A distance to the Large Magellanic Cloud that is precise to one per cent.

In the era of precision cosmology, it is essential to determine the Hubble constant empirically with an accuracy of one per cent or better1. At present, the uncertainty on this constant is dominated by the uncertainty in the calibration of the Cepheid period-luminosity relationship2,3 (also known as the Leavitt law). The Large Magellanic Cloud has traditionally served as the best galaxy with which to calibrate Cepheid period-luminosity relations, and as a result has become the best anchor point for the cosmic distance scale4,5. Eclipsing binary systems composed of late-type stars offer the most precise and accurate way to measure the distance to the Large Magellanic Cloud. Currently the limit of the precision attainable with this technique is about two per cent, and is set by the precision of the existing calibrations of the surface brightness-colour relation5,6. Here we report a calibration of the surface brightness-colour relation with a precision of 0.8 per cent. We use this calibration to determine a geometrical distance to the Large Magellanic Cloud that is precise to 1 per cent based on 20 eclipsing binary systems. The final distance is 49.59 ± 0.09 (statistical) ± 0.54 (systematic) kiloparsecs.

Acute mucosal reactions in patients with head and neck cancer. Three patterns of mucositis observed during radiotherapy.

PURPOSE: To investigate the individual pattern of acute mucosal radiation reactions (AMRR) in patients with head and neck cancer who were treated with radiotherapy alone. Reactions were evaluated daily on an individual basis according to the Dische scoring system. MATERIALS AND METHODS: Treatment of 87 head and neck cancer patients comprised either conventional fractionation- (CF; n = 33), accelerated fractionation (AF; n = 33), hyperfractionated- (HPEFX; n = 12) or hypofractionated (HPOFX; n = 9) radiotherapy with radical intent. Daily evaluation of AMRR progression was performed prospectively using a modified, morphologically functional Dische scoring system. The daily sums of the score parameters were subsequently used to construct an individual AMRR course curve for each patient. RESULTS: A latency period ranging from 3 to 14 days between the start of radiotherapy and the occurrence of the first AMRR symptom was observed in all patients. Based on the three different shapes of AMRR course curve observed during radiotherapy, three types of AMRR course can be described: (1) a continual increase in AMRR intensity until the completion of radiotherapy; (2) the incidence of a plateau phase following the increase in AMRR (increase-plateau course) and (3) decreasing AMRR intensity with a healing phase. A continual increase in AMRR intensity was observed in about 25 % of CF and AF patients and in more than 50 % of HPOFX treatments. This type of reaction was not observed in the HPEFX group. The increase-plateau course was noted in the majority of AF and CF patients; in almost half of those treated with HPOFX and in all HPEFX patients. A decreasing AMRR intensity course was observed in 23 % of all patients, although not observed at all in the HPEFX and HPOFX fractionation groups. CONCLUSION: The course of AMRR during radiotherapy can differ between individual patients. After the initial increase in AMRR intensity, a stabilization of the reaction--visible as a plateau phase on the course curve--is observed in the majority of patients. A proportion of the irradiated patients experience a continual increase in AMRR intensity up until the end of radiotherapy. A further group of patients exists in whom signs of AMRR healing are observed during the final stages of radiotherapy.

An eclipsing-binary distance to the Large Magellanic Cloud accurate to two per cent.

In the era of precision cosmology, it is essential to determine the Hubble constant to an accuracy of three per cent or better. At present, its uncertainty is dominated by the uncertainty in the distance to the Large Magellanic Cloud (LMC), which, being our second-closest galaxy, serves as the best anchor point for the cosmic distance scale. Observations of eclipsing binaries offer a unique opportunity to measure stellar parameters and distances precisely and accurately. The eclipsing-binary method was previously applied to the LMC, but the accuracy of the distance results was lessened by the need to model the bright, early-type systems used in those studies. Here we report determinations of the distances to eight long-period, late-type eclipsing systems in the LMC, composed of cool, giant stars. For these systems, we can accurately measure both the linear and the angular sizes of their components and avoid the most important problems related to the hot, early-type systems. The LMC distance that we derive from these systems (49.97 ± 0.19 (statistical) ± 1.11 (systematic) kiloparsecs) is accurate to 2.2 per cent and provides a firm base for a 3-per-cent determination of the Hubble constant, with prospects for improvement to 2 per cent in the future.

Acute mucosal radiation reactions in patients with head and neck cancer. Patterns of mucosal healing on the basis of daily examinations.

PURPOSE: The goal of this research was to evaluate the healing processes of acute mucosal radiation reactions (AMRR) in patients with head and neck cancer. MATERIALS AND METHODS: In 46 patients with oral and oropharyngeal cancer patients irradiated with conventional (n = 25) and accelerated (n = 21) dose fractionation AMRR was evaluated daily during and after radiotherapy. Complex of morphological and functional symptoms according to the Dische score were collected daily until complete healing. RESULTS: Duration of healing after the end of radiotherapy ranged widely (12-70 days). It was on the average 8 days longer for accelerated than for conventional radiotherapy (p = 0.016). Duration of dysphagia was also longer for accelerated irradiation (11 days, p = 0.027). Three types of morphological symptoms were observed as the last symptom at the end of AMRR healing: spotted and confluent mucositis, erythema, and edema. Only a slight correlation between healing duration and area of irradiation fields (r = 0.23) was noted. In patients with confluent mucositis, two morphological forms of mucosal healing were observed, i.e., marginal and spotted. The spotted form was noted in 71% of patients undergoing conventional radiotherapy and in 38% of patients undergoing accelerated radiotherapy. The symptoms of mucosal healing were observed in 40% patients during radiotherapy. CONCLUSION: The wide range of AMRR healing reflects individual potential of mucosa recovery with longer duration for accelerated radiotherapy. Two morphological forms of confluent mucositis healing were present: marginal and spotted. Healing of AMRR during radiotherapy can be observed in a significant proportion of patients.

RR-Lyrae-type pulsations from a 0.26-solar-mass star in a binary system.

RR Lyrae pulsating stars have been extensively used as tracers of old stellar populations for the purpose of determining the ages of galaxies, and as tools to measure distances to nearby galaxies. There was accordingly considerable interest when the RR Lyrae star OGLE-BLG-RRLYR-02792 (referred to here as RRLYR-02792) was found to be a member of an eclipsing binary system, because the mass of the pulsator (hitherto constrained only by models) could be unambiguously determined. Here we report that RRLYR-02792 has a mass of 0.26 solar masses M[symbol see text] and therefore cannot be a classical RR Lyrae star. Using models, we find that its properties are best explained by the evolution of a close binary system that started with M[symbol see text] and 0.8M[symbol see text]stars orbiting each other with an initial period of 2.9 days. Mass exchange over 5.4 billion years produced the observed system, which is now in a very short-lived phase where the physical properties of the pulsator happen to place it in the same instability strip of the Hertzsprung-Russell diagram as that occupied by RR Lyrae stars. We estimate that only 0.2 per cent of RR Lyrae stars may be contaminated by systems similar to this one, which implies that distances measured with RR Lyrae stars should not be significantly affected by these binary interlopers.

The influence of corporate and political interests on models of illness in the evolution of the DSM.

The diagnostic and statistical manual of mental disorders (DSM) is an evolving document that serves the many mental health care disciplines as the primary reference guide for classifying mental disorders. While the successive framers of the DSM have attempted to base it on scientific evidence, political and economic factors have also shaped the conceptualization of mental illness. These economic and institutional forces have reinforced the DSM's use of a medical model in understanding psychopathology. Though the scientific evidence for a medical model is mixed and evidence for other types of conceptualizations have been given less attention, the medical model provides for reliable diagnoses that allot diverse benefits to treatment providers and researchers, as well as to the pharmaceutical and healthcare industries. This article will outline the development of a medical model of mental illness, highlighting connections between this model and corporate and political interests, and will show how this model relates to the various revisions of, and developments within, the DSM. Such an analysis is especially relevant today as the field looks towards the publication of the newest revision of the DSM and attempts to understand and integrate its proposed changes into current treatment, theory, and research.

The dynamical mass of a classical Cepheid variable star in an eclipsing binary system.

Stellar pulsation theory provides a means of determining the masses of pulsating classical Cepheid supergiants-it is the pulsation that causes their luminosity to vary. Such pulsational masses are found to be smaller than the masses derived from stellar evolution theory: this is the Cepheid mass discrepancy problem, for which a solution is missing. An independent, accurate dynamical mass determination for a classical Cepheid variable star (as opposed to type-II Cepheids, low-mass stars with a very different evolutionary history) in a binary system is needed in order to determine which is correct. The accuracy of previous efforts to establish a dynamical Cepheid mass from Galactic single-lined non-eclipsing binaries was typically about 15-30% (refs 6, 7), which is not good enough to resolve the mass discrepancy problem. In spite of many observational efforts, no firm detection of a classical Cepheid in an eclipsing double-lined binary has hitherto been reported. Here we report the discovery of a classical Cepheid in a well detached, double-lined eclipsing binary in the Large Magellanic Cloud. We determine the mass to a precision of 1% and show that it agrees with its pulsation mass, providing strong evidence that pulsation theory correctly and precisely predicts the masses of classical Cepheids.

[The effectiveness of combined treatment for laryngeal cancer in Silesia region during the years 1987-1996]. / Ocena wyników skojarzonego leczenia raka krtani w materiale klinicznym Instytutu Onkologii w Gliwicach w latach 1987-1996.

Between 1987-1996, 484 patients with laryngeal cancer were treated by surgery and adjuvant radiotherapy. The 25-30% therapeutic gain was noted when to compare the first period of the study (1987-1992) with the second (1993-1996). The increment of effectiveness of combined treatment for larynx cancer is probably the result of better quality of surgical procedures and individualization of radiation treatment.

[Head and neck lymph node metastases from unknown primary site]. / Przerzuty do wezlów chlonnych regionu glowy i szyi z nieznanego ogniska pierwotnego.

The aim of this paper was to evaluate the group of 50 patients with cervical nodes metastases from unknown primary site treated between 1980-1995 in Maria Sk_odowska-Curie Memorial Institute of Oncology in Gliwice. There were 42 males and 8 females ranging in age from 26 to 85 years (median 60). 24 patients underwent combined therapy (surgery with postoperative radiotherapy), 22 underwent radiotherapy. Only 4 patients were treated with surgery alone. 3-years DFS rates were 59% in group treated with combined method, and 10% in group treated only with radiation therapy (p = 0.003). After a median follow up of 39 months 10 primary tumors were discovered--8 in head and neck region, 2 in lower respiratory tracts. DFS rate in group with discovered primary tumors was 40%.

Randomized clinical trial on 7-day-continuous accelerated irradiation (CAIR) of head and neck cancer - report on 3-year tumour control and normal tissue toxicity.

PURPOSE: To evaluate tumour and normal tissues 3-year response to 7-day-a-week continuous accelerated irradiation (CAIR) compared to a conventional treatment (5 days per week) in a randomized trial. MATERIALS AND METHODS: One hundred patients with squamous cell carcinoma of the head and neck in stage T(2-4)N(0-1)M(0) were entered into the trial between December 1, 1993 and June 30, 1996. Dose per fraction of 2.0 Gy (to the end of 1994), and 1.8 Gy (since January 1, 1995) was the same in both arms and delivered once a day at regular 24-h intervals to total dose in the range of 66-72 Gy (depending on tumour stage). The only difference was overall treatment time being 5 weeks in the CAIR and 7 weeks in control arm. RESULTS: Actuarial 3-year local tumour control was 82% in the CAIR and 37% in the control group (P<0.0001) with reduction in local recurrence rate of 83%. Actuarial 3-year overall survival was 78 and 32% (P<0.0001), respectively. Confluent mucositis was significantly more severe and lasted longer in the CAIR than in control arm. After 2.0 Gy fractions five of 23 patients (22%) in the CAIR developed early necroses over a period of 2-4 months of follow-up which can be considered as a consequential to severe protracted acute mucosal reactions (CLE). For this reason dose per fraction was lowered to 1. 8 Gy and the CLE was not observed again until now. Thus the overall rate of CLE decreased to 10%. CONCLUSIONS: The gain in tumour control is likely the effect of shortening of overall treatment time by 14 days and regular continuous dose delivery during the whole course of radiation therapy including weekends. A 7-day schedule produces more severe acute mucosal reactions lasting longer than in conventional fractionation, however tolerable by patients. Relatively high rate (22%) of CLE in the 7-day arm observed during the first year of the study was eliminated by decreasing dose per fraction from 2.0 Gy to 1.8 Gy.

Randomized clinical trial on accelerated 7 days per week fractionation in radiotherapy for head and neck cancer. Preliminary report on acute toxicity.

PURPOSE: Toxicity of an accelerated 7 days per week fractionation schedule (arm A) was evaluated and compared with a conventional 5 days per week treatment (arm B) in a randomized trial. MATERIALS AND METHODS: Forty-four patients with squamous cell carcinoma of the head and neck in stage T2-4Nzero-1Mzero were included in the study. Total dose and dose per fraction of 2.0 Gy given once-a-day at 24 h intervals were the same in both arms of the trial. The only difference was the overall treatment time being 5 weeks in arm A and 7 weeks in arm B. RESULTS: Analysis of severe mucosal reactions shows significant difference between arm A and B, with regard to both maximum score and duration of severe mucositis. Confluent mucositis (score > 15 according to the Dische system) lasting longer than 3 weeks developed in 48% of patients in arm A and only in 5% in arm B. In group A seven (30%) late effects (osteo- and soft tissue necrosis) occurred during 7-12 month follow-up with two reactions (10%) in group B being suspected as late effects. There was significant association between acute reactions and late effects in arm A, suggesting that the late effects are consequential. CONCLUSION: The high incidence of severe acute reactions and consequential late effects suggests that the accelerated treatment in arm A (using daily fractions of 2.0 Gy, 7 days per week) gives unacceptable toxicity.

Sequential combination of radio-chemotherapy (5-fluorouracil, cis-platinum and irradiation) in the management of locally advanced head and neck cancers.

Thirty-seven previously untreated patients with advanced, inoperable head and neck were treated with a sequential courses combining hypofractionated irradiation with chemotherapy (5-fluorouracil and cis-platinum). Each course was repeated every 4 weeks. Tumor response was evaluated and for 15 patients (41%) with a partial or complete regression after 3 radio-chemotherapy courses conventional radiotherapy was added. Eleven percent of all patients were in complete remission at the end of a treatment. This tumor response rate and the 50% rate of pain subside after first course for symptomatic patients contributed for a good palliative effect in the present study. However, the median survival of 7.2 months was considered unsatisfactory.

Acute mucositis in the stimulated oral mucosa of patients during radiotherapy for head and neck cancer.

In 16 patients treated for squamous cell carcinoma of the oral cavity or oropharynx with an accelerated split course regimen, acute mucosal reactions were significantly less in the left buccal mucosa which had been repeatedly painted with 2% silver-nitrate solution for several days before radiotherapy than in the unpainted right buccal mucosa.

Hyperfractionated radiotherapy for Burkitt-type lymphoma. Radiobiological aspects.

A case of Burkitt-type lymphoma treated by accelerated hyperfractionated irradiation combined with the COP chemotherapy is presented. The effectiveness of treatment was evaluated on the basis of the growth curve and the radiobiological aspects are discussed. During the treatment, the initial volume doubling time (Td) of 15 days was shortened to 4.5 days suggesting accelerated tumor growth. From dose response curve estimated for clinical data taken from literature, an effDo of 1.37 Gy was calculated. Surviving fraction after 58 Gy given in the twice-a-day regimen (b. i. d.) was 10(-19) suggesting local tumor control. However, only partial remission was observed. This nonradical effect may likely result in accelerated repopulation of surviving tumor clonogenic cells. This suggests that such a fast growing tumor as Burkitt-type lymphoma (Tpot = 1 day) should be irradiated using three instead two fractions per day combined with adjuvant or concomitant chemotherapy with a short intervals between cycles.

Assignment report; Republic of Malawi; Ministry of Health

A review of the managerial set-up of the Ministry of Health with recommendations for changes