Search

Importance: Systemic treatments for atopic dermatitis are being evaluated primarily in placebo-controlled trials; network meta-analysis can provide relative efficacy and safety estimates for treatments that have not been compared head to head.Objective: To compare reported measures of efficacy and assessments of safety in clinical trials of systemic treatments for atopic dermatitis in a living systematic review and network meta-analysis.Data Sources: The Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Latin American and Caribbean Health Science Information database, Global Resource of EczemA Trials database, and trial registries were searched through June 15, 2021.Study Selection: Randomized clinical trials examining 8 or more weeks of treatment with systemic immunomodulatory medications for moderate-to-severe atopic dermatitis were included after screening titles, abstracts, and papers in duplicate.Data Extraction and Synthesis: Data were abstracted in duplicate. Bayesian network meta-analyses and assessed Grading of Recommendations Assessment, Development and Evaluation certainty of evidence were performed. The updated analysis was completed from June to December 2021.Main Outcomes and Measures: Outcomes include change in Eczema Area and Severity Index (EASI), Patient Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI), and Peak Pruritus Numeric Rating Scales (PP-NRS).Results: Since October 2019, 21 new studies were added, for a total of 60 trials with 16 579 patients. Up to 16 weeks of treatment in adults, abrocitinib, 200 mg daily (mean difference [MD], 2.2; 95% credible interval [CrI], 0.2-4.0; high certainty) and upadacitinib, 30 mg daily (MD, 2.7; 95% CrI, 0.6-4.7; high certainty) were associated with reduced EASI slightly more than dupilumab, 600 mg then 300 mg every 2 weeks. Abrocitinib, 100 mg daily (MD, -2.1; 95% CrI, -4.1 to -0.3; high certainty), baricitinib, 4 mg daily (MD, -3.2; 95% CrI, -5.7 to -0.8; high certainty), baricitinib, 2 mg daily (MD, -5.2; 95% CrI, -7.5 to -2.9; high certainty) and tralokinumab, 600 mg then 300 mg every 2 weeks (MD, -3.5; 95% CrI, -5.8 to -1.3; high certainty) were associated with reduced EASI slightly less than dupilumab. There was little or no difference between upadacitinib, 15 mg daily, and dupilumab (MD, 0.2; 95% CrI, -1.9 to 2.2; high certainty). The pattern of results was similar for POEM, DLQI, and PP-NRS.Conclusions and Relevance: In this systematic review and meta-analysis, abrocitinib, 200 mg; and upadacitinib, 30 mg daily, were associated with slightly better scores than dupilumab, and upadacitinib, 15 mg daily, was associated with similar scores to dupilumab. Abrocitinib, 100 mg daily, baricitinib, 4 mg and 2 mg daily, and tralokinumab, 300 mg, every 2 weeks were associated with slightly worse scores.

Stable isotope analyses of archival specimens have revealed trophic declines over the past 150 yr in a growing number of predatory pelagic seabirds that breed in the Hawaiian Islands. However, they have not examined whether isotopic shifts occurred primarily during a specific phase of the annual cycle, which could allow us to better identify the causes of trophic declines and potential consequences for affected populations. We evaluated seasonal (breeding versus nonbreeding season) foraging habits of 2 ecologically distinct species, Newell’s shearwater Puffinus newelli and Laysan albatross Phoebastria immutabilis, and extended this analysis back 50 and 100 yr, respectively. Our assessment relied on amino acid δ15N proxies for nutrient regime use (δ15NPhe) and trophic position (Δδ15NGlu-Phe) from 2 tissues (feather and bone collagen) reflecting different time scales. Both study species exhibited season-specific isotopic shifts resulting in more pronounced seasonality in modern populations. We also identified inter-species differences in nutrient regime use, regardless of season. Laysan albatross experienced a trophic decline exclusive to the breeding season, while their nonbreeding season foraging ecology has remained constant over the past century. In contrast, the nutrient regime at the base of the food chain for Newell’s shearwaters during the nonbreeding season underwent a shift within the last 50 yr, and the trophic decline they experienced was heavily weighted toward the nonbreeding season. Efforts to mitigate potential fitness consequences of future trophic declines might benefit from focusing on fisheries management near the Hawaiian Islands, where susceptible seabirds forage during winter/spring, rather than the entire North Pacific.

In this paper, we introduce a study for the performance of intensity modulation (IM) techniques over gamma-gamma (GG) distributed free-space optical (FSO) channels. We derived closed form expressions for the average bit-error rate (BER) of thermal noise-limited FSO systems adopting various IM techniques. The effects of the atmospheric turbulence and the propagation wavelength are studied. A comparison among different IM techniques in term of transmitted peak power to achieve certain BER is presented. Results show that OOK has the best BER compared with other IM techniques. In addition, according to peak power, PPM and MPPM are more power efficient than DPPM and DMPPM, respectively.

We investigated how foraging habits vary among three ecologically distinct wide-ranging seabirds. Using amino acid δ15N proxies for nutrient regime (δ15NPhe) and trophic position (Δδ15NGlu-Phe), we compared Newell’s shearwater (Puffinus newelli) and Laysan albatross (Phoebastria immutabilis) foraging habits over the past 50–100 years, respectively, to published records for the Hawaiian petrel (Pterodroma sandwichensis). Standard ellipses constructed from the isotope proxies show that inter-population and interspecific foraging segregation have persisted for several decades. We found no evidence of a shift in nutrient regime at the base of the food web for the three species. However, our data identify a trophic decline during the past century for Newell’s shearwater and Laysan albatross (probability ≥ 0.97), echoing a similar decline observed in the Hawaiian petrel. During this time, Newell’s shearwaters and Hawaiian petrels have experienced population declines and Laysan albatross has experienced range extension and apparent population stability. Counting other recent studies, a pattern of trophic decline over the past century has now been identified in eight species of pelagic seabirds that breed in the Hawaiian Islands. Because our study species forage broadly across the North Pacific Ocean and differ in morphological and behavioral traits and feeding methods, the identified trophic declines suggest a pervasive shift in food web architecture within the past century.

The performance of the mixed millimeter-wave and radio-over-fiber (mmWave RoF) amplify-and-forward systems is studied for the fifth-generation mobile networks. The impacts of optical fiber nonlinearity, optical modulator nonlinearity, and radio frequency co-channel interference on the performance of the mixed mmWave RoF systems are included. We present the analytical results for the outage probability and the average bit-error rate in a simplified closed form expressions and verify them using Monte Carlo simulations. By careful selection of the transmit optical power in the fiber, the impacts of fiber nonlinear distortion and receiver noise can be balanced to optimize the system performance.

Studies of animal movement and migration over large geospatial scales have long relied on natural continental-scale hydrogen isotope (δ2H) gradients in precipitation, yet the physiological processes that govern incorporation of δ2H from precipitation into plant and then herbivore tissues remain poorly understood, especially at the molecular level. Establishing a biochemical framework for the propagation of δ2H through food webs would enable us to resolve more complicated regional-scale animal movements and potentially unlock new applications for δ2H data in animal ecology and eco-physiology. Amino acid δ2H analysis offers a promising new avenue by which to establish this framework. We report bulk tissue δ2H, δ13C, and δ15N data as well as amino acid δ2H and δ13C data from three Pipevine swallowtail (Battus philenor) tissues—caterpillars, butterfly bodies, and wings—as well as their obligate plant source: pipevine leaves (Aristolochia macrophylla). Insects are often dominant herbivores in terrestrial food webs and a major food source for many higher-level consumers, so it is particularly important to understand the mechanisms that influence insect tissue δ2H values. Our data reveal extensive δ2H variation within and among individuals of a relatively simple plant-herbivore system that cannot be explained by temporal or geospatial gradients of precipitation δ2H or dietary differences. Variations in essential amino acid δ2H and δ13C indicate thatB. philenoracquire these compounds from an additional source that is isotopically distinct from pipevine leaves, potentially gut microbes. We also found multiple isotopic carryover effects associated with metamorphosis. This study emphasizes the strong influence of physiology on consumer-diet δ2H discrimination in a local population of pipevines and swallowtails and provides a template that can be broadly applied to Lepidoptera—the second most diverse insect order—and other holometabolous insects. Understanding these physiological mechanisms is critical to interpreting the large degree of δ2H variation in consumer tissues often observed at a single collection site, which has implications for using δ2H isoscapes to study animal movement. Further investigation into amino acid δ2H holds promise to elucidate how subsets of amino acids may be best utilized to address specific ecological and physiological questions for which bulk tissue δ2H is insufficient.

Summary Background Tralokinumab is a fully human monoclonal antibody that specifically neutralizes interleukin‐13, a key driver of atopic dermatitis (AD). Objectives To evaluate the efficacy and safety of tralokinumab in combination with topical corticosteroids (TCS) in patients with moderate‐to‐severe AD who were candidates for systemic therapy. Methods This was a double‐blind, placebo plus TCS controlled phase III trial. Patients were randomized 2 : 1 to subcutaneous tralokinumab 300 mg or placebo every 2 weeks (Q2W) with TCS as needed over 16 weeks. Patients who achieved an Investigator’s Global Assessment (IGA) score of 0/1 and/or 75% improvement in Eczema Area and Severity Index (EASI 75) at week 16 with tralokinumab were rerandomized 1 : 1 to tralokinumab Q2W or every 4 weeks (Q4W), with TCS as needed, for another 16 weeks. Results At week 16, more patients treated with tralokinumab than with placebo achieved IGA 0/1: 38·9% vs. 26·2% [difference (95% confidence interval): 12·4% (2·9–21·9); P = 0·015] and EASI 75: 56·0% vs. 35·7% [20·2% (9·8–30·6); P, What is already known about this topic? Atopic dermatitis (AD) is a chronic interleukin (IL)‐13‐mediated disease.In clinical practice, biologics are commonly initiated as add‐on therapy to topical corticosteroids (TCS).Tralokinumab is a fully human monoclonal antibody that binds specifically to the IL‐13 cytokine with high affinity, thereby preventing receptor interaction and subsequent downstream signalling.Tralokinumab combined with TCS showed early and sustained efficacy and safety in a 12‐week, phase IIb trial in moderate‐to‐severe AD. What does this study add? This is the first phase III trial evaluating a targeted anti‐IL‐13 biologic in combination with TCS.These data demonstrate that tralokinumab plus TCS can achieve significant improvements in AD signs and symptoms and quality of life, as well as exert a steroid‐sparing effect.Response with tralokinumab in combination with TCS was maintained over 32 weeks.Tralokinumab may be considered a targeted biological treatment option for patients with moderate‐to‐severe AD. Linked Comment: Morra and Drucker. Br J Dermatol 2021; 184:386–387. Plain language summary available online

Atopic dermatitis (AD) is associated with systemic inflammation and systemic corticosteroid use which can lead to poor bone health. The aim of this systematic review is to investigate the relationship between AD and bone mineral density (BMD), osteoporosis and fractures. We searched Web of Science, Cochrane Database of Systematic Reviews, MEDLINE and Embase. Title, abstract and full-text screening, and data extraction were done in duplicate. Quality appraisal was performed using the Agency for Healthcare Research and Quality Methodology Checklist (cross-sectional studies) and Newcastle-Ottawa Scale (cohort studies). We screened 3800 abstracts and included fifteen studies (twelve cross-sectional, three cohort). In cross-sectional studies, AD was associated with decreased BMD and increased fractures. In cross-sectional studies and a cohort study, AD was associated with a higher prevalence of osteoporosis compared to controls. There was inconsistency across studies, with some finding no association. In a large cohort study, AD was associated with increased risk of fractures of the hip (HR: 1.06, 95% CI: 1.02 to 1.11), spine (HR: 1.14, 95% CI: 1.06 to 1.23) and wrist (HR: 1.06, 95% CI: 1.01 to 1.10), with further increased risk with more severe AD. Differences between studies precluded quantitative synthesis. There is some evidence supporting an association between AD and poor bone health. Research is needed to clarify this association, underlying mechanisms and develop strategies to improve bone health of individuals with AD.

Siltuximab is the only US Food and Drug Administration-approved treatment for idiopathic multicentric Castleman disease (iMCD), a rare haematological disorder associated with substantial morbidity and mortality. Although siltuximab induces a response in a significant proportion of iMCD patients via interleukin (IL)-6 neutralization, it is not universally effective. We performed an in-depth analysis of 38 baseline laboratory parameters in iMCD patients from the phase II trial of siltuximab that met criteria for treatment response or treatment failure to develop a predictive model of response. Univariate analyses identified eight baseline laboratory parameters that were significantly different between responders and treatment failures: albumin, immunoglobulin G (IgG), immunoglobulin A, C reactive protein (CRP), fibrinogen, haemoglobin, sodium and triglycerides. Stepwise logistic regression analysis of these candidate parameters identified a top performing model that included fibrinogen, IgG, haemoglobin and CRP. Based on cross-validation of the final multivariate logistic regression model, the model accurately discriminated responders from those that failed treatment (area under the receiver operator characteristic curve 0.86 [95% confidence interval: 0.73–0.95]). All four laboratory parameters associated with response to siltuximab have biological relationships with IL6 and acute inflammation. Our model suggests that iMCD patients with laboratory evidence of an inflammatory syndrome are the best candidates for siltuximab therapy.

A hybrid optical modulation approach is described, which layers a continuous wave $M$M-ary differential phase-shift keying ($M{\rm DPSK}$MDPSK) and a two-level ($2L$2L) multipulse pulse-position modulation (MPPM) intensity-modulated signal for improved spectral efficiency. These $2L$2L techniques are a generalization of earlier hybrid MPPM-$M{\rm DPSK}$MDPSK techniques and have the added advantage of reducing transmitter and detector complexities over previous hybrid modulation approaches. The spectral and power efficiencies for the proposed $2L$2L-MPPM-$M{\rm DPSK}$MDPSK modulation techniques are formulated and shown to have the highest spectral efficiency in comparison to other hybrid techniques with lower implementation complexity. The performance of the proposed $2L$2L hybrid techniques is quantified over free-space optical (FSO) networks as well as fiber networks and verified using Monte Carlo simulation. For FSO channels, the proposed $2L$2L-MPPM-$M{\rm DPSK}$MDPSK technique outperforms the traditional MPPM-$M{\rm DPSK}$MDPSK scheme by approximately 2 dB at a bit-error rate (BER) of ${10^{-4}}$10-4 and a spectral efficiency of 2.5 bit/s/Hz. Similarly, in optical fiber, the proposed scheme relaxes the impact of nonlinearity in comparison to traditional MPPM-$M{\rm DPSK}$MDPSK. Specifically, at a ${\rm BER}{=10^{-3}}$BER=10-3, the $2L$2L-MPPM-$M{\rm DPSK}$MDPSK technique outreaches the MPPM-$M{\rm DPSK}$MDPSK by 2000 km at a spectral efficiency of 2.5 bit/s/Hz and an average transmit power of $-{3}\,\,{\rm dBm}$-3dBm.

Isotope data from Hawaiian Petrel (Pterodroma sandwichensis) primaries P1 and P6 were compared to determine whether foraging habits change between the beginning and middle of the nonbreeding season. P6 data did not differ between samples derived from a longitudinal and a minimally invasive protocol and point samples taken from the feather bases. While P6 δ13C increased longitudinally, no δ15N longitudinal trends emerged, yet inter-individual δ15N variability was high. P6 δ13C data suggest that Hawaiian Petrels molt at low latitudes. Among colonies, all of which are located in the Hawaiian Islands, USA, low P6 δ15N values for Maui birds relative to Hawaii and Lanai birds reflect foraging segregation and differential utilization of 15N-enriched oceanic regions. For the Hawaiian Petrel, the isotopic similarity between P1 and P6 indicates that analogous ecological interpretations can be drawn from these feathers, and similar foraging habits persist from the beginning to middle of the nonbreeding season. Prolonged inter-colony foraging segregation may facilitate coexistence of colonies and, together with high intra-colony foraging diversity, may reduce extinction risk for the endangered Hawaiian Petrel.

A hybrid two-level multipulse pulse-position modulation-M-ary differential phase-shift keying (2L-MPPM- MDPSK) technique is proposed which achieves high power and spectral efficiencies. The proposed 2L-MPPM-MDPSK scheme is shown to have the highest spectral efficiency in comparison with other hybrid modulation schemes. Additionally, the proposed technique has the advantage of removing the complex variable delay-line required for the direct- detection of other hybrid MPPM-MDPSK systems. The performance of 2L-MPPM-MDPSK is quantified in free-space optical (FSO) channels modeled with an exponentiated Weibull (EW) fading distribution. Closed-from expressions for both bit-error rate (BER) and outage probability upper-bound are derived and verified using Monte Carlo (MC) simulation. At the same data rate and bandwidth, 2L-MPPM-MDPSK techniques outperform traditional MPPM-MDPSK scheme by approximately 2dB at a BER of 10^{−4}.

In this paper, a hybrid differential phase shift keying-multipulse pulse position modulation (DPSK–MPPM) technique is proposed in order to enhance the receiver sensitivity of optical communication systems. Both binary and quadrature formats are adopted in the proposed systems. Direct-detection DPSK schemes that are based on an asymmetric Mach–Zehnder interferometer with a novel ultrafast discrete delay unit are presented to simplify the receiver implementation. Expressions for the bit-error rate (BER) of the proposed hybrid modulation techniques are derived taking into account the effect of the optical amplifier noise. Under the constraints of the same transmitted data rate, bandwidth, and average received optical signal-to-noise ratio, the BER performances of the proposed schemes are then evaluated numerically and compared with that of traditional differential binary phase shift keying (DBPSK), differential quadrature phase shift keying (DQPSK), and MPPM schemes and with that of recent hybrid schemes. Furthermore, a comparison between the proposed systems and the traditional ones is held in terms of the bandwidth-utilization efficiency. Our results reveal that the proposed hybrid schemes are more energy-efficient and have higher receiver sensitivity compared with the traditional ones while improving the bandwidth-utilization efficiency. The proposed DPSK–MPPM system is ready to accommodate adjustable (or variable) bit rates, by virtue of the programmable delay integrated to the receiver system.

In this paper, we introduce a comprehensive study of the performance of intensity modulation (IM) techniques over gamma–gamma (GG) distributed free-space optical (FSO) channels. We derive closed-form expressions for the average bit error rate (BER) of thermal-noise-limited FSO systems adopting various IM techniques. The effect of atmospheric turbulence is studied. Comparisons are presented in terms of the transmitted peak power to achieve a certain BER. Results show that on–off keying, pulse amplitude modulation, and expurgated pulse-position modulation (EPPM) provide superior performance compared to other IM techniques. In addition, a proposal to reduce the peak-to-average power ratio (PAPR) of orthogonal frequency division multiplexing (OFDM) is introduced by adding another modulation layer of EPPM. A closed-form expression for the average BER of the proposed hybrid OFDM–EPPM technique over GG turbulent FSO channel is derived. Moreover, an expression for the outage probability of the FSO system adopting the proposed OFDM–EPPM technique is presented. Results are investigated and compared to those of traditional OFDM and hybrid OFDM with PPM (OFDM–PPM). It is shown that the hybrid OFDM–EPPM technique outperforms the hybrid OFDM–PPM technique for the same data rate. Moreover, the hybrid OFDM–EPPM technique allows higher data rates with lower PAPR values compared to those of the hybrid OFDM–PPM technique for the same number of time slots.

Objective Cancer patients and survivors are assuming active roles in decision-making and digital patient support tools are widely used to facilitate patient engagement. As part of Cancer Information Service Research Consortium's randomized controlled trials focused on the efficacy of eHealth interventions to promote informed treatment decision-making for newly diagnosed prostate and breast cancer patients, and post-treatment breast cancer, we conducted a rigorous process evaluation to examine the actual use of and perceived benefits of two complementary communication channels — print and eHealth interventions. Methods The three Virtual Cancer Information Service (V-CIS) interventions were developed through a rigorous developmental process, guided by self-regulatory theory, informed decision-making frameworks, and health communications best practices. Control arm participants received NCI print materials; experimental arm participants received the additional V-CIS patient support tool. Actual usage data from the web-based V-CIS was also obtained and reported. Results Print materials were highly used by all groups. About 60% of the experimental group reported using the V-CIS. Those who did use the V-CIS rated it highly on improvements in knowledge, patient-provider communication and decision-making. Conclusion The findings show that how patients actually use eHealth interventions either singularly or within the context of other communication channels is complex. Practice implications Integrating rigorous best practices and theoretical foundations is essential and multiple communication approaches should be considered to support patient preferences.

Background Prospective clinical trial registration serves to increase transparency and to mitigate selective reporting bias. An assessment of adult surgical trials revealed poor trial registration practice with incomplete provision of information in registries and inconsistent information in the corresponding publication. The extent and completeness of pediatric surgical trial registration are unknown. We aimed to determine the proportion and adequacy of clinical trial registration in pediatric surgery trials published in 2014. Methods Using sensitive search strategies in MEDLINE, abstracts and full-texts of prospective pediatric intervention studies published in 2014 were screened in duplicate. Pediatric surgical trials were included. Clinical trial registration numbers obtained from publications were searched in trial registries. Data were extracted based on WHO 20-item minimum data set to determine the completeness of registration data. The proportion of registered trials was recorded and registration data were compared to reported data in the corresponding publication. Results Our search and abstract screening identified 3375 articles for full text review. Following coding, a total of 54 pediatric surgical trials were included and analyzed; 28% (15/54) of which published a registration number. In trials which reported a registration number, 40% (6/15) were retrospectively registered and 40% (6/15) had made changes to their registered primary and/or secondary outcome measures. One included published trial reported an incorrect registration number. Conclusions Analysis of pediatric surgery trials published in 2014 revealed a poor prospective trial registration rate and incomplete registration data. Our study supports future initiatives for improved registration behaviors in pediatric surgery trials to ensure high-quality, transparent, reproducible evidence is generated. Study type Therapeutic (clinical trials), level II.

BACKGROUND: Vestibular Schwannoma (VS) causes loss of hearing, loss of balance, tinnitus and even may lead to facial numbness. Various treatment choices have been increasing such as surgery, fractionated stereotactic radiotherapy (FSRT), Gamma Knife radiosurgery (GKRS), single fraction linac stereotactic radiosurgery (SFSRT) and conservative treatment. However, there is no conclusive evidence about the best treatment of VS. In this study, we aimed to systematically review and meta-analyze all possible strategies for management of VS. MATERIAL AND METHODS: We conducted a systematic electronic search in 13 electronic databases; PubMed, ScienceDirect, WHO Global Health Library, Virtual Health Library (VHL), Scopus, The Institute of Science Index (ISI), Google Scholar, Clinical trials, Controlled Trials (MRCT), Cochrane, System for Information on Grey Literature in Europe (SIGLE), EMBASE, New York Academy of Medicine Grey Literature Report (NYAM) database for relevant studies. Original studies and case series reporting treatment of VS were included. Meta-analysis with random effects models was performed for the outcomes of tumor size reduction, increase in hearing capability, and complications. RESULTS: We included 48 studies including 3531 participants. The pooled proportions and 95% confidence intervals (95%-CIs) for tumor size reduction using FSRT and GKRS were 0.34 (0.20; 0.51) and 0.53 (0.40; 0.65), respectively. The proportions and 95%-CÍs of increase in hearing capability using surgery, FSRT, and GKRS were 0.11 (0.0; 0.91); 0.08 (0.05; 0.11), and 0.08 (0.05; 0.13), respectively. The pooled proportions of complications of surgery, FSRT, GKRS, and SFSRT were 0.18 (0.10; 0.30); 0.15 (0.08; 0.24); 0.21 (0.14; 0.30); and 0.32 (0.12; 0.24), respectively. CONCLUSION: Our study highlights the efficacy and safety of different treatments for VS such as surgery, FSRT, GKRS, and SFSRT. However, there are no controlled trials to compare these different remedies. Future large scale randomized controlled trials are needed to clarify.

Though the cloud radio access network (C-RAN) architecture is promising to allow for the necessary densification of radio networks in future systems, their utility relies on the availability of high-bandwidth reliable fronthaul links. In this paper, we propose a new all-optical fronthaul architecture in which user signals are forwarded over radio-over-free-space-optics (RoFSO) fronthaul that is passively coupled to an optical fiber (OF) for transport to a central office. We develop tools to plan such a network to optimize the outage probability while considering the coverage area, the density of the radio units (RUs), and the signal gain at the RUs. Each of these parameters can be designed to maintain an upperbound of the outage probability. Analytical expressions of the outage probability of the fronthaul network as well as the optimum RU gain are obtained. For a realistic design, clipping noise, atmospheric scintillation, and the effect of different weather conditions are considered for the RoFSO links, while nonlinear interference is modeled in the OF link. Given a required outage probability and density of RUs, the tools developed here can give the coverage area as well as optimum values for transmitted optical power and gain to balance the impact of all impairments.

The performance of free-space optical (FSO) communication systems adopting multipulse PPM (MPPM) techniques is investigated taking into account the effects of both the atmospheric turbulence and receiver noise. The atmospheric turbulence is modeled by a gamma-gamma distribution, which is suitable for both weak and strong turbulence. As for the receiver noise, both shot- and thermal-noise limited scenarios are considered. For the shot-noise limited system, both exact and approximate expressions of the average symbol-error rate (SER) of the system are obtained. For the thermal-noise limited system, a closed form for the upper bound of the average system SER, based on the Meijer G function, is obtained. Then, we validate it using Monte Carlo simulation results. Furthermore, we study the effects of changing the atmospheric conditions, operational wavelengths, and number of time slots on the average system performance. In addition, we compare the performance of the aforementioned system with that of the traditional PPM technique, in a gamma-gamma channel, under same constraints on the average energy per bit, transmission data rate, and bandwidth.

The authors describe 3 large randomized trials from the Cancer Information Service Research Consortium. Three web-based multimedia programs are being tested to help newly diagnosed prostate (Project 1) and breast cancer patients (Project 2) make informed treatment decisions and breast cancer patients prepare for life after treatment (Project 3). Project 3 also tests a telephone callback intervention delivered by a cancer information specialist. All participants receive standard print material specific to each project. Preliminary results from the 2-month follow-up interviews are reported for the initial wave of enrolled participants, most of whom were recruited from the Cancer Information Service (1-800-4-CANCER) telephone information program (Project 1: n =208; Project 2: n =340; Project 3: n =792). Self-reported use of the multimedia program was 51%, 52%, and 67% for Projects 1, 2, and 3, respectively. Self-reported use of the print materials (read all, most, or some) was 90%, 85%, and 83% for Projects 1, 2, and 3, respectively. The callback intervention was completed by 92% of Project 3 participants. Among those using the Cancer Information Service Research Consortium interventions, perceived usefulness and benefit was high, and more than 90% reported that they would recommend them to other cancer patients. The authors present 5 initial lessons learned that may help inform future cancer communications research.

When faced with a significant recruitment challenge for three nationwide psychoeducational trials targeting prostate and breast cancer patients, the Cancer Information Service Research Consortium initiated outreach efforts to increase accrual. Recruitment is reported by major outreach strategy to inform the use of similar campaigns, either as primary recruitment efforts or to supplement "in-reach" recruitment within oncology settings.During a 33-month period, recruitment was tracked from the National Cancer Institute's Cancer Information Service (CIS), the American Cancer Society (ACS), Dr. Susan Love Research Foundation's Love/Avon Army of Women (AOW), Internet advertising, press releases, radio/television interviews, recruitment materials in community venues, and outreach to churches and cancer support organizations.Across projects, the majority (89 %) of recruited participants (N = 2,134) was obtained from the CIS (n = 901, 19 months of recruitment), AOW (n = 869, 18 months), and ACS (n = 123, 12 months). Other efforts showed minimal gain in recruitment.Cancer information programs (e.g., CIS and ACS) and registries of individuals willing to participate in cancer-related research (e.g., AOW) can represent exceptional resources for outreach recruitment of cancer patients, especially when the eligibility criteria are highly restrictive. However, these resources do not yield samples representative of the larger population of adults diagnosed with cancer, and conclusions from such trials must be tempered accordingly.Inadequate recruitment to randomized controlled trials limits the creation of useful interventions for cancer survivors. By enrolling in cancer registries and taking part in research, cancer survivors can contribute to the development of effective resources for the survivor population.

The American Cancer Society's Health Insurance Assistance Service provides callers to its National Cancer Information Center with detailed knowledge to help them access or maintain health insurance coverage for which they might be eligible. Demographic data from April 2009 to June 2011 show that 76 % were uninsured and between the ages of 40-60; 65 % were Caucasian, 17 % African American, and 12% Hispanic; and monthly incomes were $1,999 or less. Current trends indicate that callers are similar to those identified in various health care reform publications: callers are unable to afford co-pays; facilities are requesting cash upfront; callers report loss of coverage, less adequate or less affordable coverage from employers; large out-of-pocket expense or high deductibles are needed; and modification of the CDC's Breast and Cervical Screening Program's eligibility guidelines create challenges. Six lessons that have been learned while initiating and managing this program are presented.

We investigate the power efficiency of different hybrid modulation techniques constrained to a specific spectral efficiency. Furthermore, the BER performance is compared with that of traditional schemes. It is found that, LDPSK-based hybrid techniques achieve power efficiencies near that of LQAM-based hybrid ones.

We present a scheme to encode M extra classical bits to a dense-coded pair of photons. By tuning the delay of an entangled pair of photons to one of 2^M time-bins and then applying one of the quantum dense coding protocols, a receiver equipped with a synchronized clock of reference is able to decode M bits (via classical time-bin encoding) + 2 bits (via quantum dense coding). This protocol, yet simple, does not dispense several special features of the used programmable delay apparatus to maintain the coherence of the two-photon state. While this type of time-domain encoding may be thought to be ideally of boundless photonic capacity (by increasing the number of available time-bins), errors due to the environmental noise and the imperfect devices and channel evolve with the number of time-bins., Comment: SPIE 2016

In this paper, we present a novel chaotic hybrid DPSK-MPPM modulation technique which is ultimately secure, spectrally efficient, and highly detection-sensitive. The position and phase information are perturbed by two variables of 2D chaotic map. The BER performance of the proposed scheme is then evaluated numerically and compared with that of the CPPM.

The performance of DBPSK-MPPM technique is evaluated in long-haul transmission using GN-model. The BER expression is extended to address fiber nonlinearity. Results show that fiber nonlinearity effects are more significant in DBPSK-MPPM than traditional ones.

We present a detailed analysis and computations of the emitted radiation spectrum for quantum dots (QDs) microcavity light-emitting device, where the total physical thickness of the cavity spacer was kept at 254 nm which corresponds to the wavelength of the mode number (m) = 1 resonant mode of the cavity. Our calculation gives good results for QD diameter only from 1.2 to 6.4 nm. The computations are used to examine how the emitted radiation spectrum can be optimized by varying the position of the light-emitting layer, the type of cathode material, the choice of hole transport layer material, and the thickness of electron transport layer, QD layer, and hole transport layer. These studies showed that the variation of layers geometry and the position of the light-emitting layer will optimize the output intensity and the radiation spectrum and varying the ETL and QD layer thickness will have a more effect on the emitted spectrum than varying HTL thickness. In addition, we have examined the effect of using different quantum dots sizes in emission layer. On the other hand, we have investigated the difference between the electroluminescence (EL) emissions for microcavity device in comparison with the non-cavity device, and we have found that the full width at half maximum (FWHM) of the EL is reduced from 45 nm for the QD non-cavity LED to 30 nm for the output of a resonant microcavity device. Finally, we have investigated the compatibility between our calculation and the experimental results and found a fairly good agreement between them.

A European Federation of Neurological Societies/Peripheral Nerve Society consensus guideline on the definition, investigation, and treatment of multifocal motor neuropathy (MMN) was published in 2006. The aim is to revise this guideline. Disease experts considered references retrieved from MEDLINE and Cochrane Systematic Reviews published between August 2004 and July 2009 and prepared statements that were agreed to in an iterative fashion. The Task Force agreed on Good Practice Points to define clinical and electrophysiological diagnostic criteria for MMN, investigations to be considered, and principal recommendations for treatment.

Conventional treatment of symptomatic essential thrombocythemia (ET) consists of long-term administration of myelosuppressive cytotoxic agents which, although efficacious in most cases, are associated with leukemogenic potential. Alpha-interferon (IFN) exerts a dose-dependent inhibitory influence on thrombopoiesis through a direct antiproliferative effect on megakaryocytic precursors. Therefore, it may provide a biologic, potentially non-mutagenic alternative to conventional cytotoxic treatments. At daily doses ranging from 1 to 5 M.U., alpha-IFN is efficacious in inducing a hematologic response in most patients with ET. Response to IFN is a gradual process. The median time to hematologic response varies from 1 to 3 months and a significant proportion of patients reach and maintain normal platelet counts with low doses (1–3 M.U./d). Normalization of marrow megakaryocytosis requires longer treatment (9–12 months). Also patients resistant to cytotoxic drugs may respond to alpha-IFN, suggesting a lack of cross-resistance between the two treatment modalities. Side-effects, although not severe, represents a limit to the administration of adequate doses of IFN in about 25% of cases. Once hematologic response has been obtained, both low-dose IFN and cytotoxic drugs are effective as maintenance. The full potentialities of alpha-IFN in ET in combination with cytotoxic drugs or with other cytokines need to be further investigated.

Alemtuzumab is a humanized (IgG,) rat monoclonal antibody to CD52 antigen and is currently used in the treatment of chronic lymphocytic leukemia (CLL) and other CD52-positive lymphoproliferative disorders. Various techniques have been developed to measure Alemtuzumab levels in human serum/plasma. The authors report on the validation of a very sensitive enzyme-linked immunosorbent assay (ELISA) to measure serum concentrations of the humanized IgG, using a rabbit polyclonal antibody specifically produced against the rat sequence of Alemtuzumab after papain digestion. The assay was successfully applied to test the serum samples of patients with B-lymphocyte CLL who received Alemtuzumab subcutaneously. This ELISA assay could be easily used to determine human serum levels of Alemtuzumab pre- and post-treatment to optimize dosing and scheduling and to study the relationship between dose and clinical response.

BACKGROUND: The incidence of chronic myeloid leukemia (CML) increases with age, but it is unclear how the characteristics of the disease vary with age. In children, where CML is very rare, it presents with more aggressive features, including huge splenomegaly, higher cell count and higher blast cell percentage. PATIENTS AND METHODS: To investigate if after childhood the disease maintains or loses these characteristics of aggressiveness, we analyzed 2784 adult patients, at least 18 years old, registered by GIMEMA CML WP over a 40-year period. RESULTS: Young adults (YAs: 18-29 years old) significantly differed from adults (30-59 years old) and elderly patients (at least 60 years old) particularly for the frequency of splenomegaly (71%, 63% and 55%, P < 0.001), and the greater spleen size (median value: 4.5, 3.0 and 1.0 cm, P < 0.001). According to the EUTOS score, that is age-independent, high-risk patients were more frequent among YAs, than among adult and elderly patients (18%, 9% and 6%, P < 0.001). In tyrosine kinase inhibitors-treated patients, the rates of complete cytogenetic and major molecular response were lower in YAs, and the probability of transformation was higher (16%, 5% and 7%, P = 0.011). CONCLUSIONS: The characteristics of CML or the host response to leukemia differ with age. The knowledge of these differences and of their causes may help to refine the treatment and to improve the outcome. CLINICAL TRIAL NUMBERS: NCT00510926, NCT00514488, NCT00769327, NCT00481052. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

We used intermediate doses of Ara-C (IDAra-C) in the treatment of 15 patients with chronic myelogenous leukemia (CML) in blast crisis and, combined with hydroxyurea, in 20 CML patients in accelerated phase. Patients with blastic CML received intensive 5-day courses of IDAra-C 600 mg/m2 every 12 h as a 2-h infusion. Of 15 patients, three achieved complete response (CR) and three partial response (PR), for an overall response rate of 40 per cent. All patients developed severe leukopenia and thrombocytopenia, and two died in hypoplasia. Except nausea and vomiting requiring medication, other nonhematologic toxicities were uncommon. Median response duration was 4 months (range 1 to 7 months). Survival was 5 months for responders and 1.5 months for nonresponders. Patients with CML in accelerated phase were treated with two-day courses of IDAra-C 600 mg/m2 every 12 h by 2-h infusion, every two-three weeks. Daily hydroxyurea 1-1.5 g/day was administered between courses. Of 20 patients, 15 (75 per cent) achieved a good PR with rapid improvement of the symptoms of disease acceleration. The median duration of response was 11 months (range 3 to 38 months); duration was over 24 months in five patients. The median survival from the start of IDAra-C was 13 months for responders and 3.5 months for nonresponders. We conclude that IDAra-C is an effective approach for CML in terminal phase. Its use in 5-day induction courses for blast crisis CML has a response rate comparable to that achieved with high-dose Ara-C. In patients in accelerated phase, the combination of short courses of IDAra-C with hydroxyurea is a well-tolerated treatment able to improve substantially the clinical and hematologic symptoms of disease progression.

Background. Paraprotein-associated neuropathies have heterogeneous clinical, neurophysiological, neuropathological and haematological features. Objectives. To prepare evidence-based and consensus guidelines on the clinical management of patients with both a demyelinating neuropathy and a paraprotein (paraproteinaemic demyelinating neuropathy, PDN). Methods. Search of MEDLINE and the Cochrane library, review of evidence and consensus agreement of an expert panel. Recommendations. In the absence of adequate data, evidence based recommendations were not possible but the panel agreed the following good practice points: (1) Patients with PDN should be investigated for a malignant plasma cell dyscrasia. (2) The paraprotein is more likely to be causing the neuropathy if the paraprotein is immunoglobulin (Ig)M, antibodies are present in serum or on biopsy, or the clinical phenotype is chronic distal sensory neuropathy. (3) Patients with IgM PDN usually have predominantly distal and sensory impairment, with prolonged distal motor latencies, and often anti-myelin associated glycoprotein antibodies. (4) IgM PDN sometimes responds to immune therapies. Their potential benefit should be balanced against their possible side-effects and the usually slow disease progression. (5) IgG and IgA PDN may be indistinguishable from chronic inflammatory demyelinating polyradiculoneuropathy, clinically, electrophysiologically, and in response to treatment. (6) For POEMS syndrome, local irradiation or resection of an isolated plasmacytoma, or melphalan with or without corticosteroids, should be considered, with haemato-oncology advice.

Summary. Background: VWF:RCo assay is the standard and widely used laboratory test for von Willebrand disease (VWD) diagnosis. It is hampered by high intra- and inter-assay imprecision and is time consuming. Automation may improve the assay performance and allow its routine application. Objective: Automation of VWF:RCo on the ACL 7000 coagulometer (Instrumentation Laboratory, Milan, Italy) and its evaluation in VWD diagnosis. Methods and materials: Method performance determination: precision, detection limit (DL), interferences, dose–response curve. Method comparison: analysis of 105 plasma samples from normal subjects (50), VWD type 1 (24), VWD type 2 (24) and VWD type 3 (7) with ACL VWF:RCo and comparison with the reference aggregometric (AGM) method. Results: ACL VWF:RCo: CVs around 10% vs. 19% of AGM method; DL: 0.08 U mL−1; potential interferences from bilirubin, triglycerides and hemoglobin, avoided by suitable plasma dilution; high correlation with AGM VWF:RCo (Deming regression Y =−0.0277 + 1.0519X) either in normal or VWD plasmas. In VWD types 1 and 2, the VWF:RCo/VWF:Ag ratios are >0.6 or

Self-help materials computer-tailored to the specific needs of smokers have shown promise as a high-reach, low-cost intervention for smoking cessation. Adding tailored cessation materials to telephone-based cessation counseling may be a way of generating greater efficacy in promoting and maintaining cessation. The objective of this study is to assess the efficacy of adding different types of behavioral smoking cessation materials to brief telephone-based cessation counseling.A total of 1,978 smokers calling the National Cancer Institute's (NCI's) Cancer Information Service (CIS) for help in quitting smoking initially received brief cognitive-behavioral cessation counseling from a CIS information specialist. Following a baseline interview administered by the information specialist, subjects were randomly assigned to one of four conditions, each delivered by U.S. mail: a single, untailored smoking cessation guide (SU); a single, tailored smoking cessation guide (ST); a series of four (multiple) printed materials tailored only to baseline data (MT); and a series of four (multiple) printed materials tailored to baseline as well as retailored using 5-month interim progress data (MRT). The primary outcome measure was 7-day point prevalence abstinence rates assessed using a computer-assisted telephone interview (CATI) at 12-month follow-up.At 12-month follow-up, using intent-to-treat, imputed, and per-protocol analyses, no differences were found among the four experimental conditions (linear trend), or when the ST, MT, and MRT groups were compared with the control (SU) group. Participants in the two multiple message group conditions combined (MT + MRT), however, had significantly higher abstinence rates than participants in the two single message group conditions combined (SU + ST). Moreover, among subjects who reported quitting at the 5-month follow-up, participants receiving the MRT materials reported higher abstinence rates at 12 months than the other three groups combined (SU + ST + MT). The results of this study support the effectiveness, over and above a single telecounseling interaction, of multiple tailored print material contacts on cessation. These effects, however may be due to tailoring, or the longitudinal nature of the two multiple tailored conditions, or both. The strongest evidence for tailoring occurred in the MRT condition for relapse prevention, suggesting that print materials tailored to interim progress may be especially effective in this context. The qualities of specific psychosocial and communication elements in tailored materials should receive attention in future research.

Since searching for health information is among the most popular uses of the Internet, we analyzed a survey of 6,019 callers to the National Cancer Institute's (NCI's) Cancer Information Service (CIS) to assess Internet usage and interest in technologies to access health and cancer information. Findings suggest that about 40% of CIS callers used the Internet to obtain cancer information and, of these, only about 20% found all the information they sought. Nearly 33% of Internet users called the CIS to discuss information found on the Internet; most (90%) reported that the CIS was helpful. Those who sought cancer information on the Internet were more likely to call the CIS about this information if they found all or most of the information they were seeking, compared with those who found some or little of the information. New communication services endorsed by most CIS callers included e-mails from an information specialist and telephone support from the CIS while on the Internet. The survey results indicate the importance of multiple access points, both traditional and technology based, and that there is still a need for more traditional, personalized forms of health communication. A crucial question is how best to harness and integrate these new technologies within the current generation of mediated health information systems.

The Cancer Information Service (CIS) of the National Cancer Institute (NCI) is the premiere organization for providing cancer information to the nation. The CIS provides a stellar example of how a service organization dedicated to health communications also can serve as a laboratory for research. This journey by the CIS into health communication research is described briefly, along with the current generation of research summarized in this issue of the Journal of Health Communication (JHC). The CIS model for collaborative research is presented as an exemplar that other service organizations might embrace as a strategic tool for quality improvement in health communications.

In this large randomized trial among callers to the Cancer Information Service (CIS), tailored print materials were tested for efficacy in promoting colorectal cancer (CRC) screening (fecal occult blood test [FOBT], flexible sigmoidoscopy, or colonoscopy). All participants completed baseline interviews at the end of their usual service calls to the CIS, as well as short-term (6-month) and longer-term (14-month) telephone follow-up interviews. The study sample (n = 4,014) was restricted to English-speaking CIS callers 50 + years of age, who would be eligible for CRC screening at 14 months follow-up and did not call the CIS about CRC or CRC screening. Four experimental conditions were compared: a single untailored (SU) mailout of print material (the control condition); a single tailored (ST) mailout of print material; four (multiple) tailored (MT) mailouts of print materials spanning 12 months, all of which were tailored to information obtained at baseline; and four (multiple) retailored (MRT) mailouts also spanning 12 months, with retailoring of the print materials (mailouts 2, 3, and 4) based on updated information obtained from the 6-month follow-up interviews. Consistent with the main hypothesis of this trial, a significant linear trend across the SU, ST, MT, and MRT groups was found at 14 months (42%, 44%, 51%, and 48%, respectively, p = 0.05). Only for MT was there a significant difference compared with SU (p = 0.03) for the sample as a whole, while no differences were found for MT vs. MRT at 14 months. Significant moderator effects in the predicted direction were found among females, younger participants, and among those with a history of CRC screening, all of which involved the SU vs. MT MRT comparisons. Only among younger participants (ages 50-59) was there a difference between SU vs. ST at 14 months. Given these results, we conclude from this trial the following: (1) the MRT intervention failed to show added benefit beyond the MT intervention, (2) the significant intervention effects involving the MT and MRT conditions can be explained by tailoring and/or the longitudinal nature of both interventions, and (3) the most compelling evidence in support of tailoring was found for the ST condition among younger participants, where a significant need for interventions exists at the national level. Directions for future research are discussed in light of the results summarized above.

The World Health Organization classification of myelodysplastic syndromes (MDS) is based on morphological evaluation of marrow dysplasia. We performed a systematic review of cytological and histological data from 1150 patients with peripheral blood cytopenia. We analyzed the frequency and discriminant power of single morphological abnormalities. A score to define minimal morphological criteria associated to the presence of marrow dysplasia was developed. This score showed high sensitivity/specificity (>90%), acceptable reproducibility and was independently validated. The severity of granulocytic and megakaryocytic dysplasia significantly affected survival. A close association was found between ring sideroblasts and SF3B1 mutations, and between severe granulocytic dysplasia and mutation of ASXL1, RUNX1, TP53 and SRSF2 genes. In myeloid neoplasms with fibrosis, multilineage dysplasia, hypolobulated/multinucleated megakaryocytes and increased CD34+ progenitors in the absence of JAK2, MPL and CALR gene mutations were significantly associated with a myelodysplastic phenotype. In myeloid disorders with marrow hypoplasia, granulocytic and/or megakaryocytic dysplasia, increased CD34+ progenitors and chromosomal abnormalities are consistent with a diagnosis of MDS. The proposed morphological score may be useful to evaluate the presence of dysplasia in cases without a clearly objective myelodysplastic phenotype. The integration of cytological and histological parameters improves the identification of MDS cases among myeloid disorders with fibrosis and hypocellularity.