Spin Polarons and Ferromagnetism in Doped Dilute Moiré-Mott Insulators.

Moiré heterostructures of transition metal dichalcogenides (TMDs) exhibit Mott-insulating behavior both at half filling as well as at fractional fillings, where electronic degrees of freedom form self-organized Wigner crystal states. An open question concerns magnetic states obtained by lifting the pseudospin-1/2 degeneracy of these states at lowest temperatures. While at half filling virtual hopping is expected to induce (weak) antiferromagnetic exchange interactions, these are strongly suppressed when considering dilute filling fractions. We argue that, instead, a small concentration of doped electrons leads to the formation of spin polarons, inducing ferromagnetic order at experimentally relevant temperatures, consistent with recently observed ferromagnetic states in moiré TMD systems. We predict explicit signatures of polaron formation in the magnetization profile.

Adjusting the RAPID score with 2 additional variables significantly increases its predictive value in patients with empyema.

Pleural empyema is a serious condition leading to a significant burden on health care systems due to protracted hospitalisations. Treatment ranges from non-surgical interventions such as antibiotic therapy and chest tube placement to thoracoscopic or open surgery. Various risk factors which impact outcomes have been investigated. The RAPID (renal, age, purulence, infection source, and dietary factors) score is a clinical risk score which identifies patients at risk of death and may be used to formulate individual treatment strategies accordingly. All patients undergoing surgical interventions for empyema at a major tertiary medical centre in Germany from 2017 to 2020 were analysed. The aim was to identify perioperative risk factors which significantly impact treatment outcomes but are currently not included in the RAPID score. 245 patients with pleural empyema surgically treated at the Department of General, Visceral and Thoracic Surgery at the University Medical Centre, Hamburg, Germany (admitted from January 2017 to April 2020) were retrospectively analysed. All patients which received either minimally invasive or open thoracic surgery were included. Epidemiological as well as perioperative data was analysed to identify risk factors which impact long-term overall outcomes. 90-day mortality rate was the primary endpoint. The mean age was 59.4 years with a bimodal distribution. There was a male predominance across the cohort (71.4% compared to 28.6%), with no significant differences across ages below or above 60 years. 53 (21.6%) patients died within the first 90 days. Diabetes type 1 and 2, renal replacement therapy, immunosuppression, postoperative bleeding, intraoperative transfusion as well as microbiologically confirmed bacterial invasion of the pleura all led to higher mortality rates. Higher RAPID scores accurately predicted higher 90-day mortality rates. Modifying the RAPID score by adding the comorbidities diabetes and renal replacement therapy significantly increased the predictive value of the score. We demonstrated various perioperative and patient related risk-factors not included in the RAPID score which negatively impact postoperative outcome in patients receiving surgical treatment for pleural empyema. These should be taken into consideration when deciding on the best course of treatment. If confirmed in a prospective study including non-surgical patients with a significantly larger cohort, it may be worth considering expanding the RAPID score to include these.

Electron irradiation of multilayer [Formula: see text] field effect transistors.

Palladium diselenide ([Formula: see text]) is a recently isolated layered material that has attracted a lot of interest for its pentagonal structure, air stability and electrical properties that are largely tunable by the number of layers. In this work, multilayer [Formula: see text] is used as the channel of back-gate field-effect transistors, which are studied under repeated electron irradiations. Source-drain [Formula: see text] electrodes enable contacts with resistance below [Formula: see text]. The transistors exhibit a prevailing n-type conduction in high vacuum, which reversibly turns into ambipolar electric transport at atmospheric pressure. Irradiation by [Formula: see text] electrons suppresses the channel conductance and promptly transforms the device from n-type to p-type. An electron fluence as low as [Formula: see text] dramatically changes the transistor behavior, demonstrating a high sensitivity of [Formula: see text] to electron irradiation. The sensitivity is lost after a few exposures, with a saturation condition being reached for fluence higher than [Formula: see text]. The damage induced by high electron fluence is irreversible as the device persists in the radiation-modified state for several hours, if kept in vacuum and at room temperature. With the support of numerical simulation, we explain such a behavior by electron-induced Se atom vacancy formation and charge trapping in slow trap states at the [Formula: see text] interface.

Fractionalized Fermionic Quantum Criticality in Spin-Orbital Mott Insulators.

We study transitions between topological phases featuring emergent fractionalized excitations in two-dimensional models for Mott insulators with spin and orbital degrees of freedom. The models realize fermionic quantum critical points in fractionalized Gross-Neveu* universality classes in (2+1) dimensions. They are characterized by the same set of critical exponents as their ordinary Gross-Neveu counterparts, but feature a different energy spectrum, reflecting the nontrivial topology of the adjacent phases. We exemplify this in a square-lattice model, for which an exact mapping to a t-V model of spinless fermions allows us to make use of large-scale numerical results, as well as in a honeycomb-lattice model, for which we employ ε-expansion and large-N methods to estimate the critical behavior. Our results are potentially relevant for Mott insulators with d^{1} electronic configurations and strong spin-orbit coupling, or for twisted bilayer structures of Kitaev materials.

In situ observation of lubricant film formation in THR considering real conformity: The effect of diameter, clearance and material.

The aim of the present study is to provide an analysis of protein film formation in hip joint replacements considering real conformity based on in situ observation of the contact zone. The main attention is focused on the effect of implant nominal diameter, diametric clearance and material. For this purpose, a pendulum hip joint simulator equipped with electromagnetic motors enabling to apply continuous swinging flexion-extension motion was employed. The experimental configuration consists of femoral component (CoCrMo, BIOLOX®forte, BIOLOX®delta) and acetabular cup from optical glass fabricated according to the dimensions of real cups. Two nominal diameters were studied, 28 and 36mm, respectively, while different diametric clearances were considered. Initially, a static test focused on the protein adsorption onto rubbing surfaces was performed with 36mm implants. It was found that the development of adsorbed layer is much more stable in the case of metal head, indicating that the adsorption forces are stronger compared to ceramic. A consequential swinging test revealed that the fundamental parameter influencing the protein film formation is diametric clearance. Independently of implant diameter, film was much thicker when a smaller clearance was considered. An increase of implant size from 28mm to 36mm did not cause a substantial difference in film formation; however, the total film thickness was higher for smaller implant. In terms of material, metal heads formed a thicker film, while this fact can be, among others, also attributed to clearance, which is more than two times higher in the case of ceramic implant.

New Limits on Extragalactic Magnetic Fields from Rotation Measures.

We take advantage of the wealth of rotation measures data contained in the NRAO VLA Sky Survey catalog to derive new, statistically robust, upper limits on the strength of extragalactic magnetic fields. We simulate the extragalactic magnetic field contribution to the rotation measures for a given field strength and correlation length, by assuming that the electron density follows the distribution of Lyman-α clouds. Based on the observation that rotation measures from distant radio sources do not exhibit any trend with redshift, while the extragalactic contribution instead grows with distance, we constrain fields with Jeans' length coherence length to be below 1.7 nG at the 2σ level, and fields coherent across the entire observable Universe below 0.65 nG. These limits do not depend on the particular origin of these cosmological fields.

Short- and long-term efficacy of intragastric air-filled balloon (Heliosphere® BAG) among obese patients.

BACKGROUND: Obesity is an increasing health problem worldwide. The intragastric balloon as a temporary endoscopic treatment of obesity can play an important role among the aforementioned group of obese individuals. It can also be used as a preoperative test before subjecting patients to restrictive bariatric surgery. Furthermore, the intragastric device may be applied to patients affected by severe obesity as a "bridge treatment" before they undergo major surgery in order to reduce chances of operation-related risks. To date, there are insufficient data in the literature on the long-term results of the intragastric balloon. METHODS: Our study includes an analysis of our experience with Heliosphere® BAG from 2006 through to 2010, concerning early weight loss and weight loss maintenance over at least 18 months since the device's removal. The 32 patients who completed the 6-month treatment had recorded a mean weight loss of 12.66 kg and a mean overweight loss of 24.37 % (SD, 12.74). RESULTS: A total of 16 patients are subjected to an 18-month follow-up. Their pretreatment and long-term body mass index (BMI) were calculated: 6 months later, when devices were removed, they showed a mean weight of 99.75 kg (SD, 17.90; p < 0.001) and a mean weight loss of 13.62 kg and 26.14 % (SD, 12.79). 18 months after removing Heliosphere® BAG, the 16 patients' mean BMI was 37.28 kg/m² (SD, 5.41; p = 0.004), with a mean weight of 103.56 kg (SD 17.25; p = 0.0125), and a mean weight loss of 9.8 kg or 18.2 % (SD, 12.07). CONCLUSIONS: Heliosphere® BAG enables modest short-term weight loss with little side effects, although mid/long-term follow-up may entail partial weight gain. We believe it can be considered a useful bridge treatment in bariatric surgery in order to reduce chances of preoperative risks.

Genetically engineered T cells expressing a HER2-specific chimeric receptor mediate antigen-specific tumor regression.

In this report, we developed a chimeric receptor (N29gamma chR) involving the single chain Fv (scFv) derived from N29 monoclonal antibody (mAb) specific for p185HER2 and characterized the therapeutic efficacy of primary T cells engineered to express N29gamma chR in two histologically distinct murine tumor models. Murine breast (MT901) and fibrosarcoma (MCA207) cancer cell lines were engineered to express human HER2 as targets. Administration of N29gamma chR-expressing T cells eliminated 3-day pulmonary micrometastases of MT901/HER2 and MCA207/HER2 but not parental tumor cells. A 5 to 8-fold increased dose of N29gamma T cells was required to mediate regression of advanced 8-day macrometastases. Exogenous administration of interleukin-2 (IL-2) after N29gamma T-cell transfer was dispensable for treatment of 3-day micrometastases, but was required for mediating regression of well-established 8-day macrometastases. Moreover, fractionated CD8 T cells expressing N29gamma chR suppressed HER2-positive tumor cell growth after adoptive transfer independent of CD4(+) cells. These data indicate that genetically modified T cells expressing a HER2-targeting chimeric receptor can mediate antigen-specific regression of preestablished metastatic cancers in a cell dose-dependent fashion. Systemic administration of IL-2 augments the therapeutic efficacy of these genetically engineered T cells in advanced diseases. These results are relevant to the implication of genetically redirected T cells in clinical cancer immunotherapy.

Gravitational particle production in braneworld cosmology.

Gravitational particle production in a time variable metric of an expanding universe is efficient only when the Hubble parameter H is not too small in comparison with the particle mass. In standard cosmology, the huge value of the Planck mass M{Pl} makes the mechanism phenomenologically irrelevant. On the other hand, in braneworld cosmology, the expansion rate of the early Universe can be much faster, and many weakly interacting particles can be abundantly created. Cosmological implications are discussed.

Fate and function of anti-CD3/CD28-activated T cells following adoptive transfer: IL-2 promotes development of anti-tumor memory T cells in vivo.

BACKGROUND: Adoptive immunotherapy with T cells activated through CD3 alone requires exogenous IL-2 for T-cell function and survival after transfer, but the in vivo cytokine requirement of T cells activated through CD3 and CD28 is unknown. We hypothesized that CD3/CD28-activated T cells, unlike those activated through CD3 alone, might develop into long-lived memory T cells, either with or without systemic IL-2. METHODS: We used MHC class I-restricted TCR transgenic T cells from the OT-1 mouse, specific for the surrogate tumor Ag ovalbumin (OVA), to assess the trafficking kinetics, antigenic responsiveness and anti-tumor efficacy of dual-activated T cells in vivo as a function of IL-2 administration. At days 7, 14, and 28 after transfer, lymph node cells and splenocytes were examined for donor cell persistence and antigenic responsiveness by FACS and ELISA, respectively. RESULTS: In IL-2-treated mice, donor CD8+ T cells persisted and developed a memory phenotype, based on CD44 and Ly6c expression at day 28, while mice given no IL-2 had fewer donor cells at all time points. OVA-specific release of IFN-gamma was higher from lymphocytes of IL-2-treated mice compared with no-IL-2 mice (P<0.02 at all time points). In mice challenged with an OVA-bearing subline of the AML leukemia model C1498, IL-2 did not confer added protection from tumor challenge at 1 or 2 weeks after adoptive transfer, but gave improved survival at 4 weeks post-transfer. DISCUSSION: We conclude that exogenous IL-2 is not required for anti-tumor activity of CD3/CD28-activated CD8+ cells early after adoptive transfer, but promotes T-cell persistence that confers disease protection at more remote times.

Reconstruction of maxilla alveolus for application of dental implant in patients with cleft defect.

The prospective study of dental implant application into the reconstructed maxilla alveolus of cleft patients was started in 2001. Its aims are to specify precisely the indications, conditions and techniques, as well as the factors justifying the assumption that the results will be successful. Indication was based on an examination by a multidisciplinary therapeutic team (plastic surgeon, dental surgeon, orthodontist, and prosthetist), with the proviso that the patient should have a positive approach. Successful orthodontic treatment of intergnathic relation and shape of the dental arches served as the basis. It was followed by a reconstruction of the defective alveolus using autologous cancellous bone grafts, harvested from an iliac crest. Dental implants were inserted 12-15 weeks after the transplantation and subsequently a prosthetic component was applied with a time delay of at least 2 months. After the orthodontic preparation, reconstruction of the alveolus has so far been performed in 38 patients. Their age was at least 14 years, i.e. the age when growth of the orofacial region was finalised or already complete. The crucial tasks at this stage are to form a stable, three-dimensional voluminous alveolar crest, and to cover the grafts with a sufficient amount of quality soft tissue. We needed an average amount of 3.7 ccm of cancellous bone graft for the reconstruction. This amount can be harvested only from an enchondral bone. For soft tissue shell the mucoperiosteal shift of flap from cleft segment was used. In more serious cases contralateral or even bilateral shift was performed. The relief of tissue tension was performed by double cut-back. Using the approach described we attained a 84.2% success rate. Our results and experience derived within this project show that the success rate of this procedure depends on the continuous flow of the alveolar arch with a good intergnathic relation, with a length of defect between crowns of border teeth of at least 8 mm. The original osseous walls of the defect must definitely be of suitable height. On-lay augmentation does not work in these cases. A subsequent pitfall lies in resorption of transplanted bone, which may be reduced due to an early load by a dental implant. During the three months after the reconstruction a spongy osseous graft matures enough to ensure the primary stability of a fixture. We emphasise the necessity of close co-operation of the therapeutic team in such cases.

Plastia intraarticular versus intra y extraarticular combinada en el tratamiento de la laxitud anterior crónica de rodilla / Intra-articular versus combined intra and extra-articular plasty in the treatment of chronic anterior knee laxity

Se realizó un estudio retrospectivo de 59 pacientes operados de laxitud anterior crónica de rodilla, para comparar dos técnicas de reparación: plastia intraarticular con tendón rotuliano (grupo 1) y plastia combinada intra y extraarticular (grupo 2). Treinta pacientes formaban parte del grupo 1 y 29 del 2; con una edad media de 28,6 y de 28,9 años y un tiempo medio de seguimiento de 7,5 y 7,8 años, respectivamente. Se evaluó el nivel y la frecuencia de actividad deportiva, el estado funcional según la escala del Comité Internacional de Documentación de la Rodilla. Se valoraron, mediante radiografías, los cambios degenerativos y la diferencia de traslación anterior de la tibia respecto a la rodilla normal. En los dos grupos disminuyó el nivel y la frecuencia de actividad deportiva. La evaluación funcional final fue similar en ambos grupos, considerándose la rodilla normal o casi normal en el 83 por ciento de los casos. Un 86,6 por ciento de pacientes del grupo 1 y un 89,6 por ciento del grupo 2, presentaron una estabilidad anteroposterior clínica normal o casi normal y un 73,3 por ciento y un 48,3 por ciento, respectivamente, presentaron una diferencia de traslación anterior radiográfica igual o inferior a 3 mm respecto a la rodilla normal.La plastia intraarticular aislada proporciona resultados similares a la combinación de una plastia intra y extraarticular, por lo que no está justificada la asociación de plastias extraarticulares a la plastia intraarticular en el tratamiento de la laxitud crónica de rodilla (AU)

Influence of mean climate change on climate variability from a 155-year tropical Pacific coral record.

Today, the El Niño/Southern Oscillation (ENSO) system is the primary driver of interannual variability in global climate, but its long-term behaviour is poorly understood. Instrumental observations reveal a shift in 1976 towards warmer and wetter conditions in the tropical Pacific, with widespread climatic and ecological consequences. This shift, unique over the past century, has prompted debate over the influence of increasing atmospheric concentrations of greenhouse gases on ENSO variability. Here we present a 155-year ENSO reconstruction from a central tropical Pacific coral that provides new evidence for long-term changes in the regional mean climate and its variability. A gradual transition in the early twentieth century and the abrupt change in 1976, both towards warmer and wetter conditions, co-occur with changes in variability. In the mid-late nineteenth century, cooler and drier background conditions coincided with prominent decadal variability; in the early twentieth century, shorter-period (approximately 2.9 years) variability intensified. After 1920, variability weakens and becomes focused at interannual timescales; with the shift in 1976, variability with a period of about 4 years becomes prominent. Our results suggest that variability in the tropical Pacific is linked to the region's mean climate, and that changes in both have occurred during periods of natural as well as anthropogenic climate forcing.

The important role of residue F268 in ligand binding by LXRbeta.

Liver X receptors (LXRs) are nuclear receptors that regulate the metabolism of cholesterol and bile acids. Despite information on the specificity of their natural ligands, oxysterols, relatively little is known about the ligand binding site in LXRs. The helix 3 region in the ligand binding domain (LBD) of peroxisome proliferator-activated receptors (PPARs) has been implicated in ligand entry. Sequence alignment of LXRs, farnesoid X receptor (FXR), and PPARs identified the corresponding helix 3 region in the LXRbeta LBD. Residues F268 and T272, which are conserved in all the aligned sequences and only in LXRs and FXR, respectively, were replaced with alanine. The effects of these mutations on ligand binding and receptor activation were examined using an in vitro ligand binding assay and a cell based reporter assay, respectively. The LXRbeta mutant F268A did not bind ligand. In contrast, conversion of T272 to alanine has no effect on ligand binding. By transiently expressing a chimeric receptor containing Escherichia coli tetracycline repressor (TetR) and LXRbeta LBD and a reporter with a TetR binding site, we show that mutant F268A lost the ability to activate transcription of the reporter, whereas mutant T272A still has an activity similar to that of the wild-type LXRbeta. These data, consistent with the findings in the in vitro ligand binding assay and our 3D modeling, are the first study that identifies a residue critical for ligand binding in LXRbeta.

Comparison of thrice weekly vs daily human leucocyte interferon-alpha therapy for chronic hepatitis C. TVVH Study Group.

Standard treatment for chronic hepatitis C currently consists of 3-6 million units (MU) of interferon-alpha (IFN-alpha) given thrice weekly (t.i.w.) for 12 months, obtaining rates of sustained response (SR) that usually do not exceed 15-25%. Some recent reports have suggested that daily administration of IFN-alpha may be more efficacious. More than 7 years ago, when standard therapy for hepatitis C was usually given for 6 months, we conducted a randomized clinical trial comparing daily vs t.i.w. treatment. In this study, 149 patients with chronic hepatitis C were randomized to received 3 MU of IFN-alpha either t.i.w. for 6 months or daily for 3 months followed by t.i.w. for 3 months. All patients were treated with human leucocyte IFN-alpha and were followed-up for up to 72 months after inclusion. Overall, patients treated daily or t.i.w. had similar rates of virological response after 3 months of induction [24/49 (50%) vs 40/100 (40%)], at the end of therapy [15/49 (31%) vs 36/100 (36%)] and at the end of follow-up [6/49 (12%) vs 9/100 (9%)]. However, when patients infected with HCV types other than HCV-1 were studied, there was a trend favouring the daily schedule that was associated with a higher [5/20 (25%) vs 5/48 (10%)] rate of long-term SR. All patients with a virological response - hepatitis C virus (HCV) RNA negative in serum as determined using the polymerase chain reaction - at 6 months after therapy remained in biochemical and virological remission at long-term follow-up, while seven of eight subjects who had normal alanine aminotransferase (ALT) levels but were serum positive for HCV RNA at 6 months, relapsed later, indicating that serum HCV RNA is better than ALT at predicting long-term cure after IFN-alpha therapy in chronic hepatitis C.

Chemically enucleated mouse oocytes: ultrastructure and kinetics of histone H1 kinase activity.

The objective of the study was to characterize the ultrastructure changes and biochemical mechanisms underlying the expulsion of the entire chromosome complement in chemically enucleated mouse oocytes. The ultrastructural studies demonstrated that the morphology of cytoplasts produced by etoposide-cycloheximide treatment were indistinguishable from intact metaphase I and II oocytes. Moreover, polar bodies formed by chemical enucleation were in almost all cases completely separated from the parent cytoplast and differed from normal polar bodies only in their chromatin content morphology and because they contained a slightly higher number of cytoplasmic organelles. The mode of polar body formation, however, in normal and chemically enucleated oocytes differs substantially: spindle involvement is important for normal polar body extrusion but plays no part in the protracted expulsion of chromosomes during chemical enucleation. After etoposide-cycloheximide treatment, histone H1 kinase activity remains high for the ensuing 6-8 h before declining gradually to basal levels 14 h after treatment. The expulsion of the polar body occurred only after the slowly declining H1 kinase activity reached basal levels. The activity of this kinase rose sharply to reach maximal levels within 4 h when the enucleated oocytes were removed from the inhibitor-supplemented medium and placed in normal medium. The findings in this paper indicate that cytoplasts produced by chemical enucleation are morphologically normal, thus suggesting that these enucleated cells are suitable for cloning studies. Although effective in mouse oocytes, we postulate that certain modifications to the enucleation technology are necessary before a reliable non-invasive protocol for ungulate oocytes will be available.

Mouse oocyte maturation: the effect of modified nucleocytoplasmic ratio.

Fully grown mouse oocytes isolated from large antral follicles and cultured in vitro complete their maturation up to the second metaphase with extrusion of the first polar body (1PB) with a 40/50 proportion (80%). When their cytoplasmic volume is, however, reduced before the onset of culture, the frequency of oocytes completing maturation gradually decreases. In the half oocytes, 66% (33/50) extruded 1PB, while in third oocytes the proportion was 57% (28/49) and in quarter oocytes no polar bodies were extruded. The time course of germinal vesicle breakdown was also delayed in comparison to the decreased cytoplasmic volume. Moreover, the isolated germinal vesicles surrounded with a thin cytoplasmic rim only remained intact after a prolonged culture. The full competence of complete maturation can be restored by fusion of an additional cytoplast to the manipulated nucleate parts. We postulate that a critical nucleocytoplasmic volume ratio is absolutely necessary for normal maturation in mammalian oocytes.

A composite reference section for terminal proterozoic strata of southern Namibia.

Integrated sequence stratigraphic and chemostratigraphic data yield a framework for correlations of stratigraphic units in the terminal Proterozoic to Cambrian Witvlei and Nama Groups of Namibia. Coupled with precise U-Pb zircon age constraints, these correlations make it possible to construct a composite reference section for use in calibrating terminal Proterozoic chronostratigraphy. The Namibian reference section starts with two distinct glacial horizons and extends up to within 1 million years of the Proterozoic-Cambrian boundary. The two glacial horizons may represent each of two distinct Varanger-age glaciations better known from the North Atlantic region. From the higher of the two glacial horizons up, the composite stratigraphy preserves one of the thickest and most complete available records of carbon-isotope variability in post-Varanger terminal Proterozoic seawater. Four carbon-isotope chemostratigraphic intervals are recognized: (1) a postglacial negative delta 13C excursion (Npg interval); (2) a rising interval (Pr interval) of increasing positive delta 13C values; (3) a falling interval (Pf interval) characterized by decreasing positive delta 13C and culminating in near zero or negative values; and (4) an interval of moderately positive, relatively invariant delta 13C values (I interval) that extends up to the unconformity that contains the Proterozoic-Cambrian boundary. Each of these chemostratigraphic intervals can be recognized in widely separated correlative sections around the world. By comparing sediment accumulation rate in the radiometrically calibrated Namibian stratigraphy with sediment accumulation rates in correlative sections in Arctic Canada and Oman, a maximum age of 564 Ma is estimated for the end of the younger Varanger glaciation, 25 m.y. younger than previous estimates.

Efficacy of a second cycle of interferon therapy in patients with chronic hepatitis C.

BACKGROUND & AIMS: Approximately 75%-85% of patients with chronic hepatitis C virus (HCV) infection do not have a sustained response when treated with interferon (IFN). Limited information exists on the efficacy of retreatment with IFN alone in these patients. The aim of this study was to define the efficacy of IFN retreatment in chronic hepatitis C. METHODS: Ninety-two patients with chronic hepatitis C who had shown transient or no response to recombinant IFN-alpha were randomly retreated with different schedules of lymphoblastoid IFN-alpha and followed up for 12 months after therapy to define biochemical and virological response. RESULTS: None of 26 initial nonresponders obtained a sustained response with retreatment, independent of the schedule used. Thirteen of 66 patients (20%; 95% confidence interval [CI], 10.9-31.3) with transient response during the primary cycle developed a sustained biochemical and virological response when retreated, including 3 of 41 (7%; 95% CI, 1.5-9.9) of those receiving the same schedule and 10 of 25 (40%; 95% CI, 21.1-61.3; P < 0.004) of those retreated with a higher dosage and for a longer period. Shorter disease duration (P = 0.02), higher alanine aminotransferase (P = 0.002) and lower gamma-glutamyltransferase levels (P = 0.004), HCV genotype other than HCV-1 (P = 0.03), and a negative serum HCV-RNA test at the end of the primary cycle (P = 0.000) were associated with sustained response. CONCLUSIONS: Patients with chronic hepatitis C who have a relapse after a complete response to a 6-month IFN-alpha treatment should be retreated for 12 months. Nonresponders should not be retreated with IFN alone.