Search

Purpose of review Early access to rheumatology is imperative to achieve appropriate outcomes in rheumatologic diseases. But there seems to be a significant gap and disparity in the access to rheumatology care between urban and rural areas. This review was undertaken to analyze this issue. Recent findings A significant delay in diagnosis of rheumatic disorder has been correlated to the travel distance to rheumatologist. It is also clear that currently, a significant rheumatology workforce shortage exists and is projected to worsen significantly, thereby making this gap and disparity much bigger. Summary The scope of this gap and disparity in rheumatology care for rural patients remains incompletely defined and quantified. It is felt to be a significant issue and it is important to invest resources to obtain information about its scope. In addition, a number of solutions already exist which can be implemented using current network and infrastructure. These include relatively low-cost interventions such as patient navigator, remote rheumatology experts and if possible tele-rheumatology. These interventions can assist temporarily but a major improvement will require policy change at federal and state government level as well as involvement, buy-in, and incentivization of the providers and health networks providing rheumatology care.

Background England has experienced high rates of SARS-CoV-2 infection during the COVID-19 pandemic, affecting in particular minority ethnic groups and more deprived communities. A vaccination programme began in England in December 2020, with priority given to administering the first dose to the largest number of older individuals, healthcare and care home workers. Methods A cross-sectional community survey in England undertaken between 26 January and 8 February 2021 as the fifth round of the REal-time Assessment of Community Transmission-2 (REACT-2) programme. Participants completed questionnaires, including demographic details and clinical and COVID-19 vaccination histories, and self-administered a lateral flow immunoassay (LFIA) test to detect IgG against SARS-CoV-2 spike protein. There were sufficient numbers of participants to analyse antibody positivity after 21 days from vaccination with the PfizerBioNTech but not the AstraZeneca/Oxford vaccine which was introduced slightly later. Results The survey comprised 172,099 people, with valid IgG antibody results from 155,172. The overall prevalence of antibodies (weighted to be representative of the population of England and adjusted for test sensitivity and specificity) in England was 13.9% (95% CI 13.7, 14.1) overall, 37.9% (37.2, 38.7) in vaccinated and 9.8% (9.6, 10.0) in unvaccinated people. The prevalence of antibodies (weighted) in unvaccinated people was highest in London at 16.9% (16.3, 17.5), and higher in people of Black (22.4%, 20.8, 24.1) and Asian (20.0%, 19.0, 21.0) ethnicity compared to white (8.5%, 8.3, 8.7) people. The uptake of vaccination by age was highest in those aged 80 years or older (93.5%). Vaccine confidence was high with 92.0% (91.9, 92.1) of people saying that they had accepted or intended to accept the offer. Vaccine confidence varied by age and ethnicity, with lower confidence in young people and those of Black ethnicity. Particular concerns were identified around pregnancy, fertility and allergies. In 971 individuals who received two doses of the Pfizer-BioNTech vaccine, the proportion testing positive was high across all age groups. Following a single dose of PfizerBioNTech vaccine after 21 days or more, 84.1% (82.2, 85.9) of people under 60 years tested positive (unadjusted) with a decreasing trend with increasing age, but high responses to a single dose in those with confirmed or suspected prior COVID at 90.1% (87.2, 92.4) across all age groups. Conclusions There is uneven distribution of SARS-CoV-2 antibodies in the population with a higher burden in key workers and some minority ethnic groups, similar to the pattern in the first wave. Confidence in the vaccine programme is high overall although it was lower in some of the higher prevalence groups which suggests the need for improved communication about specific perceived risks. Two doses of Pfizer-BioNTech vaccine, or a single dose following previous infection, confers high levels of antibody positivity across all ages. Further work is needed to understand the relationship between antibody positivity, clinical outcomes such as hospitalisation, and transmission.

IMPORTANCE: Patients with hypertrophic cardiomyopathy (HCM) are prone to body weight increase and obesity. Whether this predisposes these individuals to long-term adverse outcomes is still unresolved. OBJECTIVE: To describe the association of body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) with long-term outcomes in patients with HCM in terms of overall disease progression, heart failure symptoms, and arrhythmias. DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, retrospective data were analyzed from the ongoing prospective Sarcomeric Human Cardiomyopathy Registry, an international database created by 8 high-volume HCM centers that includes more than 6000 patients who have been observed longitudinally for decades. Records from database inception up to the first quarter of 2018 were analyzed. Patients were divided into 3 groups according to BMI class (normal weight group, 30). Patients with 1 or more follow-up visits were included in the analysis. Data were analyzed from April to October 2018. EXPOSURES: Association of baseline BMI with outcome was assessed. MAIN OUTCOME AND MEASURES: Outcome was measured against overall and cardiovascular mortality, a heart failure outcome (ejection fraction less than 35%, New York Heart Association class III/IV symptoms, cardiac transplant, or assist device implantation), a ventricular arrhythmic outcome (sudden cardiac death, resuscitated cardiac arrest, or appropriate implantable cardioverter-defibrillator therapy), and an overall composite outcome (first occurrence of any component of the ventricular arrhythmic or heart failure composite end point, all-cause mortality, atrial fibrillation, or stroke). RESULTS: Of the 3282 included patients, 2019 (61.5%) were male, and the mean (SD) age at diagnosis was 47 (15) years. These patients were observed for a median (interquartile range) of 6.8 (3.3-13.3) years. There were 962 patients in the normal weight group (29.3%), 1280 patients in the preobesity group (39.0%), and 1040 patients in the obesity group (31.7%). Patients with obesity were more symptomatic (New York Heart Association class of III/IV: normal weight, 87 [9.0%]; preobesity, 138 [10.8%]; obesity, 215 [20.7%]; P

Immunotherapy with immune checkpoint inhibitors (ICIs) has become a well-established modality to treat a number of different malignancies, especially in cases with advanced stages and/or recurrent diseases. These agents have been associated with development of a variety of autoimmune disorders as immune-related adverse events (IRAEs or irAEs). This review focuses on development of vasculitis with use of ICI. Available information on vasculitis associated with immune checkpoint inhibition is limited primarily to case reports at this time. Most immune-related adverse events will not present as vasculitis, and it is an uncommon manifestation and/or is under-reported. There are no current well-established guidelines for treating vasculitis associated with ICIs; initial management would usually start with consideration of discontinuing the ICI and administering corticosteroids. Collaboration between treating oncologists and rheumatologists is necessary for a combined approach to management. While arthralgias, myalgias, and inflammatory arthritis frequently occur as irAEs, vasculitis is an uncommon presentation. Vasculitis has been reported with all of the available ICI agents, and there seems to be no clear difference in the risk based on small numbers. Large vessel vasculitis and vasculitis of the nervous system were the most commonly reported types of vasculitis but cases of vasculitis involving medium and small vessels have also been reported. It is challenging to know if the underlying disease or ICIs are the main culprit in development of vasculitis and requires a collaborative relationship between the treating oncologist and rheumatologist. Except in very mild cases, development of vasculitis during ICI therapy requires temporary or permanent discontinuation of ICI.

We conducted ethnographic research in collaboration with a large, research‐intensive London breast cancer service in 2013–2014 so as to understand the practices and potential effects of stratified medicine. Stratified medicine is often seen as a synonym for both personalised and precision medicine but these three terms, we found, also related to distinct facets of treatment and care. Personalised medicine is the term adopted for the developing 2016 NHS England Strategy, in which breast cancer care is considered a prime example of improved biological precision and better patient outcomes. We asked how this biologically stratified medicine affected wider relations of care and treatment. We interviewed formally 33 patients and 23 of their carers, including healthcare workers; attended meetings associated with service improvements, medical decision‐making, public engagement, and scientific developments as well as following patients through waiting rooms, clinical consultations and other settings. We found that the translation of new protocols based on biological research introduced further complications into an already‐complex patient pathway. Combinations of new and historic forms of stratification had an impact on almost all patients, carers and staff, resulting in care that often felt less rather than more personal.

Apical hypertrophic cardiomyopathy (aHCM) is uncommon and apical myocardial infarction (MI) with normal coronary arteries is seen in 10% of these patients. We present an unusual case of aHCM with apical MI complicated by myopericarditis and large left ventricular (LV) thrombus in the setting of

Samples of amorphous MgSiO_3 annealed at temperature steps leading up to their crystallisation temperature show a rise in photoluminescence activity, peaking at ~450C. The photoluminescence band has a main peak at 595nm and a weaker peak at 624nm. We present laboratory data to show that the maximum in photoluminescence activity is related to substantial structural reordering that occurs within a relatively narrow temperature range. We attribute the origin of the photoluminescence to non-bridging oxygen hole centre defects, which form around ordered nano-sized domain structures as a result of the breakup of tetrahedral connectivity in the disordered inter-domain network, aided by the loss of bonded OH. These defects are removed as crystallisation progresses, resulting in the decrease and eventual loss of photoluminescence. Thermally processed hydrogenated amorphous silicate grains could therefore represent a potential carrier of extended red emission., Comment: 12 pages, 12 figs. Accepted for publication in MNRAS

A novel auto-stereoscopic 3D display system that forms dynamic exit pupils with the aid of a head-tracker is described Different views are displayed using time-multiplexing. Visible lasers, beam combiner, shaping and scanning optics and exit pupil control optics are discussed. It is estimated that 100 fL display brightness is achievable with about 3W per color of R, G and, B lasers.

Using a new device which contains an array of microlenses whose focal lengths can be electrically varied, we have been able to control the input from one microlens to a single mode fibre using an applied voltage. For such a microlens array many closely-spaced focal spots can be generated in parallel, and electrically switched to address, potentially, an array of receiver fibres. We show how the particular switching characteristics of the device, whereby the lenses switch from diverging to converging, serves in turn to disperse light and to focus it into the fibre.

Las observaciones aquí expuestas han sido total o parcialmente revisadas por muchos colegas, cuyas valiosas sugerencias han ayudado considerablemente a enfocar y mejorar las ideas iniciales, sin que, sin embargo, sean copartícipes de cualquier error de apreciación de los autores. Entre estos colegas queremos destacar a George Walker, Robin Holcomb, Bruce Nelson, Uri ten Brink, Tim Minshull, Tony Watts y Hubert Staudigel. Para todos ellos nuestro agradecimiento más sincero. Hans Schmincke realizó observaciones críticas muy acertadas en la presentación de estas ideas en la XXI Asamblea General de la International Union of Geodesy and Geophysics, celebrada en julio de 1995 en Boulder, CO, USA, que han contribuido a la clarificación de algunos aspectos fundamentales, lo que le agradecemos sinceramente., Las Islas Canarias son un grupo de islas volcánicas situadas sobre una placa oceánica en lento movimiento, cerca de un margen continental pasivo. Los orígenes del archipiélago suscitan la controversia: un punto caliente del manto, una zona de deformación litosférica, una región de fallas en bloques por compresión o una fractura que se propaga hacia el oeste desde el vecino Atlas han sido citados por diferentes autores como el origen último del archipiélago. Sin embargo, una comparación del Archipiélago Canario con el prototípico grupo de islas relacionado con un punto caliente, el Archipiélago de Hawaii, revela que las diferencias entre ambos no son tan grandes como se había supuesto anteriormente en base a datos más antiguos. La actividad eruptiva del Cuaternario en las Islas Canarias está concentrada en el extremo occidental del archipiélago, cerca del actual emplazamiento del punto caliente de referencia. Los edificios insulares en ambos archipiélagos se caracterizan por un crecimiento inicial rápido (las etapas de actividad en escudo ("shield stage"), seguidas por un período de reposo y profunda erosión ("gap" erosivo) que, a su vez, es seguido de una etapa de actividad "post-erosiva". Esta última etapa de actividad es más intensa en las Islas Canarias que en las Hawaii, tal vez debido a la velocidad mucho menor de la placa, lo que significa que las islas permanecen más tiempo cerca de la anomalía subyacente del manto. La geoquímica de las rocas en Canarias apoya con fuerza este modelo, que las relaciona con la fusión de materiales variados del manto enriquecidos más que con materiales normales del manto superior. La subsidencia de las islas en la etapa post-escudo es mucho menos significativa en las Islas Canarias que en las de Hawaii. Esto puede deberse a varios factores: una mayor resistencia de la litosfera oceánica subyacente, mucho más antigua y de mayor potencia en las Canarias que en Hawaii; la proximidad prolongada de las islas a esta pluma y la consiguiente sustentación dinámica; un crecimiento inicial más lento que lleva a un acercamiento más pausado de las islas al equilibrio dinámico antes de finalizar la etapa de construcción en escudo. Una comparación de la estructura y evolución estructural de las islas Canarias con las de otras islas oceánicas -Hawaii, Réunion, Fogo, etc.- revela muchas semejanzas, tales como la formación de zonas de triple rift (tipo "estrella Mercedes") y la ocurrencia de grandes colapsos laterales en los flancos de estas zonas de rift. La aparente ausencia de estas estructuras en las islas en etapa post-erosiva puede en parte ser una consecuencia de su mayor edad y del profundo desmantelamiento que ha eliminado la mayor parte de la evidencia de su arquitectura volcánica inicial. Concluimos que las numerosas semejanzas entre las Islas Canarias y aquellos grupos de islas cuyos orígenes en un punto caliente son indiscutibles parecen indicar que las islas Canarias se han formado en un proceso de similares características. Las “peculiaridades" geológicas de las Canarias con respecto a las demás alineaciones de punto caliente podrían deberse fundamentalmente a la menor actividad en Canarias del punto caliente y a la ausencia de subsidencia. Estas características geológicas generales ayudan a comprender mejor la distribución en el tiempo y el espacio de la actividad eruptiva en Canarias y, consecuentemente, del riesgo volcánico actual en las islas., Organismo Autónomo: Consejo Insular de Museos y Centros (OACIMC). Cabildo de Tenerife

15th May 1997

The 1677 volcanic eruption, located close to the town of Fuencaliente at the south end of La Palma, has been associated with the large voleanic cone of San Antonio, an emission centre showing relatively high energy phreatomagmatic phases. However, detailed geological mapping and a reinterpretation of available eye-witness accounts clearly prove the San Antonio emission centre to be a preexisting volcano related to an eruption that occurred several thousands years earlier. The 1677 eruption, or Volcán de Fuencaliente is a low magnitude eruption composed of a small strombolian vent and a cluster of aligned spatter vents. About 75-125 x 106 m3 of lavas from these spatter vents covered an area of 4.5 x 106 m2 and formed a wide coastal platform with 1.6 x 106 m2 of new land gained from the sea. This modest magnitude eruption is in better accord with the negligible damage caused to the arca reported in the contemporary accounts. This revision of the 1677 eruption and its magnitude is relevant for the precise reconstruction of the recent volcanism of La Palma and the correct definition of volcanic hazards in the island., La erupción de 1677, localizada cerca de la población de Fuencaliente en el S de la isla de La Palma ha sido asociada hasta ahora con el cono volcánico denominado San Antonio. Este centro de emisión presenta fases eruptivas de energía relativamente elevada. El estudio geológico de detalle de esta erupción y la reinterpretación de los relatos de la época indican que el volcán San Antonio es, en realidad, un aparato volcánico preexistente, relacionado con algún episodio eruptivo de varios miles de años de antigüedad. La verdadera erupción de 1677 o Volcán de Fuencaliente, es de baja magnitud y está formada por pequeños centros eruptivos estrombolianos y conos alineados de escorias. El volumen de lavas emitidas es de unos 75-125 x 106 m3 y cubre una extensión de aproximadamente 4,5 x 106 m2 de los cuales 1,6 x 106 m2 son terrenos ganados al mar. Esta erupción originó escasos daños en la zona, como se recoge en los relatos contemporáneos. La revisión de la erupción de 1677 es importante para el conocimiento del volcanismo reciente de La Palma y para la correcta definición del riesgo volcánico en la isla., This work was supported by the Spanish DGICYT Research Project PB92-0119.

Analysis of the evolution of the 1677 eruption of La Palma and the errors in the identification of the main vent, generally mistaken with the 3,000 years old San Antonio volcano.

A microlens immersed in a nematic liquid crystal cell has been constructed with avariable focal length which can be controlled by applying an analogue voltage to thenematic liquid crystal. The focal length is -910 ± 30 ? m with no electric field appliedand with an applied field the focal length can be varied from 380 ± 50 to 560 ± 20 ? malthough at present the lens performance is limited by aberrations. A microlens immersed in a nematic liquid crystal cell has been constructed with avariable focal length which can be controlled by applying an analogue voltage to thenematic liquid crystal. The focal length is -910 ± 30 ? m with no electric field appliedand with an applied field the focal length can be varied from 380 ± 50 to 560 ± 20 ? malthough at present the lens performance is limited by aberrations. 12 May 1995

The presence of the A*24020102L allele is implicated in one donor from the CBMD who serologically was typed as A2; B44, B55; Cwl, Cw7. The DRB4*01030102N allele was identified in one healthy donor and in one patient with MDS during routine HLA class II DNA typing. The DRB4*01030102N allele was identified in the patient's father, who had CML, and was associated with the HLA-A3-B7-Cw7-DRB1*0701-DQB1*0303 haplotype, which is common for European populations. In order to avoid mistyping, both techniques, serology and molecular biology must be used for HLA typing, especially for cases where just one antigen appeared to be present using serological methods.

The present study reports the successful shoot regeneration of preconditioned mature embryo and embryonic axis explants of chickpea cv. Gokce. Explants were preconditioned with 10 mgl benzylaminopurine (BA) for 7 days followed by culture on Murashige and Skoog (MS) medium containing 0.25, 0.50, 1.00 and 2.00 mg/l BA with or without 0.25 mg/l naphthalene acetic acid (NAA) supplemented with 4 mg/l activated charcoal and 1 mg/l polyvinylpyrrolidon (PVP). Shoot regeneration was recorded on all explants. Maximum number of (14.75) shoots per explants on mature embryo were recorded on MS medium containing 2.0 mg/l BA with 0.25 mg/l NAA. Whereas, 16.83 shoots per explants were recorded on MS medium containing 2.0 mg/l BA. Presence of NAA in the culture medium decreased the mean shoot length of both explants compared to medium devoid of 0.25 mg/l NAA. Regenerated shoots were rooted on MS medium containing 1.0 mg/l indole-butyric acid (IBA) after 4 weeks of culture. Rooted plantlets were transferred to pots for acclimatization under green house conditions.Key words: In vitro, chickpea, pulse treatment, shoot regeneration.

Purpose: Biochemotherapy can achieve high response rates in advanced melanoma, but the factors that influence regression and survival remain unknown. The present exploratory study tested the hypothesis that cytokine gene polymorphisms predict clinical outcome in stage IV melanoma patients treated with biochemotherapy.Experimental Design: Ninety patients with stage IV melanoma were treated with biochemotherapy, including cisplatin, vinblastine, and dacarbazine combined with interleukin (IL)-2 and IFN-α either with or without tamoxifen. Cytokine gene polymorphisms for IFN-γ (+874A→T) and IL-10 (−1082G→A) were assessed. X-ray repair cross-complementing gene 1 (XRCC1; Arg399Gln), xeroderma pigmentosum complementary group D (XPD; Lys751Gln), and excision repair cross-complementing gene 1 (ERCC1; codon 118) DNA repair polymorphisms were also determined.Results: IFN-γ (+874A→T) gene polymorphism was statistically significantly associated with response (P = 0.001), progression-free survival (P = 0.0012), and overall survival (P < 0.001), whereas the IL-10 polymorphism was marginally associated with response (P = 0.03) and overall survival (P = 0.065). Multivariate analysis revealed that IFN-γ (+874A→T) independently predicted overall survival (P = 0.003). The ERCC1 polymorphism was weakly associated with overall survival (P = 0.045). Combining polymorphisms for IFN-γ, IL-10, and ERCC1 stratified patients into four distinct groups with significantly different clinical outcome (P < 0.001), so that patients with more “favorable” polymorphisms had a better outcome.Conclusions: Cytokine gene polymorphisms predicted clinical outcome for advanced melanoma patients who received biochemotherapy. The combined effects of multiple genetic polymorphisms may provide more accurate prognostic information. Additional independent studies are needed to confirm these pilot findings.

Ipilimumab is a fully human, monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 to potentiate an antitumor T-cell response. This agent improved overall survival in a phase III trial in previously treated patients with advanced melanoma. Because the mechanism of action for ipilimumab is thought to be HLA independent, most trials enrolled patients without regard to HLA subtype. However, enrollment in the phase III trial was restricted to class-I HLA-A*0201-positive patients because two of the three arms contained an HLA-A*0201-restricted gp100 vaccine. HLA typing was also performed prospectively in several phase II trials and was available for 93.5% of patients. In this retrospective analysis, pooled efficacy and safety data are presented according to HLA-A*0201 status and dose from pretreated patients randomized to 0.3, 3, or 10 mg/kg ipilimumab in four phase II trials. Median overall survival (OS) was similar for the 187 HLA-A*0201-positive [9.3 months, 95% CI (confidence interval) 7.4-11.5] and 266 HLA-A*0201-negative patients [11.4 months, 95% CI 9.3-15.1] randomized to ipilimumab at all doses across the four phase II trials. These data are comparable to the OS for the 137 HLA-A*0201-positive patients randomized to ipilimumab in the phase III study [10.1 months, 95% CI 8.0-13.8]. Ipilimumab-induced adverse events and immune-related adverse events (skin, gastrointestinal, hepatic, other) also occurred at similar frequencies among patients in the phase II and III trials, regardless of HLA-A*0201 status. These findings support the hypothesis that ipilimumab-treated patients with advanced melanoma have similar outcomes regardless of their HLA-A*0201 status.

We evaluated the impact of weight loss (WL) using a Mediterranean diet and mild-to-moderate–intensity aerobic exercise program, on clinical status of obese, symptomatic patients with hypertrophic cardiomyopathy (HCM). Compared with nonresponders, responders showed a significant reduction of left atrial diameter, left atrial volume index (LAVI), E/Eʹaverage, pulmonary artery systolic pressure (PASP), and a significant increase in VO2max (%) and peak workload. Body mass index changes correlated with reduction in left atrial diameter, LAVI, E/Eʹaverage, PASP, and increase of VO2max (mL/Kg/min), VO2max (%), peak workload. Mediterranean diet and aerobic exercise is associated with clinical-hemodynamic improvement in obese symptomatic HCM patients.