Reducing the impact of radioactivity on quantum circuits in a deep-underground facility.

As quantum coherence times of superconducting circuits have increased from nanoseconds to hundreds of microseconds, they are currently one of the leading platforms for quantum information processing. However, coherence needs to further improve by orders of magnitude to reduce the prohibitive hardware overhead of current error correction schemes. Reaching this goal hinges on reducing the density of broken Cooper pairs, so-called quasiparticles. Here, we show that environmental radioactivity is a significant source of nonequilibrium quasiparticles. Moreover, ionizing radiation introduces time-correlated quasiparticle bursts in resonators on the same chip, further complicating quantum error correction. Operating in a deep-underground lead-shielded cryostat decreases the quasiparticle burst rate by a factor thirty and reduces dissipation up to a factor four, showcasing the importance of radiation abatement in future solid-state quantum hardware.

Real-world effectiveness and safety of apremilast in psoriasis at 52 weeks: a retrospective, observational, multicentre study by the Spanish Psoriasis Group.

BACKGROUND: Little has been published on the real-world effectiveness and safety of apremilast in psoriasis. OBJECTIVES: To evaluate the effectiveness, safety and drug survival of apremilast at 52 weeks in patients with moderate to severe plaque psoriasis or palmoplantar psoriasis in routine clinical practice. METHODS: Retrospective, multicentre study of adult patients with moderate to severe plaque psoriasis or palmoplantar psoriasis treated with apremilast from March 2016 to March 2018. RESULTS: We studied 292 patients with plaque psoriasis and 85 patients with palmoplantar psoriasis. The mean (SD) Psoriasis Area and Severity Index (PASI) score was 10.7 (7.0) at baseline and 3.0 (4.2) at 52 weeks. After 12 months of treatment, 73.6% of patients had a PASI score of 3 or less. In terms of relative improvement by week 52, 49.7% of patients achieved PASI-75 (≥75% reduction in PASI score) and 26.5% achieved PASI-90. The mean physician global assessment score for palmoplantar psoriasis fell from 4.2 (5.2) at baseline to 1.3 (1.3) at week 52. Overall drug survival after 1 year of treatment with apremilast was 54.9 %. The main reasons for treatment discontinuation were loss of efficacy (23.9%) and adverse events (15.9%). Almost half of the patients in our series (47%) experienced at least one adverse event. The most common events were gastrointestinal problems. CONCLUSIONS: Apremilast may be a suitable alternative for the treatment of moderate to severe psoriasis and palmoplantar psoriasis. Although the drug has a good safety profile, adverse gastrointestinal effects are common.

Circuit quantum electrodynamics of granular aluminum resonators.

Granular aluminum (grAl) is a promising high kinetic inductance material for detectors, amplifiers, and qubits. Here we model the grAl structure, consisting of pure aluminum grains separated by thin aluminum oxide barriers, as a network of Josephson junctions, and we calculate the dispersion relation and nonlinearity (self-Kerr and cross-Kerr coefficients). To experimentally study the electrodynamics of grAl thin films, we measure microwave resonators with open-boundary conditions and test the theoretical predictions in two limits. For low frequencies, we use standard microwave reflection measurements in a low-loss environment. The measured low-frequency modes are in agreement with our dispersion relation model, and we observe self-Kerr coefficients within an order of magnitude from our calculation starting from the grAl microstructure. Using a high-frequency setup, we measure the plasma frequency of the film around 70 GHz, in agreement with the analytical prediction.

Italian Intersociety Recommendations on pain management in the emergency setting (SIAARTI, SIMEU, SIS 118, AISD, SIARED, SICUT, IRC).

BACKGRAUND: Pain is the primary reason for admission to the Emergency Department (ED). However, the management of pain in this setting is often inadequate because of opiophagia, fear of excessive sedation, and fear of compromising an adequate clinical assessment. METHODS: An intersociety consensus conference was held in 2010 on the assessment and treatment of pain in the emergency setting. This report is the Italian Intersociety recommendations on pain management in the emergency department setting. RESULTS: The list of level A recommendations includes: 1) use of IV acetaminophen for opioid sparing properties and reduction of opioid related adverse events; 2) ketamine-midazolam combination preferred over fentanyl-midazolam fentanyl-propofol in pediatric patients; 3) boluses of ketamine IV (particularly in the population under the age of 2 years and over the age of 13) can lead to impairment of the upper airways, including the onset of laryngospasm, requiring specific expertise and skills for administration; 4) the use of ketamine increases the potential risk of psychomotor agitation, which can happen in up to 30% of adult patients (this peculiar side effect can be significantly reduced by concomitant systemic use of benzodiazepines); 5) for shoulder dislocations and fractures of the upper limbs, the performance of brachial plexus block reduces the time spent in ED compared to sedation; 6) pain relief and the use of opioids in patients with acute abdominal pain do not increase the risk of error in the diagnostic and therapeutic pathway in adults; 7) in newborns, the administration of sucrose reduces behavioural responses to blood sampling from a heel puncture; 8) in newborns, breastfeeding or formula feeding during the procedure reduces the measures of distress; 9) in pediatric patients, non-pharmacological techniques such as distraction, hypnosis and cognitive-behavioural interventions reduce procedural pain caused by the use of needles; 10) in pediatric patients, preventive application of eutectic mixtures of prilocaine and lidocaine allows arterial and venous samples to be taken in optimum conditions; 11) in pediatric patients, the combination of hypnotics (midazolam) and N2O is effective for procedural pain, but may be accompanied by loss of consciousness. CONCLUSION: The diagnostic-therapeutic pathway of pain management in emergency should be implemented, through further interdisciplinary trials, in order to improve the EBM level of specific guidelines.

Acrometastasis en tejidos blandos de la mano: Una forma de manifestación infrecuente del cáncer de pulmón. Revisión de la literatura / Achrometastasis in the soft tissues of the hand: A rare presentation of lung carcinoma. Review of the literature

Se describe un caso reciente de acrometástasis en partes blandas de mano y se realiza la primera revisión bibliográfica de esta excepcional presentación de las acrometástasis. Se trata de un varón de 74 años, fumador de 20 cigarrillos por día desde los 18 años, que consultó por una lesión exofítica sangrante en cara dorsolateral del índice izquierdo. Se realizó biopsia y extirpación del 2º eje del dedo (rayo). La radiografía fue normal y la anatomía patológica confirmó una metástasis de carcinoma espinocelular diferenciado con indemnidad ósea. En el estudio clínico se descubrió un carcinoma pulmonar que luego se complicó con una fístula esofago-traqueal tratada mediante un stent. Falleció un mes después en su domicilio por una hematemesis, 12 meses posteriores a la primera consulta. La acrometástasis fue la primera manifestación de una neoplasia y se produjo en los tejidos blandos de la mano, una forma muy rara de presentación. Las metástasis en los huesos de las manos y pies son raras. La incidencia en mano es de 0,25-0,60 porciento entre los tumores que dan metástasis óseas. Las acrometástasis en tejidos blandos son aún más raras y se han comunicado muy pocos casos. El comportamiento biológico de las metástasis pulmonares en los huesos y su extrema rareza no han sido dilucidados. En general ocurren durante la diseminación terminal de las neoplasias e indican un mal pronóstico. El tiempo promedio de sobrevida es habitualmente menor de un año. Ocasionalmente pueden ser la forma de presentación de un blastoma. Los tumores más frecuentemente producen estas lesiones son los de pulmón, riñón, mama y colon. Los tumores no carcinomatosos son causa excepcional de estas lesiones. A pesar de su rareza, estas acrometástasis pueden ser importantes por dos motivos: primero, pueden ser la primera manifestación de una neoplasia oculta. segundo, su sintomatología puede ser confundida y se demora el diagnóstico. Pueden simular enfermedades inflamatorias o enfermedades subungueales benignas. La biopsia convencional asegura el diagnóstico. La amputación quirúrgica suele ser el mejor tratamiento paliativo y la radioterapia puede a veces ser efectiva

Acrometastasis en tejidos blandos de la mano: Una forma de manifestación infrecuente del cáncer de pulmón. Revisión de la literatura / Achrometastasis in the soft tissues of the hand: A rare presentation of lung carcinoma. Review of the literature

Se describe un caso reciente de acrometástasis en partes blandas de mano y se realiza la primera revisión bibliográfica de esta excepcional presentación de las acrometástasis. Se trata de un varón de 74 años, fumador de 20 cigarrillos por día desde los 18 años, que consultó por una lesión exofítica sangrante en cara dorsolateral del índice izquierdo. Se realizó biopsia y extirpación del 2º eje del dedo (rayo). La radiografía fue normal y la anatomía patológica confirmó una metástasis de carcinoma espinocelular diferenciado con indemnidad ósea. En el estudio clínico se descubrió un carcinoma pulmonar que luego se complicó con una fístula es

Randomized controlled trial of audio computer-assisted self-interviewing: utility and acceptability in longitudinal studies. HIVNET Vaccine Preparedness Study Protocol Team.

Recent studies have reported on the utility of audio computer-assisted self-interviewing (ACASI) in surveys of human immunodeficiency virus (HIV) risk behaviors that involve a single assessment. This paper reports the results of a test of ACASI within a longitudinal study of HIV risk behavior and infection. Study participants (gay men (n = 1,974) and injection drug users (n = 903)) were randomly assigned to either ACASI or interviewer-administered assessment at their second follow-up visit 12 months after baseline. Significantly more of the sexually active gay men assessed via ACASI reported having sexual partners who were HIV antibody positive (odds ratio = 1.36, 95% confidence interval: 1.08, 1.72), and a higher proportion reported unprotected receptive anal intercourse. Among injection drug users (IDUs), our hypothesis was partially supported. Significantly more IDUs assessed via ACASI reported using a needle after another person without cleaning it (odds ratio = 2.40, 95% confidence interval: 1.34, 4.30). ACASI-assessed IDUs reported similar rates of needle sharing and needle exchange use but a lower frequency of injection. Participants reported few problems using ACASI, and it was well accepted among members of both risk groups. Sixty percent of the participants felt that the ACASI elicited more honest responses than did interviewer-administered questionnaires. Together, these data are consistent with prior research findings and suggest that ACASI can enhance the quality of behavioral assessment and provide an acceptable method for collecting self-reports of HIV risk behavior in longitudinal studies and clinical trials of prevention interventions.

Cell-specific regulation of alpha1(III) and alpha2(V) collagen by TGF-beta1 in tubulointerstitial cell models.

BACKGROUND: TGF-beta1 modulates the cellular expression of extracellular matrix (ECM) in several renal cell systems in vitro and is considered a determinant of ECM accumulation in tubulointerstitial fibrosis. METHODS: We evaluated the effects of TGF-beta1 on collagen transcription, expression, and removal of the relevant collagens by rat tubuloepithelial cells (NRK 52E) and both rat and monkey interstitial fibroblasts (NRK 49F, CV1) in vitro. RESULTS: TGF-beta1 upregulated the expression of alpha1(III) collagen by fibroblasts (+300%) without affecting its removal. In parallel, a threefold increment of COL3A1 mRNA was found. Experiments of cell transfection employing CV1 fibroblasts as the unique suitable model, and chimaeric constructs of COL3A1 and COL5A2 promoters fused to the luciferase reporter gene, demonstrated a twofold stimulation of a large 1436 COL3A1 promoter construct and negligible effects on shorter fragments, suggesting the presence of a positive responsive element in a region of COL3A1 promoter between -1375 and -579. TGF-beta1 did not influence COL5A2 mRNA and the relative promoter activity in renal fibroblasts. With NRK 52E cell line, TGF-beta1 induced comparable increment of both alpha1(III) collagen expression (+300%) and COL3A1 mRNA (+300%) without affecting the COL3A1 promoter activity of any constructs. TGF-beta1 also upregulated the expression of alpha2(V) collagen chain (+500%) and COL5A2 mRNA (+500%) with a stimulatory effect (+100%) on a 1177 bp fragment of COL5A2 promoter. In this case a relevant inhibitory effect of TGF-beta1, on removal of alpha2(V) by supernatants of NRK 52E was also observed, indicating a double regulatory role of the cytokine on both transcription and removal of this component of ECM. CONCLUSION: Taken together these data indicate that TGF-beta1 is a potent stimulator of alpha1(III) collagen expression by renal fibroblast cell lines in vitro, the basic mechanism being stimulation of COL3A1 transcription. With renal epithelial cell lines, TGF-beta1 mainly upregulated the expression of type V collagen with the most relevant effect on stimulation of collagen transcription and inhibition of its removal. Tubular epithelial cells and renal fibroblasts should play distinct roles in renal fibrosis induced by TGF-beta1 in vivo.

Effects of benzopsoralen derivatives on HL60 and HeLa cells.

The effect of 4-hydroxymethyl-6,7,8,9-tetrahydro-2H-benzofuro-[3,2-g]-1-benzo piran-2-one (compound 1) and 4-hydroxymethyl-2H-benzofuro-[3,2g]-1-benzopiran-2-one (compound 2), two new benzopsoralen derivatives, was tested on HL60 and HeLa cell lines in the dark and by UVA irradiation; 8-methoxypsoralen was used as a reference compound. The action of the compounds was evaluated by means of the neutral red uptake assay, by means of ultrastructure, morphometry and interaction with human erythrocytes membrane. In both HL60 and HeLa cell lines benzopsoralen derivatives showed more antiproliferative activity after UVA irradiation, however less than 8-methoxypsoralen. Compound 1 was more effective than compound 2 both in the dark and after UVA irradiation. The ultrastructure showed a morphological rank damage caused by these compounds: compound 2 induced slight modifications in the cytoplasm organization, compound 1 induced some vacuolizations and 8-methoxypsoralen generated plenty of vacuoles and an empty space around the nucleus. Morphometrical data in HL60 cells turned out to be in accordance with the different action mechanisms existing between 8-methoxypsoralen and the two benzopsoralen derivatives; in HeLa cells we noted an increase in the nuclear area induced by all the three compounds. Only compound 1 caused the formation of echinocytes both in the dark and after UVA irradiation, suggesting the involvement of a mechanism not strictly related to DNA interaction and singlet oxygen production.

Growth, morphology, morphometry and keratin patterns of bovine corneal epithelial cells cultured in vitro.

In this study, the effects of different culture systems on bovine corneal epithelial cells were analysed in order to better understand the influence of bovine keratocytes on epithelial cells. Growth, morphological, morphometrical analyses of cells and keratin patterns were evaluated. The aim was to improve the culture technique in order to obtain a good in vitro proliferation of these cells for their employment in clinical and toxicological situations. The bovine corneal epithelial cells were cultured under different conditions: on keratocyte or 3T3-J2 fibroblast feeder layers, with media conditioned either by the two feeder layers or with a basal medium. The epithelial cells cultured on a keratocyte feeder layer as compared to those grown under the other conditions, proved to have a higher growth rate as well as to be smaller in the cytoplasmic and nuclear area; moreover, after 21 days of culture they expressed 64-kDa keratin, designed as a marker for corneal epithelial cell differentiation. To sum up, the keratocyte feeder layer is the most effective for stimulating the growth and differentiation of corneal epithelial cells, resembling the in vivo situation. It might also be successfully employed for clinical and toxicological purposes.

Morphological features and kinetics of primary cultures of BPH tissue supported by TV1 medium.

222 human prostatic biopsies were used to prepare cell cultures by means of a medium--colony formation permissive--containing fetal calf serum, called TV1. After 7, 14 and 21 days, the cultures were examined by optical and scanning electron microscopy. TV1 medium induces the formation and growth of two types of colonies, one mainly composed of epithelioid cells and distinguished by early growth; the second one made up exclusively of fibroblastoid cells which appear later in the culture. Epithelioid colonies, comprising three different cell types, appear to be arranged as a growth halo concentric to the bioptic fragment with a large central area, formed by a monolayer, and a pluristratified edge. Fibroblastoid cells weakly adhere to the substrate and form "satellite growth halos" separated from the primitive bioptic fragment. All the epithelioid cells were positive to cytokeratin LP34 Mab and negative to anti-smooth muscle-actin and anti-proline-4-hydroxylase antibodies. Fibroblastoid cells were only anti-proline-4-hydroxylase positive. The cell kinetics of epithelioid cells were also studied, revealing an extension of the S phase, in contrast to what happened with WAJC 404, and consequently a reduction of the percentage of cells entering mitosis. For this reason, the addition of fetal serum to the culture medium does not allow the use of prostate primary cultures for more than 14 days.

Primary cultures of human hypertrophic prostate tissue in WAJC 404 medium: a study of cell morphology and kinetics.

222 biopsy fragments of human hypertrophic prostate tissue were cultured in WAJC 404 serum-free medium for three weeks. Growth halos were examined after 7, 14 and 21 days of culture by optical and scanning electron microscopy. Colonies formed of two concentric areas showed in the inner halo elementary pseudo-lobular morphological units similar to the prostate structure. The cell morphological patterns of the halo turned out to be four in number. Every cell pattern was defined morphologically, morphometrically and phenotypically. Results indicate that all morphological differences must be attributed to the various phases of cell life, as all cell types were positive to cytokeratin. The nonconstant display of PSAP and PSA showed a moderate tendency to cell differentiation in WAJC 404 medium. Cell kinetics were also studied and revealed a decrease in proliferation after 14 days of culture. Primary cultures from biopsy fragments of human hypertrophic prostate tissue may be used as an experimental model up to the 14th day of culture.

Peripheral nerve repair using a poly(organo)phosphazene tubular prosthesis.

Nerve regeneration experiments were carried out using tubular nerve guides of poly[(ethylalanato)1.4(imidazolyl)0.6phosphazene] (PEIP). By means of in vivo tests, this polymer was found to be biodegradable and transformed into harmless products. The tubular nerve guides were prepared by deposition of the dissolved polymer on a glass capillary tube, followed by evaporation of the solvent (methylene dichloride). After transectioning, rat sciatic nerve stumps were immediately sutured into the ends of 10-mm-long polymer tubes. On removal of the prosthesis, after implantation for 45 d, a tissue cable was found bridging the nerve stumps in all cases. Histological analysis revealed that the tissue cable was essentially composed of a regenerated nerve fibre bundle. A parallel series of experiments was undertaken to compare the use of silicone tubes that are not biodegradable and are most frequently used for studies of nerve regeneration with tubulization techniques. The advantages of biodegradable PEIP tubular nerve guides used for peripheral nerve repair are discussed.

Cyclosporine enhances the synthesis of selected extracellular matrix proteins by renal cells "in culture". Different cell responses and phenotype characterization.

Glomerulosclerosis and interstitial fibrosis are 2 major side effects of protracted therapy with CsA in heart transplant patients and in nonrenal immunologic diseases. To investigate whether there is any cause-effect correlation between CsA and the synthesis of extracellular matrix in the kidney, we determined the amount and composition of collagens produced by various renal cells "in culture" upon exposure to increasing levels of CsA. The cellular models we used included primary cultures of both human and rat mesangial cells (hMC, rMC), human and rat renal fibroblasts (hFib, rFib), and human tubular epithelia as well as cell lines of rat renal fibroblasts (NRK49F) and of tubular epithelia (NRK52E). In the case of primary cell cultures, CsA induced a marked increment of total collagen synthesis. This was highest for renal fibroblasts (+330% hFib, +110% rFib), followed by rMC (+170%), hMC (+100%), and human tubular epithelia (+130%). At the highest dosage of CsA (5 ng/ml), this corresponded to a net increment in collagen III synthesis by both hMC and hFib (+150% and +300%), while collagen I and collagen IV were unaffected. On hMC, CsA also induced a maximal increase in a component with 70 kDa molecular mass, which was produced only in a negligible amount by these cells in standard conditions. This low molecular mass collagen was tentatively characterized by cyanogen-bromide digestion and fingerprint analysis as a novel molecule showing a peptide composition without comparable features for any reported collagen map. NRK49F and NRK52E cell lines were not affected by CsA. Taken together, these observations demonstrate that CsA is able to induce the synthesis of specific collagens, mainly of collagen III and of a 70-kDa component, by various renal cells in cultures. Since the same cells are the renal site of production of extracellular matrix in pathological conditions, we hypothesize that this effect is a relevant one in the pathogenesis of glomerulosclerosis/interstitial fibrosis during protracted therapies with CsA.

Fibroblast-keratinocyte co-cultures in vitro: growth, morphometry and nutrient exchange.

The interaction between fibroblasts and rat keratinocytes co-cultured in vitro was examined. The epidermal cells cultured with a basal medium or with a conditioning medium (derived from fibroblast cultures) presented a lower growth rate and significantly greater cellular dimensions than those cells grown in the presence of a feeder layer. Qualitative and quantitative differences in the keratin patterns of the cells grown in the three cultural conditions were found. Keratinocytes cultured with the feeder layer expressed seven keratin types (58, 57, 53, 52, 50, 48 and 45 kDa), those with conditioning medium, five types (58, 53, 52, 48 and 45 kDa) and those with basal medium, only one type (45 kDa). This data confirms the dependence of keratinocytes on fibroblasts. HPLC analysis of the culture media, suggested that a protein factor (MW approximately 65 kDa) was secreted by fibroblasts into the culture medium. This factor was added to the keratinocyte culture medium (conditioning medium), and, after a 48 hour culture, was apparently completely removed from the medium by the keratinocytes. Moreover, the keratinocytes cultured with the feeder layer and exposed to indomethacin, a cyclo-oxygenase inhibitor, showed a decrease in growth rate at drug concentrations of < or = 10 microM which did not induce a reduction in the viability of the fibroblasts and keratinocytes in separate cultures. This preliminary data suggests a relationship between fibroblast PGE2 secretion and keratinocyte growth.