Conservative management of women with cervical intraepithelial neoplasia grade 2 in Denmark: a cohort study.

OBJECTIVE: Assess the progression, persistence, and regression of cervical intraepithelial neoplasia grade 2 (CIN2) after new guidelines on conservative treatment, compared with previous practice. DESIGN: Nationwide register-based cohort study. SETTING: Denmark. POPULATION: Women aged 18-44 years diagnosed with CIN2 on biopsy: 6721 in 2008-2011 and 6399 in 2014-2017. METHODS: Register data were retrieved from before (2008-2011) and after (2014-2017) the introduction of new guidelines. Histology diagnoses at second visit were used to assess progression (CIN3+), persistence (CIN2), or regression (CIN1/normal). MAIN OUTCOME MEASURES: Proportion of CIN2 by type of management. Relative risk (RR) and corresponding 95% confidence intervals (95% CIs) for progression, persistence, and regression at second visit in 2014-2017, versus 2008-2011. RESULTS: The proportion of CIN2 managed conservatively increased from 29.6% in 2008-2011 to 53.3% in 2014-2017 (RR 1.81, 95% CI 1.73-1.89). Time to second visit increased by 2 months. Regression increased from 23.5 to 30.2% (RR 1.29, 95% CI 1.22-1.36), whereas persistence and progression decreased, from 42.6 to 34.9% (RR 0.82, 95% CI 0.78-0.86) and from 28.0 to 22.8% (RR 0.81, 95% CI 0.77-0.86), respectively. In 2008-2011, women managed conservatively had a regression rate of 41.8%, persistence rate of 40.9%, and progression rate of 16.6%. In 2014-2017, these rates were 46.7, 35.5, and 17.1%, respectively. CONCLUSION: After implementation of the new guidelines, conservative management became more frequent, and is now used for more than half of women with CIN2. Lesion regression became more frequent, now experienced by 47% of women managed conservatively. Similar regression rates were seen in women younger and older than 30 years, suggesting that conservative management is justifiable for women of childbearing age. TWEETABLE ABSTRACT: In Denmark, more than half of women with CIN2 are managed conservatively, and half of these women experience lesion regression.

Graft-versus-leukaemia effect post fludarabine, melphalan and alemtuzumab reduced intensity allogeneic stem cell transplantat in HIV-infected patient with acute myeloid leukaemia.

Allogeneic stem cell transplantation (Allo-HSCT) is sine qua non to cure high-risk acute myeloid leukaemia (AML). In spite the advent of highly active antiretroviral treatment, HIV-infected patients display a remarkable risk for haematological neoplasms such as non-Hodgkin lymphomas, Hodgkin lymphoma and acute leukaemia. Several case series have confirmed the efficacy of the autologous stem cell transplantation for the treatment of non-Hodgkin lymphomas in the HIV setting. Nonetheless, there is a paucity of data for the role of the Allo-HSCT in HIV-infected individuals with haematological malignancies. Herein, we presented the successful long-term outcome of a HIV-infected patient who received reduced intensity conditioned, matched unrelated donor transplant with alemtuzumab as graft-versus-host disease prophylaxis for therapy-related acute myeloid leukaemia. We propose that Allo-HSCT in HIV patients is safe and that alemtuzumab-based conditioning could further work to eradicate HIV in those whose donor is not CCR5 homozygous.

The structure of schizotypal personality traits: a cross-national study.

BACKGROUND: Schizotypal traits are considered a phenotypic-indicator of schizotypy, a latent personality organization reflecting a putative liability for psychosis. To date, no previous study has examined the comparability of factorial structures across samples originating from different countries and cultures. The main goal was to evaluate the factorial structure and reliability of the Schizotypal Personality Questionnaire (SPQ) scores by amalgamating data from studies conducted in 12 countries and across 21 sites. METHOD: The overall sample consisted of 27 001 participants (37.5% males, n = 4251 drawn from the general population). The mean age was 22.12 years (s.d. = 6.28, range 16-55 years). The SPQ was used. Confirmatory factor analysis (CFA) and Multilevel CFA (ML-CFA) were used to evaluate the factor structure underlying the SPQ scores. RESULTS: At the SPQ item level, the nine factor and second-order factor models showed adequate goodness-of-fit. At the SPQ subscale level, three- and four-factor models displayed better goodness-of-fit indices than other CFA models. ML-CFA showed that the intraclass correlation coefficients values were lower than 0.106. The three-factor model showed adequate goodness of fit indices in multilevel analysis. The ordinal α coefficients were high, ranging from 0.73 to 0.94 across individual samples, and from 0.84 to 0.91 for the combined sample. CONCLUSIONS: The results are consistent with the conceptual notion that schizotypal personality is a multifaceted construct and support the validity and utility of SPQ in cross-cultural research. We discuss theoretical and clinical implications of our results for diagnostic systems, psychosis models and cross-national mental health strategies.

Wholegrain rye, but not wholegrain wheat, lowers body weight and fat mass compared with refined wheat: a 6-week randomized study.

BACKGROUND: Observational studies suggest inverse associations between wholegrain intake and body weight gain. Only few controlled intervention studies have supported this association and few compare effects of different grain varieties. OBJECTIVE: To investigate how wholegrain wheat (WGW) and rye compared with refined wheat (RW) affect body weight and composition and appetite sensation. DESIGN: Seventy overweight/obese adults participated in this 6-week randomized parallel study, in which they replaced their habitual cereal foods with RW, WGW or wholegrain rye (WGR). Further, a 4 h postprandial test meal challenge was completed with meals corresponding to diet allocation in the beginning and after the intervention. Body weight and composition, fasted blood samples, compliance and 4-day dietary intake were obtained before and after the intervention period. Appetite and breath hydrogen excretion was assessed during the postprandial test meal challenge. RESULTS: Diet allocation affected body weight significantly (P=0.013) and tended also to affect fat mass (P=0.065). Both body weight and fat mass decreased more in the WGR group (-1.06±1.60 and -0.75±1.29 kg, respectively) compared with the RW group (+0.15±1.28 and -0.04±0.82 kg, respectively; P<0.01 and P<0.05, respectively). Further, the decrease in fat mass in the WGR group tended to exceed that in the WGW group (P=0.07). Overall, no effect of diet on appetite sensation was observed; however, energy intake from study products was ~200 kcal lower in the WGR group when compared with that in the RW group (P<0.05), although total energy intake did not differ between groups. CONCLUSIONS: Our results support a role for WGR foods in body weight regulation, when provided ad libitum. The effect may be mediated by satiation reflected in a reduction in energy intake, mainly from the wholegrain products without compensation in other parts of the diets, despite no difference in appetite.

Effect of filler geometry on coefficient of thermal expansion in carbon nanofiber reinforced epoxy composites.

This study involves the investigation of the geometry effect of nano-fillers on thermally induced dimensional stability of epoxy composites by experimentally evaluating the linear coefficient of thermal expansion (CTE). Carbon nanofibers (CNF) were chosen as the filler in epoxy matrix to investigate the effect of an aspect ratio on the CTE of the nanocomposites at three different volume fractions of 0.5, 1, and 2% of the nano-filler. The composites were fabricated using a mechanical mixing method. The CTE values were evaluated by measuring thermal strains of the composites and also compared with a micromechanics model. It was observed that the composites with short CNF (average L/d = 10) show better thermal stability than one of the composites with long CNF (average L/d = 70), and the thermal stability of the composites was proportional to the volume fraction of the filler in each composite. In addition, the CTE of mutliwalled carbon nanotubes (MWNT) reinforced epoxy composites was evaluated and compared with the CTE of the CNF reinforced composites. Interestingly, the MWNT reinforced composites show the greatest thermal stability with an 11.5% reduction in the CTE over the pure epoxy. The experimental data was compared with micromechanics model.

The relation of hydration status to declarative memory and working memory in older adults.

OBJECTIVES: Prior studies have suggested a relationship between dehydration and poor cognitive performance. The present study examined the relationships among hydration status, declarative memory and working memory skills, and blood pressure in a sample of older community dwelling females. DESIGN: Data was analyzed from a larger study; relationships among hydration status, blood pressure, and cognitive measures were assessed with correlation and meditational analyses. SETTING: Laboratory. PARTICIPANTS: 21 postmenopausal women (mean age 60.3, SD 8.03). MEASURES: Hydration status was measured using bioelectrical impedance, baseline blood pressure was assessed using a Colin Pressmate, and cognition was examined using the Auditory Verbal Learning Test and Auditory Consonant Trigrams. RESULTS: Bioelectrical impedance total body water by weight was found to be related to working memory, r = .47, p = .04, and memory skills, r = .54, p = .01. Total body water by weight was also found to be related to diastolic blood pressure, r = -.56, p = .01, which in turn was related to working memory, r = -.67, p = .002, and declarative memory, r = -.57, p = .009, skills. When diastolic blood pressure was accounted for, the relationship between hydration status and cognitive skills was attenuated. A similar pattern of results was seen for systolic blood pressure, although findings did not reach statistical significance. CONCLUSIONS: Results emphasize the importance of considering hydration status and blood pressure when interpreting cognitive performance in older adults.

Continuous carbon nanotube reinforced composites.

Carbon nanotubes are considered short fibers, and polymer composites with nanotube fillers are always analogues of random, short fiber composites. The real structural carbon fiber composites, on the other hand, always contain carbon fiber reinforcements where fibers run continuously through the composite matrix. With the recent optimization in aligned nanotube growth, samples of nanotubes in macroscopic lengths have become available, and this allows the creation of composites that are similar to the continuous fiber composites with individual nanotubes running continuously through the composite body. This allows the proper utilization of the extreme high modulus and strength predicted for nanotubes in structural composites. Here, we fabricate such continuous nanotube polymer composites with continuous nanotube reinforcements and report that under compressive loadings, the nanotube composites can generate more than an order of magnitude improvement in the longitudinal modulus (up to 3,300%) as well as damping capability (up to 2,100%). It is also observed that composites with a random distribution of nanotubes of same length and similar filler fraction provide three times less effective reinforcement in composites.

Effect of filler geometry on interfacial friction damping in polymer nanocomposites.

Single-walled carbon nanotube polycarbonate and C60 polycarbonate nanocomposites were fabricated using a solution mixing method. The composite loss modulus was characterized by application of dynamic (sinusoidal) load to the nanocomposite and the pure polymer samples. For a loading of 1 weight %, the single-walled nanotube fillers generated more than a 250% increase in loss modulus compared to the baseline (pure) polycarbonate. Even though the surface area to volume ratio and surface chemistry of C60 is similar to that for nanotubes, we report no significant increase in the energy dissipation for the 1% weight C60 nanoparticle composite compared to the pure polymer. We explain these observations by comparing qualitatively, the active sliding area (considering both normal and shear stresses) for a representative volume element of the nanotube and the nanoparticle composites. These results highlight the important role played by the filler geometry in controlling energy dissipation in nanocomposite materials.

Fatigue resistance of aligned carbon nanotube arrays under cyclic compression.

Structural components subject to cyclic stress can succumb to fatigue, causing them to fail at stress levels much lower than if they were under static mechanical loading. However, despite extensive research into the mechanical properties of carbon nanotube structures for more than a decade, data on the fatigue behaviour of such devices have never been reported. We show that under repeated high compressive strains, long, vertically aligned multiwalled nanotubes exhibit viscoelastic behaviour similar to that observed in soft-tissue membranes. Under compressive cyclic loading, the mechanical response of the nanotube arrays shows preconditioning, characteristic viscoelasticity-induced hysteresis, nonlinear elasticity and stress relaxation, and large deformations. Furthermore, no fatigue failure is observed at high strain amplitudes up to half a million cycles. This combination of soft-tissue-like behaviour and outstanding fatigue resistance suggests that properly engineered nanotube structures could mimic artificial tissues, and that their good electrical conductivity could lead to their use as compliant electrical contacts in a variety of applications.

Carbon nanotube/polycarbonate composites as multifunctional strain sensors.

In this study we demonstrate that multiwalled carbon nanotube fillers can impart a strain sensing functionality to a composite. The nanocomposite is fabricated by dispersing 5% weight of multiwalled nanotube fillers into a polycarbonate matrix. When subjected to linear and sinusoidal dynamic strain inputs, the instantaneous change in the electrical resistance (deltaR/R0) of the nanocomposite responds in a manner similar to a strain gage. The sensitivity of the nanocomposite sensor was measured to be approximately 3.5 times that of a typical strain gage. This sensitivity of the nanocomposite's electrical properties to mechanical stress implies that in addition to enhancing mechanical properties (strength, stiffness, structural damping, etc.), these multifunctional materials show the potential to provide real-time structural health monitoring and self-diagnostic functionalities.

Effect of pre-strain on interfacial friction damping in carbon nanotube polymer composites.

This paper investigates the effect of mechanical pre-strain on interfacial friction damping in nanotube polymer composites. Oxidized single-walled carbon nanotubes were dispersed in a polycarbonate matrix using a solution mixing technique. To characterize the damping response, the material storage and loss modulus was measured by application of dynamic (sinusoidal) load to the nanocomposite in the uniaxial direction. A static pre-strain (in 0.35-0.85% range) was then superimposed on the dynamic strain to quantify its effect on the material response. The results indicate that application of pre-strain facilitates the activation of interfacial slip at the nanotube-polymer interfaces at relatively low dynamic strain amplitudes. This is because pre-strain raises the interfacial shear stress for the nanotube inclusions allowing the critical stress for tube-matrix interfacial slip to be reached at lower strain amplitudes. In this way pre-strain significantly improves the effectiveness of the nanotube-matrix sliding energy dissipation mechanism for damping enhancement in composite structures.

Exaggeration index for an expanded version of the auditory verbal learning test: robustness to coaching.

Recent research suggests that effort detection measures based on patterns of neuropsychological performance may be more robust to coaching than traditional effort detection measures. In the present study, we evaluated the Exaggeration Index for an extended version of the Auditory Verbal Learning Test (EI-AVLTX), a recently developed effort detection instrument based on patterns of performance on the AVLT using a simulated malingering paradigm. In two independent samples, the EI-AVLTX was1 found to be relatively sensitive and specific to malingering, and robust to the effects of a warning about malingering detection.

[Complementary and Alternative Medicine (CAM) in Uro-Oncology]. / Komplementär- und Alternativmedizin in der Uro-Onkologie.

The West German Comprehensive Cancer Center is confronted with more than 30 000 questions per year concerning unconventional anti-cancer strategies. Unconventional or complementary drugs are not to be compared with placebos. Similar to cytotoxic drugs, unconvetional drugs have to be tested according to the guidelines of <> (GCP). An adjuvant treatment with unconventional drugs is not indicated. Because an possible immunomodulating effect, long-term results have to be considered - especially related to tumor progression. Right now a routine application of unconventional drugs is not indicated in the field of urological oncology.

[Complementary and alternative medicine in urologic oncology]. / Komplementär- und Alternativmedizin in der Uroonkologe.

The great majority of phytotherapeutic, homeopathic and anthroposophical medicines are subject to the regulations in their respective field of application, implying a simple licensing process. In contrast with conventional medications in the area of oncology, some unconventional agents are given in observation studies without the prior testing of quality, side effects and efficacy that is normal in oncology. Unconventional therapeutics cannot be considered equivalent to placebo preparations. Since they may have an immunomodulatory action, one cannot exclude possible long-term adverse effects, including progression of tumors. To date there is no clear indication for routine use of unconventional therapeutic agents in urological oncology. A scientific evaluation according to the criteria of evidence-based medicine is required. This article presents proven results of treatment with unconventional medicines in urooncology against the background of the respective spectrum of methods.

[Therapy of advanced penis carcinoma]. / Die Therapie des fortgeschrittenen Peniskarzinoms.

Skin infiltration and locoregional lymph node extension in metastatic penile cancer leads to destruction in the inguinal and perineal region. Efficacy of systemic polychemotherapy based on cisplatin, methotrexate, and bleomycin (CMB scheme) is limited with an objective remission rate up to 30% only. The obligatorily superinfected defects require tension-free and extended coverage with immediate myocutaneous flaps after surgical resection. Pedicle flaps, consisting of skin, fascia, muscle, and the supplying vessels, are used to cover the post-resection defects. In the field of surgical uro-oncology the following myocutaneous flaps listed with the supplying vessels have proved themselves: M. tensor fasciae latae flap (A. circumflexa femoris lateralis), M. rectus abdominis flap (A. epigastrica inferior), M. gluteus maximus flap (A. glutea inferior). Data concerning a prospective study for neoadjuvant chemotherapy with CMB followed by surgical tumor resection with immediate myocutaneous flap reconstruction are presented. In 15 patients (median age: 69.7 years) suffering from squamous cell carcinoma of the penis (Tx, N3, M1 cutis), a surgical excision of the tumor was performed after neoadjuvant chemotherapy (median:2.4 cycles) and antibiotic pretreatment. All patients received coverage of the femoral vessels with a musculus sartorius transfer on both sides. An extended (up to 45x30 cm) tension-free coverage of groin defects was performed in two patients with a unilateral M. tensor fasciae latae flap (TFL) and in eight patients with a bilateral TFL. One patient received a M. gluteus maximus flap (GMFL) on both sides, three patients were treated with a combination of M. rectus abdominis flap (RFL) and TFL, and one patient received a combination of two TFL, one GMFL as well as one RFL. Of 31 myocutaneous pedicle flaps, 2 developed distant necrosis of the flap, in which one GMFL and one TFL were affected. No complete necrosis of the pedicle flap occurred. Primary wound healing was found in 29 of 31 myocutaneous flaps. The covering of groin defects by the use of myocutaneous flaps, such as the M. tensor fasciae latae, M. rectus abdominis, and M. gluteus maximus flap, is a method of first choice in the primary treatment of even bacterially contaminated wounds or after radiation therapy. The techniques of pedicle flaps are comparably applied in oncology and traumatology.

[Biochips in bladder cancer research]. / Biochips in der Entwicklung für das Harnblasenkarzinom.

The techniques of DNA microarrays, protein arrays, and tissue microarrays complement one another and in the future the combination of these methods will possibly enable the detection of genes specific for bladder cancer. The SELDI technology (surface-enhanced laser desorption/ionization) will then be used to prove if the genes are translated into proteins and if those proteins have a relevant effect on the development and progression of the cancer disease. The consequence is the facilitation of the development of prognostic markers for this disease entity, which can then be easily tested in a large study population by tissue microarray. Beyond the gain of new insights into the biological understanding of the development and progression of bladder cancer, these techniques will hopefully enable the design of new therapeutic concepts, which apply to the individual biology of the tumor.

IL-18 production in human pulmonary and pleural tuberculosis.

Interleukin-18 (IL-18) has multiple important pro-inflammatory effects, including the induction of interferon-gamma (IFN-gamma) in various diseases. In this study, we investigated the IL-18-producing activities in human pulmonary and pleural tuberculosis (TB) in response to purified protein derivative (PPD) antigen (Ag) from Mycobacterium tuberculosis. The most significant IL-18 production was found in chronic refractory TB (CRTB) patients. However, IFN-gamma production in CRTB patients was significantly less than that in healthy tuberculin reactors or in patients with tuberculous pleurisy (TBP). Elevated levels of both IL-18 and IFN-gamma were found in pleural fluids from TBP patients. In vitro production of IL-18 was dramatically decreased following an 18 h stimulation with PPD. However, IFN-gamma was markedly increased in pleural mononuclear cells from TBP patients after in vitro stimulation with PPD. The mesothelial cell type was the main source of pro-IL-18 in pleural cells from TBP patients, suggesting an important role for these cells in TBP. Taken together, these data indicate that IL-18 is elevated in peripheral blood mononuclear cells from CRTB patients, as well as at the site of TBP, indicating a possible role for IL-18 in both protective immunity and pathologic responses in human TB.

Surgical treatment of disseminated peritoneal metastases from urological cancer: results from a prospective study.

OBJECTIVE: To report a prospective phase II study of patients with disseminated peritoneal carcinomatosis and symptomatic disease, in whom the peritoneal metastases were resected. PATIENTS AND METHODS: From 1995 to 1999, 32 patients (20 men and 12 women, median age 56 years, range 32-75) with peritoneal carcinomatosis were enrolled in the trial. Pain and ascites were determined according to the National Cancer Institute score/criteria, and performance scored according to the World Health Organisation criteria. RESULTS: All patients had intraperitoneal disseminated malignancies with clinically evident ascites, and presented with abdominal pain. The median (range) operative duration was 2.9 (1-5.5) h and the hospital stay 25 (10-44) days, with no deaths at 30 days. The ascites was completely cured in 25 of the 32 patients, pain relieved in 28 and the performance score improved in 25. The median survival time was 1 year; the 1- and 2-year survival rates were 45% and 38%, respectively. Patients with residual metastases after incomplete resection had a significantly worse prognosis, but the prognosis was significantly better in those with a low tumour burden. CONCLUSIONS: Peritoneal carcinomatosis is treatable; radical peritonectomy improves the performance score in selected patients with cancer-related ascites and/or pain, and is now the standard approach in the authors' Cancer Centre.

Psychological symptoms among persons 50 years of age and older living with HIV disease.

Although persons 50 years of age and older account for 10% of all US AIDS cases, the mental health needs of this growing group remain largely overlooked. The current study delineated patterns and predictors of psychological symptoms amongst late middle-aged and older adults living with HIV/AIDS in two large US cities. In late 1998, 83 HIV-infected individuals 50-plus years of age (M = 55.2, Range = 50-69) completed self-report surveys eliciting data on psychological symptomatology, HIV-related life-stressor burden, social support, barriers to health care and social services, and sociodemographic characteristics. Based on the Beck Depression Inventory, 25% of participants reported 'moderate' or 'severe' levels of depression. HIV-infected older adults also evidenced an elevated number of symptoms characteristic of somatization. A hierarchical multiple regression analysis revealed that HIV-infected older adults who endorsed more psychological symptoms also reported more HIV-related life-stressor burden, less support from friends, and reduced access to health care and social services due to AIDS-related stigma. As the impact of HIV on older communities continues to increase, geropractitioners must be prepared to provide care to greater numbers of HIV-infected older adults, a substantial minority of whom will present with complex comorbid physical and mental health conditions.

Tumor cell motility as a novel target in cancer--experimental and clinical results.

BACKGROUND: Surgery, chemotherapy and radiotherapy are the mainstay of tumor management. However, in systemic disease cure can be achieved in yet a few tumor entities. Based on cell biological research we have characterized the process of tumor progression and metastasis and disclosed that the loss of cell-cell adhesion in association with an increased tumor cell motility is an essential feature of the malignant potential of a tumor. METHODS: According to this principle we derived therapeutical methods differing from hitherto existing treatments by being exclusively focused on tumor cell motility. Characterization of so-called anti-motility factors was performed biochemically as well as with motility assays by in vitro studies in established bladder carcinoma cell lines. RESULTS: We evaluated the potential therapeutic benefit in a model of chemically induced bladder carcinoma followed by a phase I/II trial applying antimotility factors in patients with advanced bladder cancer. CONCLUSION: Both basic research as well as the results of first clinical trials confirm, that advanced carcinomas can be influenced by inhibition of tumor cell motility.