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This study presents new field and petrological observations combined with geochemical data on a range of komatiitic to tholeiitic volcanic rocks from the ca. 3.48 Ga mid-lower Komati Formation type-section of the Barberton Greenstone Belt, South Africa. A range of mafic-ultramafic rocks is identified across a 1.44 km profile, leading to the proposition of a new preliminary volcanic architecture for the mid-lower Komati Formation type-section. Major, trace and rare earth element (REE) data in conjunction with Lu-Hf isotopic constraints indicate that the tholeiites, newly recognized highmagnesium basalts, basaltic komatiites and komatiites in the volcanic sequence have a primitive mantle signature with no geochemical affinity to Archaean or modern-day supra-subduction zone boninites. The whole rock initial εHf values of spinifex and massive komatiite flows in the lowermost part of the Komati type-section are negative, ranging between -1.9 and -3.1, whereas the second overlying spinifex and massive flow unit records positive initial εHf values between +0.5 and +4.7. A new geodynamic model involving crustal contamination of the mafic-ultramafic lavas is proposed for the Barberton mid-lower Komati Formation type-section, involving mantle plume-crust interaction. The new observations and data indicate that the komatiites erupted as a result of a mantle plume from a hot (>1 600oC) mid-Archaean mantle, in which the earliest volcanic flows were variably affected by crustal contamination during their ascent and eruption. The possibility of incorporation of lower crustal material and/or recycled crust residing in the mantle source region cannot be excluded. This indicates that modern-style plate tectonic processes, such as subduction, may not have been a requirement for the formation of the 3.48 Ga Barberton komatiite suite, with implications for the hydration state, geodynamic processes and secular thermal evolution of the Archaean mantle. [ABSTRACT FROM AUTHOR]

Background: A lack or dysfunction of the anchoring protein laminin‐332 in the basement membrane leads to the skin blistering disorder junctional epidermolysis bullosa (JEB). The mutation c.628G>A in the gene LAMB3 encoding the laminin β3‐chain is associated with generalized intermediate JEB; it may introduce an amino acid substitution (p.Glu210Lys) or disrupt splicing. Objective: This retrospective study aimed at determining the effects of aberrant splicing on the JEB phenotype. Methods: LAMB3 transcription was analysed in two siblings compound heterozygous for the LAMB3 mutations p.Glu210Lys and p.Arg635* with a diverging JEB phenotype from late childhood on. Laminin‐332 levels in skin sections and in cultured keratinocytes were investigated by immunofluorescence staining. Real‐time PCR was used to quantify LAMB3 expression in keratinocytes. RNA splice variants were identified by subcloning of a LAMB3 cDNA fraction and subsequent DNA sequencing. Structural models of laminin‐332 helped to assess the impact of certain mutations on laminin‐332 folding. Results: Both siblings showed diminished LAMB3 expression. Laminin‐332 was equally reduced in skin sections obtained during infancy but differed in keratinocytes isolated during adolescence. Although aberrant LAMB3 splicing with 26 variants was detected in both patients, splicing differed significantly: the full‐length LAMB3 transcript harbouring the p.Glu210Lys mutation was found more often in the patient affected less severely (14/108 vs. 5/106 clones; P = 0.03). Structural modelling predicted that several deletions in LAMB3, but not the point mutation p.Glu210Lys, have an effect on laminin‐332 folding and secretion. Conclusions: Differential LAMB3 mRNA splicing in the patients may explain the disparate JEB phenotype. By elucidating the regulation of laminin‐332 gene expression, these findings may contribute to the development of therapeutic strategies for JEB and might help to understand phenotype modification by splice‐site mutations in other hereditary diseases. Linked Commentary: D.F. Murrell et al. J Eur Acad Dermatol Venereol 2020; 34: 1879–1880. https://doi.org/10.1111/jdv.16859 [ABSTRACT FROM AUTHOR]

Transient response to nivolumab and relapse after infliximab in a patient with primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma Dear Editor, Primary cutaneous CD8 SP + sp aggressive epidermotropic T-cell lymphoma (CD8 SP + sp AECTCL) is a very rare subtype of cutaneous T-cell lymphoma. More recent studies evaluated the safety and efficacy of anti-PD-1 antibodies in patients with cutaneous T-cell lymphomas, including a phase Ib study for nivolumab that included 13 cases of mycosis fungoides and five cases of peripheral T-cell lymphoma. [Extracted from the article]

The Archean sub-seafloor has been proposed as an environment for the emergence of life, with septate clusters of titanite microtextures in pillow lava rims argued to be the earliest traces of microbial microboring. Here we use nanoscale secondary ion mass spectrometry (NanoSIMS) to test possible geochemical traces of life in ca. 3.45 Ga pillow lavas of the Barberton Greenstone Belt, South Africa. Sulfi de inclusions in the titanite microtextures record strongly negative sulfur isotope fractionations of δ34SVCDT --39.8‰ to --3.2‰ (VCDT--Vienna Canyon Diablo Troilite). These represent the largest range and most negative δ34S values so far reported from the Archean, and are consistent with an early biogenic origin for the sulfi des. Extensive in situ elemental mapping did not find any organic linings associated with the microtextures, despite the high spatial resolution and sensitivity of the NanoSIMS. The absence of organic linings thus excludes a key line of evidence previously used to support the biogenicity of the microtextures. In contrast, in situ sulfur isotope analysis of basalt-hosted sulfi des provides an alternative approach to investigating the existence and nature of an Archean subseafl oor biosphere. [ABSTRACT FROM AUTHOR]

Unlabelled: In Germany the number of invalidity pensions due to mental disorders is increasing. More than one third of these insurants do not take part in rehabilitation measures before their early retirement. Only 6 % return into their employment relationship., Hypotheses: 1. People with mental disorders still have severe health problems after their two-year temporary leave/retirement. 2. About one third of these insurants are generally interested in being reintegrated into their jobs. 3. Their motivation for reintegration depends on their age and their individual health status., Method: Data of all insurants (of DRV Braunschweig-Hannover) under 50 who drew a short-term benefit due to complete reduction in earning capacity in 2004 (n = 352) were collected with the help of an anonymous questionnaire (response rate = 54 %). This questionnaire compiled data on their general health status, their functional capacity and work ability, their motivation for returning to work as well as psychosocial aspects. At the same time, socio-demographic characteristics from the regional pension insurance database were analyzed., Results: Compared to patients treated in hospitals, those insurants who had been on a two-year temporary leave were psychologically strongly distressed. There was also a gender effect: Women in particular showed significant limitations in daily activities/routines, a higher level of anxiety and somatization. Less than 30 % of the pensioners were motivated for vocational rehabilitation in order to return to their jobs. The motivation was not dependant on the psychological load and the age but most probably on the somatization tendencies and the daily activities., Discussion: It seems that classic vocational rehabilitation for insurants who already receive a disability pension does not lead to a higher rate of reintegration into work. The relatively large number of insurants who want to return to their jobs implies the necessity of a special rehabilitation programme with concepts for reintegration: an individual case-management should help to continually counsel the patients and, by means of work-trial phases, prepare them for their return into their career.

Background and Aims: So far there is no agreement between clinical and radiological measurements and reference points for the quantification of pelvic organ descent in women. The aim of this study was to find out which of three reference lines on functional cine-magnetic resonance imaging (MRI) correlates best with the respective clinical diagnoses., Methods: We retrospectively evaluated the functional cine-MRI studies of 41 asymptomatic volunteers. Our golden standard was the results of the clinical examination using the International Continence Society (ICS)-score. On MRI, we measured the distance of the bladder-neck, distal edge of cervix/posterior fornix, and the most ventrocaudal point of the ventral rectal wall, respectively, to the pubococcygeal line (PCL), the horizontal tangent of the inferior rim of the pubic bone, and the line drawn through the long axis of the pubic bone. The results were correlated with the respective clinical findings using descriptive analysis alone., Results: The volunteers either showed a Stage 0 (16 cases), Stage I (12 cases), or a Stage II (13 cases) organ descent on clinical examination with 10 women (24.4%) having a pathological ICS-score in the anterior, 15 women (36.1%) in the superior, and 4 women (9.8%) in the posterior compartment. On functional MRI the best correlation with the clinical results was achieved using the PCL for the anterior compartment (22.0%), the PCL with an offset of +3 cm for the superior (36.6%), and the hymenal line (HL) for the posterior compartment (9.8%)., Conclusions: Organ descent on functional cine-MRI cannot be described using only one reference line. In order to optimize clinical exploitation of functional MRI of the pelvic floor a consensus regarding imaging protocols and evaluation criteria should be aimed for., (Copyright 2003 Wiley-Liss, Inc.)

Attention has been repeatedly drawn to the necessity to support patients after psychosomatic rehabilitation with their transfer of skills acquired during their stay at the interface between their inpatient treatment and their reintegration into everyday life. The authors' concept of the outpatient aftercare was already introduced in an earlier paper. This article presents the results of the one-year follow-up. A comparison with a control group revealed a further reduction of patients' depression. In contrast to the control group, the reduction in fear and discomfort already achieved during inpatient rehabilitation remained stable. At the same time the ability to cope with everyday life was expanded. Compared with the control group the participants of the aftercare could reduce the absence from work, days spent in hospital and visits to the doctor more than twice as much. Methodological problems of the design of the study are critically discussed.

Purpose: To compare relapse rates and toxicity associated with para-aortic (PA) strip or PA and ipsilateral iliac lymph node irradiation (dogleg [DL] field) (30 Gy/15 fractions/3 weeks) for stage I testicular seminoma., Patients and Methods: Between July 1989 and May 1993, 478 men with testicular seminoma stage I (T1 to T3; no ipsilateral inguinoscrotal operation before orchiectomy) were randomized (PA, 236 patients; DL, 242 patients)., Results: Median follow-up time is 4.5 years. Eighteen relapses, nine in each treatment group, have occurred 4 to 35 months after radiotherapy; among these, four were pelvic relapses, all occurring after PA radiotherapy. However, the 95% confidence interval (CI) for the difference in pelvic relapse rates excludes differences of more than 4%. The 3-year relapse-free survival was 96% (95% CI, 94% to 99%) after PA radiotherapy and 96.6% (95% CI, 94% to 99%) after DL (difference, 0.6%; 95% confidence limits, -3.4%, +4.6%). One patient (PA field) has died from seminoma. Survival at 3 years was 99.3% for PA and 100% for DL radiotherapy. Acute toxicity (nausea, vomiting, leukopenia) was less frequent and less pronounced in patients in the PA arm. Within the first 18 months of follow-up, the sperm counts were significantly higher after PA than after DL irradiation., Conclusion: In patients with testicular seminoma stage I (T1 to T3) and with undisturbed lymphatic drainage, adjuvant radiotherapy confined to the PA lymph nodes is associated with reduced hematologic, gastrointestinal, and gonadal toxicity, but with a higher risk of pelvic recurrence, compared with DL radiotherapy. The recurrence rate is low with either treatment. PA radiotherapy is recommended as standard treatment in these patients.

Against the background of rehabilitation as practised within the legal German framework of statutory and compulsory old age pension insurance--this rehabilitation scheme having developed continually, getting more and more differentiated for the last 40 years--we welcome the post-graduates of the specialised training curriculae in Public Health. The post-graduates are expected not only to acquire differentiated knowledge of the various spheres of activities of the different statutory social insurance and welfare bodies, but also to possess so to say a "sixth sense" regarding the "quality" of the individual spheres. Governed by the concepts of economy of means, triftiness and efficiency it is always imperative to ensure that the best possible care is offered to an individual in need and to plan further developments. The postgraduate must therefore be capable of becoming integrated within a team and to appreciate the expectations of members of other professions in order to eventually participate in creating feasible solutions within the framework of the hierarchically preferential demands inherent in the various spheres.

All 244 patients with carcinoma of the thoracic oesophagus registered at the Mount Vernon Centre for Cancer Treatment during the decade from 1 January 1980 to 31 December 1989 have been audited. We have made a detailed analysis of 110 (45%) with localized disease considered unsuitable for surgery, who completed treatment solely by radiotherapy. The median survival of this group of patients was 8.2 months (range 0.2-54 months). Dysphagia was improved by radiotherapy in 77.3% of cases, the median duration of relief was 24 weeks (range 0-208 weeks) and was maintained until death in 40%. Life table analysis showed that radical compared with less than radical regimens of radiotherapy gave significantly superior relief of dysphagia. This result is unlikely to be due to case selection.

Continuous, hyperfractionated, accelerated radiotherapy (CHART) has been used at the Mount Vernon Cancer Treatment Center since January 1985. Patients with head and neck tumors and those with locally advanced non-oat cell carcinoma of the bronchus have formed the large majority of the 263 patients treated. Early reactions in the mucosae of the mouth and pharynx have been pronounced, but all have healed, while those in the skin have been less severe than with conventional radiotherapy. An unexpected late morbidity was radiation myelitis in four patients, but in other tissues including the skin, mucosae, the connective tissues, and the salivary glands, late changes appear reduced compared to those after conventional radiotherapy. In 92 patients with squamous cell carcinoma of the major sites in the head and neck region, of whom 71 were in Stages T3 and T4, a complete regression at the primary site and nodes was achieved in 90%. This can be compared with 62% in similar patients previously treated with curative intent at Mount Vernon between 1980 and 1985; the difference was maintained in follow-up (p = 0.003). Of 76 assessable patients with non-oat cell carcinoma of the bronchus, a complete radiological response has been achieved in 40%, compared to 12% in a retrospective group; again the difference has been maintained in follow up (p = 0.0001). A 1-year survival of 60% can be compared to 40% in the retrospective group and a 2-year survival of 29% compared to 12% (p = 0.01). With a reduction of permitted dose to the spinal cord, CHART gives promise for improvement in tumor control and a reduction in late morbidity. These promising results have led to multi-center randomized controlled clinical trials in carcinoma at the head and neck and in non-oat cell carcinoma of the bronchus. In these studies, CHART is being compared with conventional fractionated radiotherapy.

All patients with head and neck cancer attending the Regional Centre for Radiotherapy and Oncology at Mount Vernon hospital during the 8-year period from 1 January 1980 to 31 December 1987 have been included in this review. The 545 patients presenting a new primary carcinoma without evidence for metastasis outside the locoregional area, who were treated primarily by radiotherapy are the subject of this present audit. The characteristics of the patients, of the tumours and of the treatment given have been related to outcome. Early tumours (T1 and T2 which were node-negative) showed a complete response (CR) rate of 94% whereas more advanced tumours (T1 and T2 with palpable lymph nodes) showed a CR of 59%. The probability of local tumour control at 5 years was 77% in those without nodes and 20% in those with nodes. For more advanced disease (T3 and T4 tumours), initial CR was 72% in node-negative disease and 32% when the nodes were positive. At 5 years, the probability of local tumour control fell to 37% and 0 respectively. CR, freedom from recurrence and survival were statistically significantly related to T stage, N stage and site of primary tumour. The results compare favourably with those reported by other institutions. The development of medical audit and its influence on treatment policy are considered.

This study investigated the use of radiotherapy for patients perceived to be unsuitable for curative therapy. Patients were grouped according to whether their cancer was considered curable or incurable and whether they received radical or palliative schedules of radiotherapy. The latter group was further evaluated to clarify current practice, to examine the problems in establishing guidelines for treatment and as a basis for prospective audit. Results confirmed that therapy guidelines within the unit were in line with national practice. Changes in standard therapy were proposed in view of resource limitations and recent results from other surveys. A second audit in 1989, together with a formal costing exercise, showed a reduction in the median number of fractions per course in both patient groups. This study suggests that palliative radiotherapy was used selectively for patients likely to receive significant benefit, and that consensus management was practised, and influenced, by informal internal audit. Results highlighted decision-making problems in the management of advanced non-metastasised cancer; confirmed doubts about the advisability of establishing rigid guidelines in palliative therapy; and clarified some of the difficulties in conducting meaningful cost-benefit analyses in this area.

The use of electron beam therapy with energies up to 10 MeV in the treatment of basal and squamous cell carcinomata of the skin is described. The results of treatment of 15 cases are presented with photographs of six cases. Excellent clinical and cosmetic results have been obtained. Electron therapy has been found to be simple and convenient, avoiding the necessity for the use of radium moulds in a number of cases and thus avoiding radiation exposure of staff.

Shortening of the overall duration of radiotherapy would reduce the possibility repopulation of tumor during treatment. Most clinical trials of such accelerated radiotherapy have incorporated a split course to improve normal tissue tolerance. Any interruption, however, even for the week-end, may allow repopulation to occur. A scheme of radiotherapy has been used during which treatment was given 3 times per day on each of 12 consecutive days without interruption for the week-end. In a pilot study a significant improvement in survival and local tumor control has been achieved in 48 patients with head and neck tumors when comparison was made with a previously treated group. A randomized controlled clinical trial is planned.