Statistical properties of subgroups of free groups

The usual way to investigate the statistical properties of finitely generated subgroups of free groups, and of finite presentations of groups, is based on the so-called word-based distribution: subgroups are generated (finite presentations are determined) by randomly chosen k-tuples of reduced words, whose maximal length is allowed to tend to infinity. In this paper we adopt a different, though equally natural point of view: we investigate the statistical properties of the same objects, but with respect to the so-called graph-based distribution, recently introduced by Bassino, Nicaud and Weil. Here, subgroups (and finite presentations) are determined by randomly chosen Stallings graphs whose number of vertices tends to infinity. Our results show that these two distributions behave quite differently from each other, shedding a new light on which properties of finitely generated subgroups can be considered frequent or rare. For example, we show that malnormal subgroups of a free group are negligible in the raph-based distribution, while they are exponentially generic in the word-based distribution. Quite surprisingly, a random finite presentation generically presents the trivial group in this new distribution, while in the classical one it is known to generically present an infinite hyperbolic group.

Continuous Sunitinib treatment in patients with advanced hepatocellular carcinoma: a Swiss Group for Clinical Cancer Research (SAKK) and Swiss Association for the Study of the Liver (SASL) multicenter phase II trial (SAKK 77/06).

BACKGROUND: Sunitinib (SU) is a multitargeted tyrosine kinase inhibitor with antitumor and antiangiogenic activity. The objective of this trial was to demonstrate antitumor activity of continuous SU treatment in patients with hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Key eligibility criteria included unresectable or metastatic HCC, no prior systemic anticancer treatment, measurable disease, and Child-Pugh class A or mild Child-Pugh class B liver dysfunction. Patients received 37.5 mg SU daily until progression or unacceptable toxicity. The primary endpoint was progression-free survival at 12 weeks (PFS12). RESULTS: Forty-five patients were enrolled. The median age was 63 years; 89% had Child-Pugh class A disease and 47% had distant metastases. PFS12 was rated successful in 15 patients (33%; 95% confidence interval, 20%-47%). Over the whole trial period, one complete response and a 40% rate of stable disease as the best response were achieved. The median PFS duration, disease stabilization duration, time to progression, and overall survival time were 1.5, 2.9, 1.5, and 9.3 months, respectively. Grade 3 and 4 adverse events were infrequent. None of the 33 deaths were considered drug related. CONCLUSION: Continuous SU treatment with 37.5 mg daily is feasible and has moderate activity in patients with advanced HCC and mild to moderately impaired liver dysfunction. Under this trial design (>13 PFS12 successes), the therapy is considered promising. This is the first trial describing the clinical effects of continuous dosing of SU in HCC patients on a schedule that is used in an ongoing, randomized, phase III trial in comparison with the current treatment standard, sorafenib (ClinicalTrials.gov identifier, NCT00699374).

Short-course thymoglobulin induction and steroid-free immunosuppressive regimen in renal transplantation

Purpose: Optimal induction and maintenance immunosuppressive therapies in renal transplantation are still a matter of debate.Chronic corticosteroid usage is a major cause of morbidity but steroid-free immunosuppression (SF) can result in unacceptably high rates of acute rejection and even graft loss. Methods and materials: We have conducted a prospective openlabelled clinical trial in the Geneva-Lausanne Transplant Network from March 2005 to May 2008. 20 low immunological risk (<20% PRA, no DSA) adult recipients of a primary kidney allograft received a 4-day course of thymoglobulin (1.5 mg/kg/d) with methylprednisolone and maintenance based immunosuppression of tacrolimus and entericcoated mycophenolic acid (MPA). The control arm consisted of 16 matched recipients treated with basiliximab induction, tacrolimus, mycophenolate mofetil and corticosteroids. Primary endpoints were the percentage of recipients not taking steroids and the percentage of rejection-free recipients at 12 months.Secondary end points were allograft survival at 12 months and significant thymoglobulin and/or other drugs side effects. Results: In the SF group, 85% of the kidney recipients remained steroid-free at 12 months. The 3 cases of steroids introduction were due to one acute tubulo-interstitial rejection occurring at day 11, one tacrolimus withdrawal due to thrombotic microangiopathy and one MPA withdrawal because of multiple sinusitis and CMV reactivations. No BK viremia was detected nor CMV disease. The 6 CMV negative patients who received a positive CMV allograft had a symptomatic primoinfection after their 6-month course valgancyclovir prophylaxis. In the steroid-based group, 3 acute rejection episodes (acute humoral rejection, acute tubulointerstitial Banff IA and vascular Banff IIA) occurred in 2 recipients, 3 BK virus nephropathies were diagnosed between 45 and 135 days post transplant No side effects were associated with thymoglobulin infusion.In the SF group, 4 recipients presented severe leukopenia or agranulocytosis and one recipient had febrile hepatitis leading to transient MPA withdrawal. Discontinuation of MPA was needed in 2 patients for recurrent sinusitis and CMV reactivations. Patient and graft survival was 100% in both groups at 12 month follow-up. Conclusion: Steroid-free with short-course thymoglobulin induction therapy was a safe protocol in low-risk renal transplant recipients. Lower rates of acute rejection and BK virus infections episodes were seen compared to the steroid-based control group. A longer follow-up will be needed to determine whether this SF immunosuppressive regimen will result in higher graft and patient survival.

Penicillin tolerance among Beta-hemolytic streptococci and production of the group carbohydrates, hemolysins, hyaluronidases and deoxyribonucleases

Penicillin tolerance among 67 strains of beta-hemolytic streptococci was examined by determining the ratio of the minimal bactericidal concentration to the minimal inhibitory concentration as 32 or greater. Tolerance was demonstrated in 15 group A strains and in 11,7, and 4 of groups B, C and G, respectively. Thereafter the effects of a subminimal inhibitory concentration (1/2MIC) of penicillin on the bacterial products of four tolerant and four nontolerant strains (two of each Lancefield group) were analyzed and compared. The antibiotic caused a marked increase in the expression of the group carbo-hydrates for strains of group B. Penicillin was found to reduce the cell-bound hemolysin activities of the four tolerant strains and to increase the activity of the other (free) form of nontolerant groups A, C and G hemolysins. Penicillin caused an increase in the extracellular hyaluronidase activities of one group A and groups B, C and G streptococci. With added antibiotic the production of deoxyribonuclease by tolerant groups A, C and G was greatly enhanced and that of the group B streptococcus was arrested.

Treatment of localised resectable neuroblastoma. Results of the LNESG1 study by the SIOP Europe Neuroblastoma Group.

Main objective of this study was to confirm that surgery alone is an effective and safe treatment for localised resectable neuroblastoma except stage 2 with amplified MYCN gene (MYCNA). Of 427 eligible stages 1-2 patients, 411 had normal MYCN and 16 had MYCNA. Of the 288 stage 1 patients with normal MYCN, 1 died of complications and 16 relapsed, 2 of whom died; 5-year relapse-free survival (RFS) and overall survival (OS) rates were 94.3% (95% confidence interval (CI): 91.6-97) and 98.9% (95% CI: 97.7-100), respectively. Of the 123 stage 2 patients with normal MYCN, 1 died of sepsis and 22 relapsed, 8 of whom died (RFS 82.8%, 95% CI: 76.2-89.5; OS 93.2%, 95% CI: 88.7-97.8). In stage 2, OS and RFS were worse for patients with elevated LDH and unfavourable histopathology. Of 16 children with MYCNA, 7 were stage 1 (5 relapses and 4 deaths) and 9 were stage 2 (3 relapses and 2 deaths) patients. In conclusion, surgery alone yielded excellent OS for both stage 1 and 2 neuroblastoma without MYCNA, although stage 2 patients with unfavourable histopathology and elevated LDH suffered a high number of relapses. Both stage 1 and 2 patients with MYCNA were at greater risk of relapse.

Pelvic organ prolapse surgery with and without tension-free vaginal tape in women with occult or asymptomatic urodynamic stress incontinence: a randomised controlled trial.

INTRODUCTION: We set out to determine if insertion of a retropubic tension-free vaginal tape (TVT) sling at the time of pelvic organ prolapse surgery improves continence outcomes in women with pre-operative occult stress incontinence (OSI) or asymptomatic urodynamic stress incontinence (USI). METHODS: We conducted a randomised controlled study of prolapse surgery with or without a TVT midurethral sling. The pre- and post-operative assessment at 6 months included history, physical examination and urodynamic testing. Quality of life (QOL) and treatment success was assessed with the UDI-6 SF, IIQ-7 SF and a numerical success score. The primary outcome was symptomatic stress urinary incontinence (SUI) requiring continence surgery (TVT) at 6 months. Long-term follow-up continued to a minimum of 24 months. Secondary outcomes were quality of life parameters. RESULTS: Eighty women received prolapse surgery alone (n = 43) or prolapse surgery with concurrent TVT (n = 37). Six months following prolapse surgery 3 out of 43 (7 %) patients in the no TVT group requested sling surgery compared with 0 out of 37 (0 %) in the TVT group (ARR 7 % [95 %CI: 3 to 19 %], p = 0.11). After 24 months there was one further participant in the no TVT group who received a TVT for treatment of SUI compared with none in the TVT group (4 out of 43, 9.3 % versus 0 out of 37; ARR 9.3 % [95 %CI: -1 to 22 %], p = 0.06). Both groups showed improvement in QOL difference scores for within-group analysis, without difference between groups. CONCLUSION: These results support a policy that routine insertion of a sling in women with OSI at the time of prolapse repair is questionable and should be subject to shared decision-making between clinician and patient.

Subjective Memory Deficits in People with and without Dementia: Findings from the 10/66 Dementia Research Group Pilot Studies in Low- and Middle-Income Countries

OBJECTIVES To compare subjective memory deficit (SMD) in older adults with and without dementia or depression across multiple centers in low- and middle-income countries (LAMICs). DESIGN Secondary analysis of data from 23 case control studies. SETTING Twenty-three centers in India, Southeast Asia (including China), Latin America and the Caribbean, Nigeria, and Russia. PARTICIPANTS Two thousand six hundred ninety-two community-dwelling people aged 60 and older in one of three groups: people with dementia, people with depression, and controls free of dementia and depression. MEASUREMENTS SMD was derived from the Geriatric Mental State examination. RESULTS Median SMD frequency was lowest in participants without dementia (26.2%) and higher in those with depression (50.0%) and dementia (66.7%). Frequency of SMD varied between centers. Depression and dementia were consistently associated with SMD. Older age and hypochondriasis were associated with SMD only in subjects without dementia. In those with dementia, SMD was associated with better cognitive function, whereas the reverse was the case in controls. CONCLUSION Associations with SMD may differ between subjects with and without dementia living in LAMICs.

Detection of coronary stenoses with contrast enhanced, three-dimensional free breathing coronary MR angiography using the gadolinium-based intravascular contrast agent gadocoletic acid (B-22956).

PURPOSE: To determine the diagnostic value of the intravascular contrast agent gadocoletic acid (B-22956) in three-dimensional, free breathing coronary magnetic resonance angiography (MRA) for stenosis detection in patients with suspected or known coronary artery disease. METHODS: Eighteen patients underwent three-dimensional, free breathing coronary MRA of the left and right coronary system before and after intravenous application of a single dose of gadocoletic acid (B-22956) using three different dose regimens (group A 0.050 mmol/kg; group B 0.075 mmol/kg; group C 0.100 mmol/kg). Precontrast scanning followed a coronary MRA standard non-contrast T2 preparation/turbo-gradient echo sequence (T2Prep); for postcontrast scanning an inversion-recovery gradient echo sequence was used (real-time navigator correction for both scans). In pre- and postcontrast scans quantitative analysis of coronary MRA data was performed to determine the number of visible side branches, vessel length and vessel sharpness of each of the three coronary arteries (LAD, LCX, RCA). The number of assessable coronary artery segments was determined to calculate sensitivity and specificity for detection of stenosis > or = 50% on a segment-to-segment basis (16-segment-model) in pre- and postcontrast scans with x-ray coronary angiography as the standard of reference. RESULTS: Dose group B (0.075 mmol/kg) was preferable with regard to improvement of MR angiographic parameters: in postcontrast scans all MR angiographic parameters increased significantly except for the number of visible side branches of the left circumflex artery. In addition, assessability of coronary artery segments significantly improved postcontrast in this dose group (67 versus 88%, p < 0.01). Diagnostic performance (sensitivity, specificity, accuracy) was 83, 77 and 78% for precontrast and 86, 95 and 94% for postcontrast scans. CONCLUSIONS: The use of gadocoletic acid (B-22956) results in an improvement of MR angiographic parameters, asssessability of coronary segments and detection of coronary stenoses > or = 50%.

Assessment of Therapeutic Response of Plasmodium vivax and Plasmodium falciparum to Chloroquine in a Malaria Transmission Free Area in Colombia

In order to determine the frequency of therapeutic failures to chloroquine (CQ) in patients with malaria due to either Plasmodium falciparum or P. vivax, and to explore the usefulness of a malaria-free city as a sentinel site to monitor the emergence of drug resistance, 53 patients (44 infected with P. vivax and 9 with P. falciparum) were evaluated at the Laboratory of Parasitology, Universidad del Valle in Cali, Colombia. Patients received 25 mg/kg of CQ divided in three doses over 48 h; they were followed during 28 days according to WHO/PAHO protocols. While therapeutic failures to CQ in the P. vivax group were not detected, the proportion of therapeutic failures in the P. falciparum group was high (78%) and consistent with the reports from endemic areas in Colombia. The diverse origin of cases presenting therapeutic failure confirmed that P. falciparum resistant to CQ is widespread in Colombia, and further supports the change in the national antimalarial drug scheme. Monitoring of drug resistance in malaria free areas would be useful to identify sites requiring efficacy evaluation, and in some situations could be the most appropriate alternative to collect information from endemic areas where therapeutic efficacy studies are not feasible.

Autologous Stem Cell Transplantation (ASCT) for Enteropathy-Associated T-Cell Lymphoma (EATL): Final Analysis of a Retrospective Study On the Behalf of Lymphoma Working Party (LWP) of the European Group for Blood and Marrow Transplantation (EBMT).

Background: EATL is a rare subtype of peripheral T-cell lymphomas characterized by primarily intestinal localization and a frequent association with celiac disease. The prognosis is considered to be poor with conventional chemotherapy. Limited data is available on the efficacy of ASCT in this lymphoma subtype. Primary objective: was to study the outcome of ASCT as a consolidation or salvage strategy for EATL. The primary endpoint was overall survival (OS) and progression-free survival (PFS). Eligible patients were > 18 years who had received ASCT between 2000-2010 for EATL that was confirmed by review of written histopathology reports, and had sufficient information on disease history and follow-up available. The search strategy used the EBMT database to identify patients potentially fulfilling the eligibility criteria. An additional questionnaire was sent to individual transplant centres to confirm histological diagnosis (histopathology report or pathology review) as well as updated follow-up data. Patients and transplant characteristics were compared between groups using X2 test or Fisher's exact test for categorical variables and t-test or Mann-Whiney U-test for continuous variables. OS and PFS were estimated using the Kaplan-Meier product-limit estimate and compared by the log-rank test. Estimates for non-relapse mortality (NRM) and relapse or progression were calculated using cumulative incidence rates to accommodate competing risk and compared to Gray's test. Results: Altogether 138 patients were identified. Updated follow-up data was received from 74 patients (54 %) and histology report from 54 patients (39 %). In ten patients the diagnosis of EATL could not be adequately verified. Thus the final analysis included 44. There were 24 males and 20 females with a median age of 56 (35-72) years at the time of transplant. Twenty-five patients (57 %) had a history of celiac disease. Disease stage was I in nine patients (21 %), II in 14 patients (33 %) and IV in 19 patients (45 %). Twenty-four patients (55 %) were in the first CR or PR at the time of transplant. BEAM was used as a high-dose regimen in 36 patients (82 %) and all patients received peripheral blood grafts. The median follow-up for survivors was 46 (2-108) months from ASCT. Three patients died early from transplant-related reasons translating into a 2-year non-relapse mortality of 7 %. Relapse incidence at 4 years after ASCT was 39 %, with no events occurring beyond 2.5 years after ASCT. PFS and OS were 54 % and 59 % at four years, respectively. There was a trend for better OS in patients transplanted in the first CR or PR compared to more advanced disease status (70 % vs. 43 %, p=0.053). Of note, patients with a history of celiac disease had superior PFS (70 % vs. 35 %, p=0.02) and OS (70 % vs. 45 %, p=0.052) whilst age, gender, disease stage, B-symptoms at diagnosis or high-dose regimen were not associated with OS or PFS. Conclusions: This study shows for the first time in a larger patient sample that ASCT is feasible in selected patients with EATL and can yield durable disease control in a significant proportion of the patients. Patients transplanted in first CR or PR appear to do better than those transplanted later. ASCT should be considered in EATL patients responding to initial therapy.

Outcome after relapse of acute lymphoblastic leukemia in adult patients included in four consecutive risk-adapted trials by the PETHEMA Study Group

BACKGROUND About one half of adults with acute lymphoblastic leukemia are not cured of the disease and ultimately die. The objective of this study was to explore the factors influencing the outcome of adult patients with relapsed acute lymphoblastic leukemia. DESIGN AND METHODS. We analyzed the characteristics, the outcome and the prognostic factors for survival after first relapse in a series of 263 adult patients with acute lymphoblastic leukemia (excluding those with mature B-cell acute lymphoblastic leukemia) prospectively enrolled in four consecutive risk-adapted PETHEMA trials. RESULTS. The median overall survival after relapse was 4.5 months (95% CI, 4-5 months) with a 5-year overall survival of 10% (95% CI, 8%-12%); 45% of patients receiving intensive second-line treatment achieved a second complete remission and 22% (95% CI, 14%-30%) of them remained disease free at 5 years. Factors predicting a good outcome after rescue therapy were age less than 30 years (2-year overall survival of 21% versus 10% for those over 30 years old; P<0.022) and a first remission lasting more than 2 years (2-year overall survival of 36% versus 17% among those with a shorter first remission; P<0.001). Patients under 30 years old whose first complete remission lasted longer than 2 years had a 5-year overall survival of 38% (95% CI, 23%-53%) and a 5-year disease-free survival of 53% (95% CI, 34%-72%). CONCLUSIONS The prognosis of adult patients with acute lymphoblastic leukemia who relapse is poor. Those aged less than 30 years with a first complete remission lasting longer than 2 years have reasonable possibilities of becoming long-term survivors while patients over this age or those who relapse early cannot be successfully rescued using the therapies currently available.

Event-free survival at 24 months is a robust end point for disease-related outcome in diffuse large B-cell lymphoma treated with immunochemotherapy.

PURPOSE: Studies of diffuse large B-cell lymphoma (DLBCL) are typically evaluated by using a time-to-event approach with relapse, re-treatment, and death commonly used as the events. We evaluated the timing and type of events in newly diagnosed DLBCL and compared patient outcome with reference population data. PATIENTS AND METHODS: Patients with newly diagnosed DLBCL treated with immunochemotherapy were prospectively enrolled onto the University of Iowa/Mayo Clinic Specialized Program of Research Excellence Molecular Epidemiology Resource (MER) and the North Central Cancer Treatment Group NCCTG-N0489 clinical trial from 2002 to 2009. Patient outcomes were evaluated at diagnosis and in the subsets of patients achieving event-free status at 12 months (EFS12) and 24 months (EFS24) from diagnosis. Overall survival was compared with age- and sex-matched population data. Results were replicated in an external validation cohort from the Groupe d'Etude des Lymphomes de l'Adulte (GELA) Lymphome Non Hodgkinien 2003 (LNH2003) program and a registry based in Lyon, France. RESULTS: In all, 767 patients with newly diagnosed DLBCL who had a median age of 63 years were enrolled onto the MER and NCCTG studies. At a median follow-up of 60 months (range, 8 to 116 months), 299 patients had an event and 210 patients had died. Patients achieving EFS24 had an overall survival equivalent to that of the age- and sex-matched general population (standardized mortality ratio [SMR], 1.18; P = .25). This result was confirmed in 820 patients from the GELA study and registry in Lyon (SMR, 1.09; P = .71). Simulation studies showed that EFS24 has comparable power to continuous EFS when evaluating clinical trials in DLBCL. CONCLUSION: Patients with DLBCL who achieve EFS24 have a subsequent overall survival equivalent to that of the age- and sex-matched general population. EFS24 will be useful in patient counseling and should be considered as an end point for future studies of newly diagnosed DLBCL.

Allogeneic stem cell transplantation after reduced intensity conditioning in patients with relapsed or refractory Hodgkin's lymphoma. Results of the HDR-ALLO study - a prospective clinical trial by the Grupo Español de Linfomas/Trasplante de Médula Osea (GEL/TAMO) and the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation.

BACKGROUND Although Hodgkin's lymphoma is a highly curable disease with modern chemotherapy protocols, some patients are primary refractory or relapse after first-line chemotherapy or even after high-dose therapy and autologous stem cell transplantation. We investigated the potential role of allogeneic stem cell transplantation in this setting. DESIGN AND METHODS In this phase II study 92 patients with relapsed Hodgkin's lymphoma and an HLA-identical sibling, a matched unrelated donor or a one antigen mismatched, unrelated donor were treated with salvage chemotherapy followed by reduced intensity allogeneic transplantation. Fourteen patients showed refractory disease and died from progressive lymphoma with a median overall survival after trial entry of 10 months (range, 6-17). Seventy-eight patients proceeded to allograft (unrelated donors, n=23). Fifty were allografted in complete or partial remission and 28 in stable disease. Fludarabine (150 mg/m(2) iv) and melphalan (140 mg/m(2) iv) were used as the conditioning regimen. Anti-thymocyte globulin was additionally used as graft-versus-host-disease prophylaxis for recipients of grafts from unrelated donors. RESULTS The non-relapse mortality rate was 8% at 100 days and 15% at 1 year. Relapse was the major cause of failure. The progression-free survival rate was 47% at 1 year and 18% at 4 years from trial entry. For the allografted population, the progression-free survival rate was 48% at 1 year and 24% at 4 years. Chronic graft-versus-host disease was associated with a lower incidence of relapse. Patients allografted in complete remission had a significantly better outcome. The overall survival rate was 71% at 1 year and 43% at 4 years. CONCLUSIONS Allogeneic stem cell transplantation can result in long-term progression-free survival in heavily pre-treated patients with Hodgkin's lymphoma. The reduced intensity conditioning approach significantly reduced non-relapse mortality; the high relapse rate represents the major remaining challenge in this setting. The HDR-Allo trial was registered in the European Clinical Trials Database (EUDRACT, https://eudract.ema.europa.eu/) with number 02-0036.

Role of Kras Status in Patients with Metastatic Colorectal Cancer Receiving First-Line Chemotherapy plus Bevacizumab: A TTD Group Cooperative Study

BACKGROUND In the MACRO study, patients with metastatic colorectal cancer (mCRC) were randomised to first-line treatment with 6 cycles of capecitabine and oxaliplatin (XELOX) plus bevacizumab followed by either single-agent bevacizumab or XELOX plus bevacizumab until disease progression. An additional retrospective analysis was performed to define the prognostic value of tumour KRAS status on progression-free survival (PFS), overall survival (OS) and response rates. METHODOLOGY/PRINCIPAL FINDINGS KRAS data (tumour KRAS status and type of mutation) were collected by questionnaire from participating centres that performed KRAS analyses. These data were then cross-referenced with efficacy data for relevant patients in the MACRO study database. KRAS status was analysed in 394 of the 480 patients (82.1%) in the MACRO study. Wild-type (WT) KRAS tumours were found in 219 patients (56%) and mutant (MT) KRAS in 175 patients (44%). Median PFS was 10.9 months for patients with WT KRAS and 9.4 months for patients with MT KRAS tumours (p=0.0038; HR: 1.40; 95% CI:1.12-1.77). The difference in OS was also significant: 26.7 months versus 18.0 months for WT versus MT KRAS, respectively (p=0.0002; HR: 1.55; 95% CI: 1.23-1.96). Univariate and multivariate analyses showed that KRAS was an independent variable for both PFS and OS. Responses were observed in 126 patients (57.5%) with WT KRAS tumours and 76 patients (43.4%) with MT KRAS tumours (p=0.0054; OR: 1.77; 95% CI: 1.18-2.64). CONCLUSIONS/SIGNIFICANCE This analysis of the MACRO study suggests a prognostic role for tumour KRAS status in patients with mCRC treated with XELOX plus bevacizumab. For both PFS and OS, KRAS status was an independent factor in univariate and multivariate analyses.

Fat-free mass index and fat mass index percentiles in Caucasians aged 18-98 y.

OBJECTIVE: To determine reference values for fat-free mass index (FFMI) and fat mass index (FMI) in a large Caucasian group of apparently healthy subjects, as a function of age and gender and to develop percentile distribution for these two parameters. DESIGN: Cross-sectional study in which bioelectrical impedance analysis (50 kHz) was measured (using tetrapolar electrodes and cross-validated formulae by dual-energy X-ray absorptiometry in order to calculate FFMI (fat-free mass/height squared) and FMI (fat mass/height squared). SUBJECTS: A total of 5635 apparently healthy adults from a mixed non-randomly selected Caucasian population in Switzerland (2986 men and 2649 women), varying in age from 24 to 98 y. RESULTS: The median FFMI (18-34 y) were 18.9 kg/m(2) in young males and 15.4 kg/m(2) in young females. No difference with age in males and a modest increase in females were observed. The median FMI was 4.0 kg/m(2) in males and 5.5 kg/m(2) in females. From young to elderly age categories, FMI progressively rose by an average of 55% in males and 62% in females, compared to an increase in body mass index (BMI) of 9 and 19% respectively. CONCLUSIONS: Reference intervals for FFMI and FMI could be of practical value for the clinical evaluation of a deficit in fat-free mass with or without excess fat mass (sarcopenic obesity) for a given age category, complementing the classical concept of body mass index (BMI) in a more qualitative manner. In contrast to BMI, similar reference ranges seems to be utilizable for FFMI with advancing age, in particular in men.