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1.
Article in English | MEDLINE | ID: mdl-37013726

ABSTRACT

BACKGROUND: Although primary care physicians (PCPs) play a key role in skin cancer screening, their skills in detecting malignant tumours is suboptimal. OBJECTIVES: To determine whether a short dermoscopy e-learning course (4 h) in skin tumour diagnosis for PCPs is non-inferior to a long course (12 h) in selective triage of skin lesions. Secondly, to evaluate whether regular refresher training sessions are necessary to maintain the PCPs' skills in the medium term. METHODS: A randomized 2 × 2 factorial non-inferiority trial was conducted online over an 8-month period among 233 PCPs including 126 certified general practitioners, 94 PCPs in training, and 13 occupational physicians, all without prior advanced dermoscopy training. Participants were randomized 1:1:1:1 to receive short training and mandatory refreshers (n = 58), short training and optional refreshers (n = 59), long training and mandatory refreshers (n = 58), or long training and optional refreshers (n = 58). PCPs' skills were evaluated before training (T0), immediately after training (T1) to test the non-inferiority, and after 5 months (T2) to evaluate the impact of the refreshers. The primary endpoint was the difference in the change of score after short and long training. The non-inferiority margin was set at -28%. RESULTS: Among the 233 randomized participants, 216 (93%) completed T1 and 197 (84.5%) completed T2. For short versus long training, the primary endpoint was 1.392 (95% CI: 0.138; 2.645) in the per-protocol population (p < 0.001) and 1.016 (95% CI: -0.224; 2.256) in the modified intention-to-treat population (p < 0.001). After training, the type of refresher showed no impact on the score (p = 0.840). However, PCPs who completed all refreshers showed the best mean overall score at T2 (p < 0.001). CONCLUSIONS: These findings confirm that short dermoscopy e-learning is non-inferior in training PCPs to triage skin lesions compared to long training. After training, regular refreshers are important to maintain the PCPs' acquired skills over time.

2.
Ann Dermatol Venereol ; 150(2): 95-100, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36653227

ABSTRACT

BACKGROUND: While numerous surveys over the last decade have evaluated the burden of skin diseases, none have focused on the specific impact of disease-location on the hands and face. AIM: The purpose of our study was to evaluate the burden of 8 skin diseases on the multidimensional aspects of subjects' daily lives in respect to their location on visible body areas (face or hands) versus non-visible areas. METHODS: This was a population-based study in a representative sample of the Canadian, Chinese, Italian, Spanish, German and French populations, aged over 18 years using the proportional quota sampling method. All participants were asked (i) to complete a specific questionnaire including socio-demographic characteristics, (ii) to declare if they had a skin disease. All respondents with a skin disease were asked (iii) to specify the respective disease locations (hands, face, body) and (iv) to complete the DLQI questionnaire. Respondents with 8 selected skin diseases were asked (v) to complete a questionnaire evaluating the impact of the skin disease on their daily life, including their professional activity, social relations, emotional and intimate life, leisure, sports activities and perceived stigma. RESULTS: A total of 13,138 adult participants responded to the questionnaire, of whom 26.2 % (n = 3,450) had skin diseases, and 23.4 % (n = 3,072) reported having one of the 8 selected skin diseases. Fifty-three percent were women and the mean age was 39.6 ±â€¯15.5 years. The QoL was mostly impaired when the visible localization was solely on the hands as compared with the face (38 % had a DLQI > 10 versus 22 % respectively). More subjects with a visible localization on the hands reported felt-stigma, having difficulty falling asleep and felt that their sex life had been affected. CONCLUSION: Special attention should be given to patients with skin disease on the hands and face as they are at higher risk of social exclusion and lower quality of life.


Subject(s)
Quality of Life , Skin Diseases , Adult , Humans , Female , Middle Aged , Young Adult , Male , Quality of Life/psychology , Canada , Skin Diseases/epidemiology , Surveys and Questionnaires , Social Stigma
3.
Phys Chem Chem Phys ; 23(25): 13885-13894, 2021 Jul 07.
Article in English | MEDLINE | ID: mdl-34132281

ABSTRACT

Anthracene is considered to be a popular choice as a building block for organic semiconductors. The present work is dedicated to the synthesis and characterization of a novel semiconductor (10-OPIA) possessing mesogenic properties, which allows better control over charge transport in the bulk of a material. A novel anthracene-based molecule is characterized for its potential applications: frontier molecular energy levels are studied by optical spectroscopy and cyclic voltammetry and compared to values obtained via ab initio calculations. Thermophysical and mesogenic properties are investigated by optical microscopy and differential scanning calorimetry. Charge transport properties are characterized by means of an OFET device. It is found that this material can be easily aligned and exhibits a field effect hole mobility of 5.22 × 10-5 cm2 V-1 s-1 and an ON/OFF ratio of 104 in the device prepared by drop casting. Finally, the photoconductive properties of this novel material are addressed in order to investigate its potential applications for organic phototransistors: it exhibits a large photoconductive gain of >100 and a photo-responsivity of >1 A W-1.

4.
J Eur Acad Dermatol Venereol ; 35(5): 1212-1218, 2021 May.
Article in English | MEDLINE | ID: mdl-33506539

ABSTRACT

BACKGROUND: Acne is a long-lasting disease in adolescents and adults impacting the patient's daily life. Currently, there is no specific questionnaire that assesses its impact in adult patients. AIM: To build a self-administered questionnaire assessing the impact of acne on the daily life in adult patients. METHOD: A multidisciplinary working group was created, including 3 experts in healthcare questionnaires and dermatologists specialized in acne. A questionnaire using a standardized methodology for designing self-administered patient questionnaires according to conceptual, development and validation phases was developed. A cultural and linguistic validation into US English was conducted, based on the original French version. RESULTS: A 14-item questionnaire demonstrating consistency, reproducibility and high reliability was build. The questionnaire significantly correlated with the SF-12 mental and SF-12 physical scores and CADI, indicating good external validity. CONCLUSION: The present acne burden questionnaire AI-ADL allows the practioner to assess quickly and easily the burden of acne in patients during his daily clinical practice. Moreover, its short format allows patients to express easily and quickly their feelings and to initiate a conversation between the practioner and his patient. Thus, AI-ADL may help to better understand the multidimensional nature of acne, as well as the individual impact on the acne patient's daily life and moreover, it may play a key role in the decision-making process of treatment initiation and involvement of the patient in the management of his acne.


Subject(s)
Acne Vulgaris , Quality of Life , Adolescent , Adult , Emotions , Humans , Psychometrics , Reproducibility of Results , Surveys and Questionnaires
5.
Phys Chem Chem Phys ; 21(34): 18686-18698, 2019 Aug 28.
Article in English | MEDLINE | ID: mdl-31423509

ABSTRACT

We explore the molecular nature of doping in organic semiconductors (OSCs) by employing a liquid crystalline organic semiconductor based on phenyl naphthalene as a model. The mesophase nature of composites that include a charge transfer complex (CTC) between the OSC (8-PNP-O12) and an electron acceptor (F4TCNQ) has been investigated by means of differential scanning calorimetry, polarized optical microscopy and X-ray scattering. Optical and vibrational spectroscopies allow us to explore the characteristics and the amount of charge transfer in the CTC and expose some properties that appear only in the complexed state. We have found this system to exhibit partial charge transfer, which manifests itself in all the phase states of the host 8-PNP-O12, as well as in solution. Due to the lowering of molecular symmetry as a result of the charge transfer, one of the previously IR-only vibrational bands of the nitrile group is found to be now active in the Raman spectrum. We have also made an attempt to further investigate the influence of dopant introduction on the bulk hole mobility of 8-PNP-O12. It is found that the presence of the CTC promotes the hole transport in the Smectic B mesophase, however it seems to have a somewhat negative influence in the less ordered smectic A mesophase. This work aims to establish the link between the inevitable change of molecular geometry that occurs on charge transfer with the results obtained by spectroscopic techniques and electronic charge carrier mobility measurements.

7.
Microb Ecol ; 71(4): 789-801, 2016 May.
Article in English | MEDLINE | ID: mdl-26677860

ABSTRACT

Heterotrophic bacteria are, in many aquatic systems, reliant on autochthonous organic carbon as their energy source. One exception is low-productive humic lakes, where allochthonous dissolved organic matter (ADOM) is the major driver. We hypothesized that bacterial production (BP) is similarly regulated in subarctic estuaries that receive large amounts of riverine material. BP and potential explanatory factors were measured during May-August 2011 in the subarctic Råne Estuary, northern Sweden. The highest BP was observed in spring, concomitant with the spring river-flush and the lowest rates occurred during summer when primary production (PP) peaked. PLS correlations showed that ∼60% of the BP variation was explained by different ADOM components, measured as humic substances, dissolved organic carbon (DOC) and coloured dissolved organic matter (CDOM). On average, BP was threefold higher than PP. The bioavailability of allochthonous dissolved organic carbon (ADOC) exhibited large spatial and temporal variation; however, the average value was low, ∼2%. Bioassay analysis showed that BP in the near-shore area was potentially carbon limited early in the season, while BP at seaward stations was more commonly limited by nitrogen-phosphorus. Nevertheless, the bioassay indicated that ADOC could contribute significantly to the in situ BP, ∼60%. We conclude that ADOM is a regulator of BP in the studied estuary. Thus, projected climate-induced increases in river discharge suggest that BP will increase in subarctic coastal areas during the coming century.


Subject(s)
Bacteria/growth & development , Bacteria/metabolism , Carbon/metabolism , Plankton/growth & development , Plankton/metabolism , Carbon/chemistry , North Sea , Seawater , Sweden
8.
Br J Dermatol ; 171(6): 1443-50, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25039853

ABSTRACT

BACKGROUND: Few studies about health-related quality of life (HRQoL) in patients with melanoma have expressed their results in terms of utilities or disability weights (DWs). Utilities are required for calculating quality-adjusted life years and therefore for cost-effectiveness analyses. DWs are useful to assess the burden of diseases through disability-adjusted life years. OBJECTIVES: To provide utilities and DWs regarding patients with melanoma. METHODS: The patients were classified into eight groups using four stages based on the 2009 American Joint Committee on Cancer stages, with each stage subdivided into treatment and remission phases. The EuroQoL Five Dimensions Five Levels (EQ-5D-5L) questionnaire was completed by the patients with melanoma to provide a mean utility for each group. In addition to this, the EuroQoL visual analogue scale (VAS) and a validated quality-of-life questionnaire dedicated to patients with melanoma [Functional Assessment of Cancer Therapy Melanoma (FACT-M)] were completed by the same patients in order to compare their results with the obtained utilities. DWs were obtained by calculating, for each patient, the difference between his/her utility and the corresponding sex- and age-specific population norm. RESULTS: A total of 395 questionnaire sets were completed. Utilities and DWs showed significant differences between follow-up groups. Treatment groups had similar utilities and DWs but these results were obtained during different treatment durations and therefore have different weights. The VAS and the FACT-M were found to be less sensitive. Nevertheless, the FACT-M identified some problems not found by the EQ-5D-5L questionnaire. CONCLUSIONS: The EQ-5D-5L questionnaire seems adequate to provide utilities and DWs in patients with melanoma. Lower HRQoL in female patients with melanoma is probably linked to lower HRQoL in the general population.


Subject(s)
Melanoma/psychology , Quality of Life , Skin Neoplasms/psychology , Adolescent , Adult , Aged , Aged, 80 and over , Cost of Illness , Disabled Persons , Female , Health Status , Humans , Male , Melanoma/therapy , Middle Aged , Quality-Adjusted Life Years , Skin Neoplasms/therapy , Surveys and Questionnaires , Young Adult
9.
Stat Med ; 33(30): 5265-79, 2014 Dec 30.
Article in English | MEDLINE | ID: mdl-25213096

ABSTRACT

Multicenter studies are widely used to meet accrual targets in clinical trials. Clinical data monitoring is required to ensure the quality and validity of the data gathered across centers. One approach to this end is central statistical monitoring, which aims at detecting atypical patterns in the data by means of statistical methods. In this context, we consider the simple case of a continuous variable, and we propose a detection procedure based on a linear mixed-effects model to detect location differences between each center and all other centers. We describe the performance of the procedure as a function of contamination rate and signal-to-noise ratio. We investigate the effect of center size and variance structure and illustrate the use of the procedure using data from two multicenter clinical trials.


Subject(s)
Bias , Linear Models , Multicenter Studies as Topic/methods , Signal-To-Noise Ratio , Biometry/methods , Computer Simulation , Humans , Reproducibility of Results
10.
Eur J Neurol ; 21(1): 140-6, 2014.
Article in English | MEDLINE | ID: mdl-24118277

ABSTRACT

BACKGROUND AND PURPOSE: The present study sought to determine the impact of stroke on sexual function and well-being in a cohort of young ischaemic stroke patients and identify factors associated with impairment. METHODS: Over a 2-year period, all patients aged 60 or under with ischaemic stroke or transient ischaemic attack (n = 156) were included. Information on sexual function and well-being was obtained by means of a paper questionnaire mailed to participants 1 year after their stroke. Impaired sexual activity (ISA) was defined as a decline in sexual function and/or satisfaction. Psychological well-being was evaluated on the Hospital Anxiety and Depression Scale (HADS). RESULTS: The response rate was 67% (n = 104). Thirty of these responders (29%) reported ISA. Patients with ISA had a higher HADS score (19.7 vs. 11.2 in patients with no impairment; P < 0.001), anxiety score (10.0 vs. 6.3; P < 0.001) and depression score (8.7 vs. 4.8; P < 0.001) and were more likely to have left brain lesions (70% vs. 30%; P < 0.001) and use angiotensin-converting enzyme (ACE) inhibitors (73% vs. 31%; P < 0.001) and diuretics (50% vs. 19%; P = 0.003). In a stepwise logistic regression, depression (odds ratio 9.1, 95% confidence interval 2.45-33.46; P = 0.001) and ACE inhibitor use (odds ratio 6.0, 95% confidence interval 2.11-17.28; P = 0.001) were associated with ISA. CONCLUSIONS: Impaired sexual activity was reported by almost one-third of younger patients 1 year after ischaemic stroke. Factors associated with post-stroke ISA may include specific medications and depression rather than the characteristics of the stroke per se.


Subject(s)
Sexual Behavior/statistics & numerical data , Sexual Dysfunction, Physiological/epidemiology , Sexual Dysfunction, Physiological/etiology , Stroke/complications , Adult , Cohort Studies , Female , Humans , Male , Middle Aged , Sexual Behavior/psychology , Stroke/psychology , Surveys and Questionnaires
11.
Br J Dermatol ; 167(4): 778-86, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22564185

ABSTRACT

BACKGROUND: Digital dermoscopy has been shown to permit an earlier detection of melanoma. However, few studies have investigated its added value in reducing unnecessary excisions in everyday clinical practice. OBJECTIVES: To compare, in daily practice, the efficiency of three dermoscopy methods: dermoscopy alone with little training, dermoscopy alone with adequate training and dermoscopy with adequate training and access to digital dermoscopy, and to confirm the safety of this latter approach. METHODS: Thirty-six dermatologists working without digital dermoscopy were divided into two groups according to their training in dermoscopy. The third group constituted of two dermatologists working in a pigmented lesion clinic with access to the digital dermoscopy technique and eight additional dermatologists working in the same dermatology department. These 46 dermatologists included all presumed melanocytic lesions excised over a period of 1 year. The primary endpoint was the melanoma/nonmelanoma ratio (M/NM-R); secondary endpoints were the ratio of 'problem' naevi to common naevi (PN/CN-R), specificity and sensitivity for the diagnosis of melanoma, in situ/invasive melanoma ratio, and the mean Breslow thickness. RESULTS: In total, 1865 excised lesions, including 231 melanomas, were included. In the digital dermoscopy availability group (DD-G) the M/NM-R was significantly better (1/2.43), as was the PN/CN-R (1/1.48) (P < 0.001 in both cases). The specificity was significantly higher in the DD-G and significantly higher for trained examiners as compared with examiners with little training. More that one-third of all melanomas discovered by digital dermoscopy were in situ, and the mean Breslow thickness was 0.32 mm for the invasive ones. CONCLUSIONS: The reduction of unnecessary excisions when using digital dermoscopy compared with dermoscopy alone in our study suggests that access to digital dermoscopy offers a better management of pigmented lesions in daily practice. The high number of early lesions diagnosed by this technique confirms that its use is safe.


Subject(s)
Dermoscopy/methods , Melanoma/diagnosis , Nevus, Pigmented/diagnosis , Skin Neoplasms/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Dermoscopy/standards , Early Detection of Cancer/methods , Education, Medical, Continuing , Female , Humans , Image Interpretation, Computer-Assisted/methods , Image Interpretation, Computer-Assisted/standards , Male , Melanocytes , Melanoma/surgery , Middle Aged , Nevus, Pigmented/surgery , Risk Factors , Sensitivity and Specificity , Skin Neoplasms/surgery , Young Adult
12.
Oncology ; 78(3-4): 267-70, 2010.
Article in English | MEDLINE | ID: mdl-20523087

ABSTRACT

PURPOSE: Carboplatin area under the curve (AUC) 5 ml/min on day 1 with gemcitabine 1,250 mg/m(2) on day 1 and day 8 is a widely used regimen in advanced non-small cell lung cancer. Grade 3-4 thrombocytopenia and neutropenia are frequent. The aim of this study is to investigate whether toxicity of gemcitabine/carboplatin could be reduced by administering carboplatin on day 8 instead of day 1 without a decrease in response rate (RR). METHODS: Patients received gemcitabine 1,250 mg/m(2) on days 1 and 8, carboplatin AUC 5 on day 1 (arm A) or day 8 (arm B). Drugs were administered over a 21-day cycle. Toxicity and RR were evaluated weekly and every second cycle, respectively. RESULTS: 71 patients were enrolled into the study. We found 79% (95% CI 61-91%) grade 3-4 toxicity (neutropenia and thrombocytopenia) in arm A and 50% (95% CI 32-68%) in arm B; 66% grade 3-4 thrombocytopenia in arm A and 26% in arm B. We observed 30% grade 4 hematological toxicity in arm A and 3% in arm B. In arm A an overall RR of 20% (95% CI 7.7-38.6%) was seen, and 18.2% (95% CI 7-35.5%) in arm B. CONCLUSIONS: Although the study was prematurely closed, the current data are of interest. The schedule with carboplatin on day 8 is associated with substantially lower grade 3-4 neutropenia and thrombocytopenia with comparable dose intensity and RR.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carboplatin/administration & dosage , Carcinoma, Non-Small-Cell Lung/drug therapy , Deoxycytidine/analogs & derivatives , Drug Administration Schedule , Lung Neoplasms/drug therapy , Adult , Aged , Area Under Curve , Deoxycytidine/administration & dosage , Female , Humans , Male , Middle Aged , Neutropenia/etiology , Thrombocytopenia/etiology , Treatment Outcome , Gemcitabine
13.
Eur Phys J E Soft Matter ; 33(4): 335-42, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21107879

ABSTRACT

Linear and non-linear dielectric measurements were carried out on a ferroelectric liquid crystal stabilized by an anisotropic polymer network. The polymerization process was achieved at room temperature. It was performed from an achiral monomer in the ferroelectric chiral smectic C phase, exhibiting a very short helical pitch and a large polarization. The linear and non-linear dielectric spectroscopy were also completed by textural morphology as well as structural and ferroelectric characterizations. All these measurements were carried out on a pure ferroelectric liquid crystal material and on composite films containing two polymer concentrations. The increase of the polymer network density leads to a decrease of the dielectric strength determined in the linear and non-linear dielectric spectroscopy. The complementarity between the linear and non-linear dielectric measurements and their confrontation with a theoretical model allowed the simultaneous determination of some physical parameters such as macroscopic polarization, rotational viscosity and twist elastic energy. We also discuss the effect of the polymer network density on the obtained physical parameters.


Subject(s)
Ferric Compounds/chemistry , Liquid Crystals/chemistry , Polymers/chemistry , Algorithms , Elasticity , Electric Conductivity , Microscopy, Polarization , Molecular Dynamics Simulation , Temperature , Viscosity
14.
J Cell Biol ; 146(2): 517-29, 1999 Jul 26.
Article in English | MEDLINE | ID: mdl-10427102

ABSTRACT

Cell spreading and migration associated with the expression of the 92-kD gelatinase (matrix metalloproteinase 9 or MMP-9) are important mechanisms involved in the repair of the respiratory epithelium. We investigated the location of MMP-9 and its potential role in migrating human bronchial epithelial cells (HBEC). In vivo and in vitro, MMP-9 accumulated in migrating HBEC located at the leading edge of a wound and MMP-9 expression paralleled cell migration speed. MMP-9 accumulated through an actin-dependent pathway in the advancing lamellipodia of migrating cells and was subsequently found active in the extracellular matrix (ECM). Lamellipodia became anchored through primordial contacts established with type IV collagen. MMP-9 became amassed behind collagen IV where there were fewer cell-ECM contacts. Both collagen IV and MMP-9 were involved in cell migration because when cell-collagen IV interaction was blocked, cells spread slightly but did not migrate; and when MMP-9 activation was prevented, cells remained fixed on primordial contacts and did not advance at all. These observations suggest that MMP-9 controls the migration of repairing HBEC by remodeling the provisional ECM implicated in primordial contacts.


Subject(s)
Bronchi/cytology , Cell Movement , Collagenases/metabolism , Epithelial Cells/cytology , Extracellular Matrix/metabolism , Actins/metabolism , Antibodies, Monoclonal/pharmacology , Cell Adhesion/drug effects , Cell Movement/drug effects , Cell Size/drug effects , Cells, Cultured , Collagen/immunology , Collagen/metabolism , Collagenases/immunology , Cytochalasin B/pharmacology , Enzyme Activation , Epithelial Cells/drug effects , Epithelial Cells/enzymology , Epithelial Cells/metabolism , Humans , Intercellular Junctions/drug effects , Intercellular Junctions/metabolism , Kinetics , Matrix Metalloproteinase 9 , Matrix Metalloproteinase Inhibitors , Microscopy, Video , Models, Biological , Phenylalanine/analogs & derivatives , Phenylalanine/pharmacology , Pseudopodia/drug effects , Pseudopodia/enzymology , Pseudopodia/metabolism , Thiophenes/pharmacology , Vinculin/metabolism , Wound Healing/drug effects
15.
J Clin Invest ; 79(3): 962-9, 1987 Mar.
Article in English | MEDLINE | ID: mdl-3818957

ABSTRACT

Patient C.M. presented platelet function defects symptomatic of Glanzmann's thrombasthenia. However, analysis of surface-labeled platelets by SDS-polyacrylamide gel electrophoresis revealed the usual presence of the major glycoproteins, including GP IIb and GP IIIa. Platelet fibrinogen was not detected. Analysis of Triton X-100 extracts of Ca2+-washed C.M. platelets by crossed immunoelectrophoresis (CIE) showed normal amounts of GP IIb-IIIa complexes. However, when samples were electrophoresed through an agarose gel containing 125I-fibrinogen, the usual binding of fibrinogen to GP IIb-IIIa did not occur. Furthermore, the GP IIb-IIIa complexes showed an increased sensitivity to dissociation with EDTA, either after Triton X-100 solubilization or in the intact platelet membrane. For example, after incubation with EDTA at room temperature, the patient's platelets bound little of the monoclonal antibodies AP-2 or T10 (anti-GP IIb-IIIa complex) although normally binding Tab (anti-GP IIb). Patient C.M. appears to represent a subgroup of thrombasthenia where platelets contain unstable GP IIb-IIIa complexes unable to support fibrinogen binding.


Subject(s)
Blood Platelet Disorders/blood , Blood Platelets/physiology , Platelet Membrane Glycoproteins/blood , Thrombasthenia/blood , Adult , Antibodies, Monoclonal/immunology , Binding Sites, Antibody , Blood Platelets/immunology , Cell Membrane/immunology , Cell Membrane/metabolism , Electrophoresis, Polyacrylamide Gel , Female , Fibrinogen/metabolism , Humans , Immunoelectrophoresis, Two-Dimensional
16.
J Clin Invest ; 91(4): 1637-43, 1993 Apr.
Article in English | MEDLINE | ID: mdl-8473507

ABSTRACT

The molecular defect in the abnormal fibrinogen Dusart (Paris V) that is associated with thrombophilia was determined by sequence analysis of genomic DNA that had been amplified using the polymerase chain reaction. The propositus was heterozygous for a single base change (C-->T) in the A alpha-chain gene, resulting in the amino acid substitution A alpha 554 Arg-->Cys. Restriction analysis of the amplified DNA derived from the family members showed that his father and his two sons were also heterozygous. Electron microscopic studies on fibrin formed from purified fibrinogen Dusart demonstrated fibers that were much thinner than in normal fibrin. In contrast to the previously observed defective binding of plasminogen, the binding of thrombospondin to immobilized fibrinogen Dusart was similar to that of normal fibrinogen. Immunoblot analysis of plasma fibrinogen demonstrated that a substantial part of the fibrinogen Dusart molecules were disulfide-linked to albumin. The plasma of the affected family members also contained fibrinogen-albumin complexes. Furthermore, small amounts of high molecular weight complexes containing fibrinogen were detected in all the heterozygous individuals. These data indicate that the molecular abnormality in fibrinogen Dusart (A alpha 554 Arg-->Cys) results in defective lateral association of the fibrin fibers and disulfide-linked complex formation with albumin, and is associated with a family history of recurrent thrombosis in the affected individuals.


Subject(s)
Fibrinogens, Abnormal/chemistry , Thrombosis/genetics , Adult , Base Sequence , Blood Coagulation Disorders/genetics , Fibrin/ultrastructure , Fibrinogen/metabolism , Fibrinogens, Abnormal/genetics , Gene Amplification , Humans , Immunoblotting , Male , Microscopy, Electron , Molecular Sequence Data , Mutation , Platelet Membrane Glycoproteins/metabolism , Protein Binding , Sequence Analysis, DNA , Structure-Activity Relationship , Sulfhydryl Compounds/analysis , Thrombosis/metabolism , Thrombospondins
17.
Lung Cancer ; 55(1): 95-9, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17069931

ABSTRACT

The present EORTC phase II feasibility study in stage IIIB (T4-N3) NSCLC was conducted to investigate whether an induction regimen with concurrent chemoradiotherapy followed by surgery after restaging by re-mediastinoscopy and/or fluorodeoxyglucose-positron emission tomography (FDG-PET) was feasible in a multicenter setting. Unfortunately, the study closed prematurely because of poor accrual. The combination of more stringent selection criteria, the incorrect prevailing view of Ethical Boards that a tri-modality approach is too toxic, competing studies in the participating centers and the fact that patients with N3 disease could only be enrolled if a re-mediastinoscopy could be performed, underlie the low accrual. Although this study illustrates that the conduct of a tri-modality study across Europe appeared to be difficult at that time, the number of centers with highly qualified and experienced specialists involved in this kind of multi-modality approaches is rapidly increasing. Future initiatives should, therefore, certainly be encouraged. Minimally invasive procedures such as EUS and EBUS should preferably be used for up-front mediastinal staging, mediastinoscopy with or without EUS should preferably be reserved for restaging, and especially right-sided pneumonectomies should be avoided. Though evident, the feasibility to complete this kind of studies within a reasonable time period is still a condition sine qua non.


Subject(s)
Carcinoma, Non-Small-Cell Lung/surgery , Lung Neoplasms/surgery , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/radiotherapy , Clinical Trials, Phase III as Topic , Combined Modality Therapy , Fluorodeoxyglucose F18 , Humans , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Lung Neoplasms/radiotherapy , Neoplasm Staging , Positron-Emission Tomography , Radiopharmaceuticals , Treatment Outcome
18.
J Phys Condens Matter ; 19(29): 296203, 2007 Jul 25.
Article in English | MEDLINE | ID: mdl-21483074

ABSTRACT

We report structural (helical pitch), electro-optical (tilt angle and spontaneous polarization) and dielectric (Goldstone mode) investigations of ferroelectric liquid crystals (FLCs) exhibiting the chiral smectic C phase (SmC(*)). All these characterizations were performed on two pure FLCs showing the SmC(*)-SmA-N(*) phase sequence and having small pitch, high spontaneous polarization and a large relaxation frequency. We have determined the Goldstone rotational viscosity and the twist elastic constant in the SmC(*) phase from the helical pitch, tilt angle, polarization, dielectric strength experimental data and from the relaxation frequency of the Goldstone-mode relaxation. An Arrhenius-type behaviour of the Goldstone rotational viscosity was obtained and the corresponding activation energies were evaluated.

19.
Lymphology ; 40(1): 26-34, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17539462

ABSTRACT

We conducted a reliability comparison study to determine the intrarater and inter-rater reliability and the limits of agreement of the volume estimated by circumferential measurements using the frustum sign method and the disk model method, by water displacement volumetry, and by infrared optoelectronic volumetry in the assessment of upper limb lymphedema. Thirty women with lymphedema following axillary lymph node dissection surgery for breast cancer surgery were enrolled. In each patient, the volumes of the upper limbs were estimated by three physical therapists using circumference measurements, water displacement and optoelectronic volumetry. One of the physical therapists performed each measure twice. Intraclass correlation coefficients (ICCs), relative differences, and limits of agreement were determined. Intrarater and interrater reliability ICCs ranged from 0.94 to 1. Intrarater relative differences were 1.9% for the disk model method, 3.2% for the frustum sign model method, 2.9% for water displacement volumetry, and 1.5% for optoelectronic volumetry. Intrarater reliability was always better than interrater, except for the optoelectronic method. Intrarater and interrater limits of agreement were calculated for each technique. The disk model method and optoelectronic volumetry had better reliability than the frustum sign method and water displacement volumetry, which is usually considered to be the gold standard. In terms of low-cost, simplicity, and reliability, we recommend the disk model method as the method of choice in clinical practice. Since intrarater reliability was always better than interrater reliability (except for optoelectronic volumetry), patients should therefore, ideally, always be evaluated by the same therapist. Additionally, the limits of agreement must be taken into account when determining the response of a patient to treatment.


Subject(s)
Anthropometry/methods , Lymphedema/diagnosis , Upper Extremity/pathology , Water , Aged , Axilla , Body Composition , Breast Neoplasms/surgery , Chronic Disease , Electric Impedance , Female , Humans , Lymph Node Excision/adverse effects , Lymphedema/epidemiology , Lymphedema/etiology , Lymphedema/pathology , Mastectomy, Segmental/adverse effects , Mastectomy, Simple/adverse effects , Middle Aged , Models, Biological , Observer Variation , Reproducibility of Results , Research Design , Treatment Outcome
20.
J Plankton Res ; 39(1): 23-34, 2017 Jan.
Article in English | MEDLINE | ID: mdl-28566797

ABSTRACT

It is well-known that nutrients shape phytoplankton communities in marine systems, but in coastal waters allochthonous dissolved organic matter (ADOM) may also be of central importance. We studied how humic substances (proxy of ADOM) and other variables influenced the nutritional strategies, size structure and pigment content of the phytoplankton community along a south-north gradient in the Baltic Sea. During the summer, the proportion of mixotrophs increased gradually from the phosphorus-rich south to the ADOM-rich north, probably due to ADOM-fueled microbes. The opposite trend was observed for autotrophs. The chlorophyll a (Chl a): carbon (C) ratio increased while the levels of photoprotective pigments decreased from south to north, indicating adaptation to the darker humic-rich water in the north. Picocyanobacteria dominated in phosphorus-rich areas while nanoplankton increased in ADOM-rich areas. During the winter-spring the phytoplankton biomass and concentrations of photoprotective pigments were low, and no trends with respect to autotrophs and mixotrophs were observed. Microplankton was the dominant size group in the entire study area. We conclude that changes in the size structure of the phytoplankton community, the Chl a:C ratio and the concentrations of photoprotective pigments are indicative of changes in ADOM, a factor of particular importance in a changing climate.

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