literature.


Subject(s)
Diaphragmatic Eventration/diagnosis , Hernia, Diaphragmatic/diagnosis , Adult , Diagnosis, Differential , Diagnostic Errors , Diaphragmatic Eventration/diagnostic imaging , Diaphragmatic Eventration/surgery , Hernia, Diaphragmatic/diagnostic imaging , Hernias, Diaphragmatic, Congenital/diagnosis , Hernias, Diaphragmatic, Congenital/diagnostic imaging , Humans , Male , Radiography , Recurrence , Tomography, X-Ray Computed
11.
Phys Rev E ; 95(5-1): 052319, 2017 May.
Article in English | MEDLINE | ID: mdl-28618580

ABSTRACT

The organization of international trades is highly complex under the collective efforts towards economic profits of participating countries given inhomogeneous resources for production. Considering the trade flux as the probability of exporting a product from a country to another, we evaluate the entropy of the world trades in the period 1950-2000. The trade entropy has increased with time, and we show that it is mainly due to the extension of trade partnership. For a given number of trade partners, the mean trade entropy is about 60% of the maximum possible entropy, independent of time, which can be regarded as a characteristic of the trade fluxes' heterogeneity and is shown to be derived from the scaling and functional behaviors of the universal trade-flux distribution. The correlation and time evolution of the individual countries' gross-domestic products and the number of trade partners show that most countries achieved their economic growth partly by extending their trade relationship.

12.
Chem Sci ; 8(2): 1062-1067, 2017 Feb 01.
Article in English | MEDLINE | ID: mdl-28451245

ABSTRACT

Tumor suppressive microRNAs are potent molecules that might cure cancer, one day. Despite the many advanced strategies for delivery of these microRNAs to the cell, there are few therapeutic microRNAs in clinical use. Progress in microRNA bioapplications is hindered by a high vulnerability of exogeneous microRNA molecules to RNase degradation that occurs in extra- and intracellular physiological conditions. In this proof-of-concept study, we use a programmable self-assembled DNA nanostructure bearing a "shuriken" shape to not only deliver but more importantly protect a tumor suppressive microRNA-145 for a sufficiently long time to exert its therapeutic effect in human colorectal cancer cells. Our DNA nanostructure harbored complementary sequences that can hybridize with the microRNA cargo. This brings the microRNA-DNA duplex very close to the core structure such that the microRNA cargo becomes sterically shielded from RNase's degradative activity. Our novel DNA nanostructure based protector concept removes the degradative bottleneck that may plague other nucleic acid delivery strategies and presents a new paradigm towards exploiting these microRNAs for anti-cancer therapy.

14.
Ann Oncol ; 28(3): 628-633, 2017 03 01.
Article in English | MEDLINE | ID: mdl-28028033

ABSTRACT

Background: The relative efficacy of interventions for primary prevention of anthracycline-associated cardiotoxicity is unknown. Methods: We conducted a systematic review of randomized controlled trials for primary prevention of anthracycline-associated cardiotoxicity in adult cancer patients. We used hierarchal outcome definitions in the following order of priority: (1) composite of heart failure or decline in left ventricular ejection fraction, (2) decline in ejection fraction, or (3) heart failure. Data were analyzed using a Bayesian network meta-analysis with random effects. Results: A total of 16 trials reported cardiotoxicity as a dichotomous outcome among 1918 patients, evaluating dexrazoxane, angiotensin antagonists, beta-blockers, combination angiotensin antagonists and beta-blockers, statins, Co-enzyme Q-10, prenylamine, and N-acetylcysteine. Compared with control, dexrazoxane reduced cardiotoxicity with a pooled odds ratio (OR) of 0.26 (95% credible interval [CrI] 0.11-0.74) and had the highest probability (33%) of being most effective. No other agent was demonstrably better than placebo. Angiotensin antagonists had an 84% probability of being most effective in a sensitivity analysis excluding one outlying study (OR 0.06 [95% CrI 0.01- 0.24]). When the outcome was restricted to heart failure, dexrazoxane was associated with an OR of 0.12 (95% CrI 0.06-0.23) relative to control and had 58% probability of being most effective, while angiotensin antagonists had an OR of 0.18 (95% CrI 0.05-0.55). Available data suggested that dexrazoxane and angiotensin antagonists did not affect malignancy response rate or risk of death. Conclusion: Moderate quality data suggest that dexrazoxane, and low quality data suggest angiotensin antagonists, are likely to be effective for cardiotoxicity prevention.


Subject(s)
Anthracyclines/adverse effects , Cardiomyopathies/drug therapy , Heart Failure/drug therapy , Neoplasms/complications , Ventricular Dysfunction, Left/drug therapy , Acetylcysteine/therapeutic use , Adrenergic beta-Antagonists/therapeutic use , Angiotensins/antagonists & inhibitors , Cardiomyopathies/chemically induced , Cardiomyopathies/mortality , Cardiomyopathies/pathology , Clinical Trials as Topic , Dexrazoxane/therapeutic use , Heart Failure/chemically induced , Heart Failure/mortality , Heart Failure/pathology , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Neoplasms/drug therapy , Network Meta-Analysis , Prenylamine/therapeutic use , Ventricular Dysfunction, Left/chemically induced , Ventricular Dysfunction, Left/mortality , Ventricular Dysfunction, Left/pathology
16.
Phys Rev E ; 93(5): 052310, 2016 May.
Article in English | MEDLINE | ID: mdl-27300913

ABSTRACT

Understanding human mobility in cyberspace becomes increasingly important in this information era. While human mobility, memory-dependent and subdiffusive, is well understood in Euclidean space, it remains elusive in random heterogeneous networks like the World Wide Web. Here we study the diffusion characteristics of self-attracting walks, in which a walker is more likely to move to the locations visited previously than to unvisited ones, on scale-free networks. Under strong attraction, the number of distinct visited nodes grows linearly in time with larger coefficients in more heterogeneous networks. More interestingly, crossovers to sublinear growths occur in strongly heterogeneous networks. To understand these phenomena, we investigate the characteristic volumes and topology of the cluster of visited nodes and find that the reinforced attraction to hubs results in expediting exploration first but delaying later, as characterized by the scaling exponents that we derive. Our findings and analysis method can be useful for understanding various diffusion processes mediated by human.

17.
Colorectal Dis ; 18(7): O243-51, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27166857

ABSTRACT

AIM: The study was designed to assess the correlation between lymph node (LN) size and LN metastasis in patients with rectal neuroendocrine tumours (NETs). METHOD: Forty patients who underwent curative resection with lymphadenectomy for a rectal NET between January 2007 and December 2012 were included. The short and long diameters of entire nodes were microscopically measured using a slide gauge. RESULTS: In all, 1052 LNs were collected from the 40 patients, with 49 (4.7%) showing evidence of metastasis. Metastasis-positive LNs had significantly greater long and short diameters (P < 0.001) than metastasis-negative LNs. Of the 49 metastatic LNs, 29 (59.2%) were ≤ 5 mm in largest diameter. In five patients, the largest metastatic LN was only 2-3 mm in diameter. In clinically node-negative (cN0) patients, 18 (51.4%) patients had metastatic LNs (pN1). CONCLUSION: The size of LNs containing metastasis varied widely, with some being very small. LN size alone is therefore not a sufficient predictor of tumour metastasis in rectal NETs. Radical surgery with lymphadenectomy should be considered for patients with rectal NETs with high risk factors for LN metastasis, even those without LN enlargement.


Subject(s)
Lymph Nodes/pathology , Lymphatic Metastasis , Neuroendocrine Tumors/pathology , Rectal Neoplasms/pathology , Adult , Aged , Female , Humans , Lymph Node Excision , Lymph Nodes/surgery , Male , Middle Aged , Neuroendocrine Tumors/surgery , Rectal Neoplasms/surgery , Retrospective Studies , Risk Factors
18.
Diabetes Obes Metab ; 18(8): 795-802, 2016 08.
Article in English | MEDLINE | ID: mdl-27059951

ABSTRACT

AIMS: To assess the pharmacokinetics, pharmacodynamics, safety and tolerability of multiple ascending doses of the glucagon receptor antagonist PF-06291874 in patients with type 2 diabetes mellitus (T2DM). METHODS: Patients were randomized to oral PF-06291874 or placebo on a background of either metformin (Part A, Cohorts 1-5: 5-150 mg once daily), or metformin and sulphonylurea (Part B, Cohorts 1-2: 15 or 30 mg once daily) for 14-28 days. A mixed-meal tolerance test (MMTT) was administered on days -1 (baseline), 14 and 28. Assessments were conducted with regard to pharmacokinetics, various pharmacodynamic variables, safety and tolerability. Circulating amino acid concentrations were also measured. RESULTS: PF-06291874 exposure was approximately dose-proportional with a half-life of ∼19.7-22.7 h. Day 14 fasting plasma glucose and mean daily glucose values were reduced from baseline in a dose-dependent manner, with placebo-corrected decreases of 34.3 and 42.4 mg/dl, respectively, at the 150 mg dose. After the MMTT, dose-dependent increases in glucagon and total glucagon-like peptide-1 (GLP-1) were observed, although no meaningful changes were noted in insulin, C-peptide or active GLP-1 levels. Small dose-dependent increases in LDL cholesterol were observed, along with reversible increases in serum aminotransferases that were largely within the laboratory reference range. An increase in circulating gluconeogenic amino acids was also observed on days 2 and 14. All dose levels of PF-06291874 were well tolerated. CONCLUSION: PF-06291874 was well tolerated, has a pharmacokinetic profile suitable for once-daily dosing, and results in reductions in glucose with minimal risk of hypoglycaemia.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/administration & dosage , Pyrazoles/administration & dosage , Receptors, Glucagon/antagonists & inhibitors , beta-Alanine/analogs & derivatives , Adult , Aged , Alanine Transaminase/metabolism , Amino Acids/metabolism , Aspartate Aminotransferases/metabolism , Blood Glucose/metabolism , C-Peptide/metabolism , Cholesterol, LDL/metabolism , Diabetes Mellitus, Type 2/metabolism , Double-Blind Method , Drug Therapy, Combination , Fasting , Female , Glucagon/metabolism , Glucagon-Like Peptide 1/metabolism , Glycated Hemoglobin/metabolism , Humans , Hypoglycemic Agents/therapeutic use , Insulin/metabolism , Male , Metformin/therapeutic use , Middle Aged , Sulfonylurea Compounds/therapeutic use , beta-Alanine/administration & dosage
19.
Phys Rev E ; 93(3): 032319, 2016 Mar.
Article in English | MEDLINE | ID: mdl-27078378

ABSTRACT

Synchronizing individual activities is essential for the stable functioning of diverse complex systems. Understanding the relation between dynamic fluctuations and the connection topology of substrates is therefore important, but it remains restricted to regular lattices. Here we investigate the fluctuation of loads, assigned to the locally least-loaded nodes, in the largest-connected components of heterogeneous networks while varying their link density and degree exponents. The load fluctuation becomes finite when the link density exceeds a finite threshold in weakly heterogeneous substrates, which coincides with the spectral dimension becoming larger than 2 as in the linear diffusion model. The fluctuation, however, diverges also in strongly heterogeneous networks with the spectral dimension larger than 2. This anomalous divergence is shown to be driven by large local fluctuations at hubs and their neighbors, scaling linearly with degree, which can give rise to diverging fluctuations at small-degree nodes. Our analysis framework can be useful for understanding and controlling fluctuations in real-world systems.

20.
J Dent Res ; 95(8): 906-12, 2016 07.
Article in English | MEDLINE | ID: mdl-27013639

ABSTRACT

If there is a partial loss of dentin, the exposed dentinal surface should be protected by an indirect pulp capping (IPC) procedure to preserve pulp vitality and prevent symptoms of dentin hypersensitivity. In our previous study, copine7 (CPNE7) induced odontoblast differentiation in vitro and promoted dentin formation in vivo. The aim of this study was to investigate the possibility of IPC therapy using the CPNE7 protein at the exposed dentinal surface and the resulting effects on tertiary dentin formation in a beagle model. CPNE7 promoted mineralization of odontoblasts and had high calcium ion-binding capacity. The in vivo IPC model with canine teeth showed that regeneration of physiologic reactionary dentin with dentinal tubule structures was clearly observed beneath the remaining dentin in the CPNE7 group, whereas irregular features of reparative dentin were generated in the mineral trioxide aggregate (MTA) group. The CPNE7+MTA group also showed typical reactionary dentin without reparative dentin, showing synergistic effects of CPNE7 with MTA. A scanning electron microscopy analysis showed that dentinal tubules beneath the original dentin were occluded by the deposition of peritubular dentin in the CPNE7 and CPNE7+MTA groups, whereas those in the control group were opened. Therefore, CPNE7 may be able to serve as a novel IPC material and improve symptoms of dentin hypersensitivity.


Subject(s)
Dental Pulp Capping/methods , Dentin/growth & development , Membrane Proteins/therapeutic use , Animals , Blotting, Western , Cell Movement/drug effects , Cell Proliferation/drug effects , Cells, Cultured , Dentin/drug effects , Dogs , Humans , Odontoblasts/drug effects , Odontoblasts/physiology , Real-Time Polymerase Chain Reaction
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