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Autologous hematopoietic stem cell transplantation (aHSCT) is a promising therapy for multiple sclerosis (MS), which has mainly been used in adults. The purpose of this study was to investigate efficacy and adverse events of aHSCT in the treatment of children with MS using data from the European Society for Blood and Marrow Transplantation registry. Twenty-one patients with a median follow-up time of 2.8 years could be identified. PFS at 3 years was 100%, 16 patients improved in expanded disability status scale score and only 2 patients experienced a clinical relapse. The procedure was generally well tolerated and only two instances of severe transplant-related toxicity were recorded. There was no treatment-related mortality, although one patient needed intensive care. aHSCT may be a therapeutic option for children with disease that does not respond to standard care.

•Incidence of conversion to SPMS decreased markedly in Sweden after 1995.•First generation disease modifying drugs were introduced in Sweden by 1995.•We observed consecutive untreated and treated cohorts, and a calendar year function.•Using population cohorts reduced indication bias, and inclusion bias was considered.•Introduction of disease-modifying drugs probably reduced conversion to SPMS.

Stable oxygen and hydrogen isotopic compositions (δ18O and δD) of rainwater collected between 2009 and 2011 CE from Hailakandi, southern Assam, north-eastern India have been measured to characterize the extreme rainfall phenomena, delineate moisture sources, determine amount effect and assess the prospect of local proxies for paleoclimate studies. The δ18O values range from +0.7 to −13.8‰ while δD varies between +12 and −98‰. During the pre-monsoon months (March to May), heavy rains and thunderstorms, called nor’westers (Kal Baisakhiin local parlance), occur in some years giving rainfall as much as the monsoons. Strong evaporation and localised convection due to elevated air and sea surface temperature in the region and over the adjacent Bay of Bengal seem to cause nor’wester activity. No amount effect is observed in rain. The d-excess values for nor’wester rains is very different from those of monsoon rain; very low d-excess values (up to −26‰) were observed in 2010 CE and attributed to vapour originated from re-evaporation of freshwater, contributed by the lowland water bodies and rivers. The meteoric water line for the nor’wester rains, unlike that for the monsoon season, is significantly different from the Global Meteoric Water Line (GMWL). During the monsoon, the rain becomes progressively more depleted in the heavier isotopes (D and 18O), with the lowest δ values occurring in Sep-Oct. Oxygen isotope-based paleoclimatic study in this region appears to be confounded by a strong dependence of the rainwater isotopic composition on the source of moisture, uneven distribution of rains during the monsoon and the pre-monsoon seasons and the absence of amount effect.

Mechanisms of bone invasion by squamous carcinomas of the head and neck have been investigated using fresh tumours and established tumour cell lines in an in vitro bone resorption assay with 45Ca-labelled mouse calvaria. Fresh tumours regularly resorb bone in vitro. Activity is consistently reduced by indomethacin. The tumours release E2 prostaglandins (PGE2) in amounts sufficient to account for approximately 50% of the bone resorption observed. Small amounts of non-prostaglandin (indomethacin-resistant) osteolytic factors are also produced. Control non-neoplastic tissues show a variable capacity to resorb bone in vitro; PGE2 levels in these tissues may be related to their content of inflammatory cells. Tumour cell lines also resorb bone in vitro but, for most lines, activity is not significantly blocked by indomethacin and PGE2 levels are generally insufficient to account for the osteolysis observed. Non-prostaglandin bone resorbing factors thus predominate. It is concluded that most squamous cancers of the head and neck are osteolytic in vitro and release a mixture of prostaglandin and non-prostaglandin factors which stimulate osteoclastic bone resorption. These factors are derived from both neoplastic and stromal elements, and are "tumour-associated" rather than "tumour-specific". in vitro bone resorption and prostaglandin release does not correlate with pathological features of the tumour or with post-operative survival.

An in vitro osteolysis assay with 45Ca-labelled mouse calvaria has been used to investigate mechanisms of direct bone invasion by squamous carcinomas of the head and neck. Short-term (3-day) organ cultures of 8 fresh squamous carcinomas showed varying degrees of in vitro bone-resorbing activity which was blocked by indomethacin, an inhibitor of prostaglandin synthesis. Supernatant media from 6 established cell lines also induced bone resorption in vitro and evoked an osteoclastic response in the cultured calvaria. Osteolysis by supernatant media was not blocked by indomethacin in all the tumour-cell lines, and the production of non-prostaglandin osteolysins by the indomethacin-resistant lines is postulated. The two principal findings that emerge are: (1) Stimulants for osteoclastic activity are derived from both squamous-carcinoma cells and from host cells in the tumour stroma. (2) These stimulants are diverse. Indomethacin-sensitive agents, presumed to be prostaglandins, are most convincingly demonstrated in the fresh tumours. Indomethacin-resistant agents, presumably not prostaglandins, are more characteristic of the carcinoma cell lines.

13. Don and Mandarin—Memoirs of an Economist.By Sir Donald MacDougall. ISBN 0 7195 4424 6. Murray, London, 1987. 264 pp. £14.95.