Proton Shell Gaps in N=28 Nuclei from the First Complete Spectroscopy Study with FRIB Decay Station Initiator.

The first complete measurement of the ß-decay strength distribution of _{17}^{45}Cl_{28} was performed at the Facility for Rare Isotope Beams (FRIB) with the FRIB Decay Station Initiator during the second FRIB experiment. The measurement involved the detection of neutrons and γ rays in two focal planes of the FRIB Decay Station Initiator in a single experiment for the first time. This enabled an analytical consistency in extracting the ß-decay strength distribution over the large range of excitation energies, including neutron unbound states. We observe a rapid increase in the ß-decay strength distribution above the neutron separation energy in _{18}^{45}Ar_{27}. This was interpreted to be caused by the transitioning of neutrons into protons excited across the Z=20 shell gap. The SDPF-MU interaction with reduced shell gap best reproduced the data. The measurement demonstrates a new approach that is sensitive to the proton shell gap in neutron rich nuclei according to SDPF-MU calculations.

Microsecond Isomer at the N=20 Island of Shape Inversion Observed at FRIB.

Excited-state spectroscopy from the first experiment at the Facility for Rare Isotope Beams (FRIB) is reported. A 24(2)-µs isomer was observed with the FRIB Decay Station initiator (FDSi) through a cascade of 224- and 401-keV γ rays in coincidence with ^{32}Na nuclei. This is the only known microsecond isomer (1 µs≤T_{1/2}<1 ms) in the region. This nucleus is at the heart of the N=20 island of shape inversion and is at the crossroads of the spherical shell-model, deformed shell-model, and ab initio theories. It can be represented as the coupling of a proton hole and neutron particle to ^{32}Mg, ^{32}Mg+π^{-1}+ν^{+1}. This odd-odd coupling and isomer formation provides a sensitive measure of the underlying shape degrees of freedom of ^{32}Mg, where the onset of spherical-to-deformed shape inversion begins with a low-lying deformed 2^{+} state at 885 keV and a low-lying shape-coexisting 0_{2}^{+} state at 1058 keV. We suggest two possible explanations for the 625-keV isomer in ^{32}Na: a 6^{-} spherical shape isomer that decays by E2 or a 0^{+} deformed spin isomer that decays by M2. The present results and calculations are most consistent with the latter, indicating that the low-lying states are dominated by deformation.

Fit for Duty: Lessons Learned from Outpatient and Homebound Hematopoietic Cell Transplantation to Prepare Family Caregivers for Home-Based Care.

In the past decade, the demand for home-based care has been amplified by the Coronavirus disease 2019 pandemic. Home-based care has significant benefits for patients, their families, and healthcare systems, but it relies on the often-invisible workforce of family and friend caregivers who shoulder essential health care responsibilities, frequently with inadequate training and support. Hematopoietic cell transplantation (HCT), a potentially curative but intensive treatment for many patients with blood disorders, is being increasingly offered in home-based care settings and necessitates the involvement of family caregivers for significant patient care responsibilities. However, guidelines for supporting and preparing HCT caregivers to effectively care for their loved ones at home have not yet been established. Here, informed by the literature and our collective experience as clinicians and researchers who care for diverse patients with hematologic malignancies undergoing HCT, we provide considerations and recommendations to better support and prepare family caregivers in home-based HCT and, by extension, family caregivers supporting patients with other serious illnesses at home. We suggest tangible ways to screen family caregivers for distress and care delivery challenges, educate and train them to prepare for their caregiving role, and create an infrastructure of support for family caregivers within this emerging care delivery model.

Crossing N=28 Toward the Neutron Drip Line: First Measurement of Half-Lives at FRIB.

New half-lives for exotic isotopes approaching the neutron drip-line in the vicinity of N∼28 for Z=12-15 were measured at the Facility for Rare Isotope Beams (FRIB) with the FRIB decay station initiator. The first experimental results are compared to the latest quasiparticle random phase approximation and shell-model calculations. Overall, the measured half-lives are consistent with the available theoretical descriptions and suggest a well-developed region of deformation below ^{48}Ca in the N=28 isotones. The erosion of the Z=14 subshell closure in Si is experimentally confirmed at N=28, and a reduction in the ^{38}Mg half-life is observed as compared with its isotopic neighbors, which does not seem to be predicted well based on the decay energy and deformation trends. This highlights the need for both additional data in this very exotic region, and for more advanced theoretical efforts.

Electric Monopole Transition from the Superdeformed Band in

The electric monopole (E0) transition strength ρ^{2} for the transition connecting the third 0^{+} level, a "superdeformed" band head, to the "spherical" 0^{+} ground state in doubly magic ^{40}Ca is determined via e^{+}e^{-} pair-conversion spectroscopy. The measured value ρ^{2}(E0;0_{3}^{+}→0_{1}^{+})=2.3(5)×10^{-3} is the smallest ρ^{2}(E0;0^{+}→0^{+}) found in A<50 nuclei. In contrast, the E0 transition strength to the ground state observed from the second 0^{+} state, a band head of "normal" deformation, is an order of magnitude larger ρ^{2}(E0;0_{2}^{+}→0_{1}^{+})=25.9(16)×10^{-3}, which shows significant mixing between these two states. Large-scale shell-model (LSSM) calculations are performed to understand the microscopic structure of the excited states and the configuration mixing between them; experimental ρ^{2} values in ^{40}Ca and neighboring isotopes are well reproduced by the LSSM calculations. The unusually small ρ^{2}(E0;0_{3}^{+}→0_{1}^{+}) value is due to destructive interference in the mixing of shape-coexisting structures, which are based on several different multiparticle-multihole excitations. This observation goes beyond the usual treatment of E0 strengths, where two-state shape mixing cannot result in destructive interference.

A Polymorphic Gene within the Mycobacterium smegmatis esx1 Locus Determines Mycobacterial Self-Identity and Conjugal Compatibility.

Mycobacteria mediate horizontal gene transfer (HGT) by a process called distributive conjugal transfer (DCT) that is mechanistically distinct from oriT-mediated plasmid transfer. The transfer of multiple, independent donor chromosome segments generates transconjugants with genomes that are mosaic blends of their parents. Previously, we had characterized contact-dependent conjugation between two independent isolates of Mycobacterium smegmatis. Here, we expand our analyses to include five independent isolates of M. smegmatis and establish that DCT is both active and prevalent among natural isolates of M. smegmatis. Two of these five strains were recipients but exhibited distinct conjugal compatibilities with donor strains, suggesting an ability to distinguish between potential donor partners. We determined that a single gene, Msmeg0070, was responsible for conferring mating compatibility using a combination of comparative DNA sequence analysis, bacterial genome-wide association studies (GWAS), and targeted mutagenesis. Msmeg0070 maps within the esx1 secretion locus, and we establish that it confers mycobacterial self-identity with parallels to kin recognition. Similar to other kin model systems, orthologs of Msmeg0070 are highly polymorphic. The identification of a kin recognition system in M. smegmatis reinforces the concept that communication between cells is an important checkpoint prior to DCT commitment and implies that there are likely to be other, unanticipated forms of social behaviors in mycobacteria. IMPORTANCE Conjugation, unlike other forms of HGT, requires direct interaction between two viable bacteria, which must be capable of distinguishing between mating types to allow successful DNA transfer from donor to recipient. We show that the conjugal compatibility of Mycobacterium smegmatis isolates is determined by a single, polymorphic gene located within the conserved esx1 secretion locus. This gene confers self-identity; the expression of identical Msmeg0070 proteins in both donor-recipient partners prevents DNA transfer. The presence of this polymorphic locus in many environmental mycobacteria suggests that kin identification is important in promoting beneficial gene flow between nonkin mycobacteria. Cell-cell communication, mediated by kin recognition and ESX secretion, is a key checkpoint in mycobacterial conjugation and likely plays a more global role in mycobacterial biology.

Telephone consultation for two-week-wait ENT and head and neck cancer referrals: initial evaluation including patient satisfaction.

OBJECTIVE: To analyse the outcomes of telephone consultation, including patient satisfaction, for two-week-wait head and neck cancer referrals. METHODS: Analysis of the data of this prospective study was centred on outcomes of the consultation, patient satisfaction and preference for telephone consultation. RESULTS: Patient satisfaction and preference for telephone consultation were influenced by patient awareness of cancer referral. When comparing the three most common presenting symptoms, patients with sore throat were more satisfied than those with neck mass. Regarding telephone consultation outcomes, patients with neck mass were less likely to be discharged and more likely to require investigations than those with sore throat or hoarseness. Patients with hoarseness more often required a face-to-face appointment. CONCLUSION: Telephone consultation might be a valid initial encounter for the majority of two-week-wait head and neck cancer referrals, especially when the referral symptoms are considered. This work shows the validity and safety of telephone consultation for two-week-wait head and neck cancer referrals.

Patterns of referral for fractured nose during major sporting events: a 10-year follow up.

INTRODUCTION: Nasal fracture is a common form of ear, nose and throat (ENT) trauma with prompt referral required for assessment and potentially manipulation of nasal bones. The aetiology of nasal fracture is multifactorial, and injury occurs across all ages. Previous study has suggested a temporal relationship between nasal injury and major sporting events. METHODS: A total of 1966 adult patients with nasal injuries referred to emergency clinics across three London ENT centres between September 2016 and August 2019 were analysed. RESULTS: The majority of those referred were male (66.58%). Mean age at referral was 36.29±18.38 in males and 49.14±21.43 in females; 10.27% were 75 years and over. Incidence was highest during April-September 2018 (p=0.02). Mean incidence was higher in this period in the male 16-35 subgroup (p=0.039), with 53.1% of their injuries concentrated between Friday and Sunday. CONCLUSIONS: Most nasal injuries occurred in young males. Mean age at referral was higher in females, and there was slightly increased incidence in over-75s, predominantly females. This incidence could be due to increased longevity or greater tendency to injury in females of this age. The injury patterns across the week also differed, with males injured proportionately more at the weekend. Nasal injury referrals of young men increased around the 2018 summer period, coinciding with the 2018 FIFA World Cup. This lends support to the association between major sporting events and the incidence of nasal injury, particularly in young males.

A Mycobacterial Systems Resource for the Research Community.

Functional characterization of bacterial proteins lags far behind the identification of new protein families. This is especially true for bacterial species that are more difficult to grow and genetically manipulate than model systems such as Escherichia coli and Bacillus subtilis To facilitate functional characterization of mycobacterial proteins, we have established a Mycobacterial Systems Resource (MSR) using the model organism Mycobacterium smegmatis This resource focuses specifically on 1,153 highly conserved core genes that are common to many mycobacterial species, including Mycobacterium tuberculosis, in order to provide the most relevant information and resources for the mycobacterial research community. The MSR includes both biological and bioinformatic resources. The biological resource includes (i) an expression plasmid library of 1,116 genes fused to a fluorescent protein for determining protein localization; (ii) a library of 569 precise deletions of nonessential genes; and (iii) a set of 843 CRISPR-interference (CRISPRi) plasmids specifically targeted to silence expression of essential core genes and genes for which a precise deletion was not obtained. The bioinformatic resource includes information about individual genes and a detailed assessment of protein localization. We anticipate that integration of these initial functional analyses and the availability of the biological resource will facilitate studies of these core proteins in many Mycobacterium species, including the less experimentally tractable pathogens M. abscessus, M. avium, M. kansasii, M. leprae, M. marinum, M. tuberculosis, and M. ulceransIMPORTANCE Diseases caused by mycobacterial species result in millions of deaths per year globally, and present a substantial health and economic burden, especially in immunocompromised patients. Difficulties inherent in working with mycobacterial pathogens have hampered the development and application of high-throughput genetics that can inform genome annotations and subsequent functional assays. To facilitate mycobacterial research, we have created a biological and bioinformatic resource (https://msrdb.org/) using Mycobacterium smegmatis as a model organism. The resource focuses specifically on 1,153 proteins that are highly conserved across the mycobacterial genus and, therefore, likely perform conserved mycobacterial core functions. Thus, functional insights from the MSR will apply to all mycobacterial species. We believe that the availability of this mycobacterial systems resource will accelerate research throughout the mycobacterial research community.

Early Signal of Emerging Nuclear Collectivity in Neutron-Rich

Radioactive ^{129}Sb, which can be treated as a proton plus semimagic ^{128}Sn core within the particle-core coupling scheme, was studied by Coulomb excitation. Reduced electric quadrupole transition probabilities, B(E2), for the 2^{+}⊗πg_{7/2} multiplet members and candidate πd_{5/2} state were measured. The results indicate that the total electric quadrupole strength of ^{129}Sb is a factor of 1.39(11) larger than the ^{128}Sn core, which is in stark contrast to the expectations of the empirically successful particle-core coupling scheme. Shell-model calculations performed with two different sets of nucleon-nucleon interactions suggest that this enhanced collectivity is due to constructive quadrupole coherence in the wave functions stemming from the proton-neutron residual interactions, where adding one nucleon to a core near a double-shell closure can have a pronounced effect. The enhanced electric quadrupole strength is an early signal of the emerging nuclear collectivity that becomes dominant away from the shell closure.

Integrated plasma facing component calorimetry for measurement of shot integrated deposited energy in the NSTX-U.

The upgrade to the National Spherical Torus eXperiment (NSTX-U) [J. Menard et al., Nucl. Fusion 52, 083015 (2012)] increases the injected neutral beam power up to 12 MW and the plasma current up to Ip = 2 MA for plasma durations up to 5 s. The graphite plasma facing components have been re-designed to handle greater heat and energy fluxes than were seen in NSTX using a castellated design. We present the experimental testing and validation of a castellated graphite target, similar to the prototype tile design, instrumented with thermocouples at various depths in the castellation. During testing, incident heat flux is provided by a programmed electron beam system and surface temperatures are measured via infrared thermography directly viewing the target surface. It was found that the thermocouple response scaled linearly with the measured surface temperature rise regardless of thermocouple depth in the castellation. A sensitivity of 14.3 °C/kJ of deposited energy was found when treating individual castellations as a semi-infinite solid.

Experimental tests of an infrared video bolometer on Alcator C-Mod.

A prototype of an infrared imaging bolometer (IRVB) was successfully tested on the Alcator C-Mod tokamak at the end of its 2016 campaign. The IRVB method interprets the power radiated from the plasma by measuring the temperature rise of a thin, ∼2 µm, Pt absorber that is placed in the torus vacuum and exposed, using a pinhole camera, to the full-spectrum of plasma's photon emission. The IRVB installed on C-Mod viewed the poloidal cross section of the core plasma and observed Ohmic and ion cyclotron range of frequency (ICRF)-heated plasmas. Analysis of total radiated power and on-axis emissivity from IRVB is summarized, and quantitative comparisons made to data from both resistive bolometers and AXUV diodes. IRVB results are clearly within a factor of two, but additional effort is needed for it to be used to fully support power exhaust research. The IRVB is shown to be immune to electromagnetic interference from ICRF which strongly impacts C-Mod's resistive bolometers. Results of the bench-top calibration are summarized, including a novel temperature calibration method useful for IRVBs.

Dynamics of virus-specific T cell immunity in pediatric liver transplant recipients.

Immunosuppression following solid organ transplantation (SOT) has a deleterious effect on cellular immunity leading to frequent and prolonged viral infections. To better understand the relationship between posttransplant immunosuppression and circulating virus-specific T cells, we prospectively monitored the frequency and function of T cells directed to a range of latent (CMV, EBV, HHV6, BK) and lytic (AdV) viruses in 16 children undergoing liver transplantation for up to 1 year posttransplant. Following transplant, there was an immediate decline in circulating virus-specific T cells, which recovered posttransplant, coincident with the introduction and subsequent routine tapering of immunosuppression. Furthermore, 12 of 14 infections/reactivations that occurred posttransplant were successfully controlled with immunosuppression reduction (and/or antiviral use) and in all cases we detected a temporal increase in the circulating frequency of virus-specific T cells directed against the infecting virus, which was absent in 2 cases where infections remained uncontrolled by the end of follow-up. Our study illustrates the dynamic changes in virus-specific T cells that occur in children following liver transplantation, driven both by active viral replication and modulation of immunosuppression.

Design and characterization of a prototype divertor viewing infrared video bolometer for NSTX-U.

The InfraRed Video Bolometer (IRVB) is a powerful tool to measure radiated power in magnetically confined plasmas due to its ability to obtain 2D images of plasma emission using a technique that is compatible with the fusion nuclear environment. A prototype IRVB has been developed and installed on NSTX-U to view the lower divertor. The IRVB is a pinhole camera which images radiation from the plasma onto a 2.5 µm thick, 9 × 7 cm2 Pt foil and monitors the resulting spatio-temporal temperature evolution using an IR camera. The power flux incident on the foil is calculated by solving the 2D+time heat diffusion equation, using the foil's calibrated thermal properties. An optimized, high frame rate IRVB, is quantitatively compared to results from a resistive bolometer on the bench using a modulated 405 nm laser beam with variable power density and square wave modulation from 0.2 Hz to 250 Hz. The design of the NSTX-U system and benchtop characterization are presented where signal-to-noise ratios are assessed using three different IR cameras: FLIR A655sc, FLIR A6751sc, and SBF-161. The sensitivity of the IRVB equipped with the SBF-161 camera is found to be high enough to measure radiation features in the NSTX-U lower divertor as estimated using SOLPS modeling. The optimized IRVB has a frame rate up to 50 Hz, high enough to distinguish radiation during edge-localized-modes (ELMs) from that between ELMs.

Preliminary design of a tangentially viewing imaging bolometer for NSTX-U.

The infrared imaging video bolometer (IRVB) measures plasma radiated power images using a thin metal foil. Two different designs with a tangential view of NSTX-U are made assuming a 640 × 480 (1280 × 1024) pixel, 30 (105) fps, 50 (20) mK, IR camera imaging the 9 cm × 9 cm × 2 µm Pt foil. The foil is divided into 40 × 40 (64 × 64) IRVB channels. This gives a spatial resolution of 3.4 (2.2) cm on the machine mid-plane. The noise equivalent power density of the IRVB is given as 113 (46) µW/cm2 for a time resolution of 33 (20) ms. Synthetic images derived from Scrape Off Layer Plasma Simulation data using the IRVB geometry show peak signal levels ranging from ∼0.8 to ∼80 (∼0.36 to ∼26) mW/cm2.

Variation in heterostylous breeding systems in neighbouring populations of Oxalis alpina (Oxalidaceae).

UNLABELLED: The heterostylous reproductive system of Oxalis alpina in the Galiuro Mts. of Arizona was investigated using field surveys, controlled crosses in the greenhouse and measurements of reproductive morphs. Although populations in the Pinaleño Mts. to the immediate east and in the Santa Catalina Mts. to the immediate west have derived distylous reproductive systems, tristyly, the ancestral reproductive system in O. alpina, has been retained in the Galiuro Mts. POPULATION: Tristylous incompatibility relationships in the Galiuro population are modified from the ancestral condition, with significant loss of incompatibility differentiation between stamen whorls of both short- and long-styled morphs. Morphological adjustments of anther positions in the Galiuro population of O. alpina match those expected in light of incompatibility modification, with divergence of the mid-level anthers away from the position of the mid stigmas of the mid-styled morph. The occurrence of tristyly in an area of Arizona where distyly is found in adjacent mountain ranges is particularly remarkable, and indicates both the isolation of populations restricted to the upper elevations of these mountain ranges and variation in the tempo of evolution over short geographic distances.

Fishpathogens.eu/noda: a free and handy online platform for Betanodavirus targeted research and data sharing.

Viral nervous necrosis (VNN) is a severe neuropathological disease affecting a broad variety of finfish species worldwide. The causative agents of VNN are small viruses with a bi-segmented RNA genome known as betanodaviruses. At least four species with distinct but yet insufficiently characterized epidemiological features are recognized. The spread of VNN to an increasing number of host species, its wide geographic extent and its economical and ecological impacts justify the importance of collating as much molecular data as possible for tracing the origin of viral isolates and highlight the need for a freely accessible tool for epidemiological and molecular data sharing and consultation. For this purpose, we established a web-based specific database using the www.fishpathogens.eu platform, with the aim of collecting molecular and epidemiological information on VNN viruses, with relevance to their control, management and research studies.

Evaluation of flexural, diametral tensile, and shear bond strength of composite repairs.

OBJECTIVE: Repairing composite restorations may be a more conservative treatment than replacing the entire restoration. The objective of this in vitro study was to determine the best repair method by measuring flexural, diametral tensile, and shear bond strength of repaired composites in which the surfaces were treated with chemical primers (Add & Bond or Silane Bond Enhancer), a bonding agent (Optibond Solo Plus [OBSP]), or mechanical retention with a bonding agent. METHODS: Filtek Supreme Ultra shade B1B was placed in special molds to fabricate specimens that served to test the flexural, diametral tensile, or shear strength of the inherent resin substrate. The same molds were modified to make specimens for testing repair strength of the resin. Repairs were made immediately or after aging in deionized water at 37°C for seven days. All repair sites were finished with coarse Sof-Lex discs to simulate finishing new restorations or partially removing aged restorations. Repair surfaces were treated with one of the following: 1) phosphoric-acid etching and OBSP; 2) Add & Bond; 3) phosphoric-acid etching, Silane Bond Enhancer, and OBSP; or 4) quarter round bur, phosphoric-acid etching, and OBSP. Specimens were placed back in the original molds to fabricate specimens for diametral tensile or flexural testing or in an Ultradent jig to make specimens for shear bond testing. Composite resin in shade B5B was polymerized against the treated surfaces to make repairs. Two negative control groups for the three testing methods consisted of specimens in which repairs were made immediately or after aging without any surface treatments. Controls and experimental repairs were aged (water 37°C, 24 hours) before flexural, diametral tensile, or shear testing in an Instron Universal testing machine at a crosshead speed of 0.5 mm/min. RESULTS: Experimental flexural repair strengths ranged from 26.4% to 88.6% of the inherent substrate strength. Diametral tensile repair strengths ranged from 40% to 80% of the inherent substrate strength, and shear bond strength repairs ranged from 56% to 102%. Geometric means were statistically analyzed with two-way analysis of variance on their log-transformed values. Significant differences were determined using Tukey honestly significant difference (p<0.05). CONCLUSIONS: Depending on the mechanical property being tested, surface treatments produced different results. OBSP produced more consistent results than chemical primers.

Health assessment of gasoline and fuel oxygenate vapors: developmental toxicity in mice.

CD-1 mice were exposed to baseline gasoline vapor condensate (BGVC) alone or to vapors of gasoline blended with methyl tertiary butyl ether (G/MTBE). Inhalation exposures were 6h/d on GD 5-17 at levels of 0, 2000, 10,000, and 20,000mg/m(3). Dams were evaluated for evidence of maternal toxicity, and fetuses were weighed, sexed, and evaluated for external, visceral, and skeletal anomalies. Exposure to 20,000mg/m(3) of BGVC produced slight reductions in maternal body weight/gain and decreased fetal body weight. G/MTBE exposure did not produce statistically significant maternal or developmental effects; however, two uncommon ventral wall closure defects occurred: gastroschisis (1 fetus at 10,000mg/m(3)) and ectopia cordis (1 fetus at 2000mg/m(3); 2 fetuses/1 litter at 10,000mg/m(3)). A second study (G/MTBE-2) evaluated similar exposure levels on GD 5-16 and an additional group exposed to 30,000mg/m(3) from GD 5-10. An increased incidence of cleft palate was observed at 30,000mg/m(3) G/MTBE. No ectopia cordis occurred in the replicate study, but a single observation of gastroschisis was observed at 30,000mg/m(3). The no observed adverse effect levels for maternal/developmental toxicity in the BGVC study were 10,000/2000mg/m(3), 20,000/20,000 for the G/MTBE study, and 10,000/20,000 for the G/MTBE-2 study.

Pegylated interferons Lambda-1a and alfa-2a display different gene induction and cytokine and chemokine release profiles in whole blood, human hepatocytes and peripheral blood mononuclear cells.

Pegylated interferon-lambda-1a (Lambda), a type III interferon (IFN) in clinical development for the treatment of chronic HCV infection, has shown comparable efficacy and an improved safety profile to a regimen based on pegylated IFN alfa-2a (alfa). To establish a mechanistic context for this improved profile, we investigated the ex vivo effects of Lambda and alfa on cytokine and chemokine release, and on expression of IFN-stimulated genes (ISGs) in primary human hepatocytes and peripheral blood mononuclear cells (PBMCs) from healthy subjects. Our findings were further compared with changes observed in blood analysed from HCV-infected patients treated with Lambda or alfa in clinical studies. mRNA transcript and protein expression of the IFN-λ-limiting receptor subunit was lower compared with IFN-α receptor subunits in all cell types. Upon stimulation, alfa and Lambda induced ISG expression in hepatocytes and PBMCs, although in PBMCs Lambda-induced ISG expression was modest. Furthermore, alfa and Lambda induced release of cytokines and chemokines from hepatocytes and PBMCs, although differences in their kinetics of induction were observed. In HCV-infected patients, alfa treatment induced ISG expression in whole blood after single and repeat dosing. Lambda treatment induced modest ISG expression after single dosing and showed no induction after repeat dosing. Alfa and Lambda treatment increased IP-10, iTAC, IL-6, MCP-1 and MIP-1ß levels in serum, with alfa inducing higher levels of all mediators compared with Lambda. Overall, ex vivo and in vivo induction profiles reported in this analysis strongly correlate with clinical observations of fewer related adverse events for Lambda vs those typically associated with alfa.