Merging morphological and genetic evidence to assess hybridization in Western Eurasian late Pleistocene hominins.

Previous scientific consensus saw human evolution as defined by adaptive differences (behavioural and/or biological) and the emergence of Homo sapiens as the ultimate replacement of non-modern groups by a modern, adaptively more competitive group. However, recent research has shown that the process underlying our origins was considerably more complex. While archaeological and fossil evidence suggests that behavioural complexity may not be confined to the modern human lineage, recent palaeogenomic work shows that gene flow between distinct lineages (for example, Neanderthals, Denisovans, early H. sapiens) occurred repeatedly in the late Pleistocene, probably contributing elements to our genetic make-up that might have been crucial to our success as a diverse, adaptable species. Following these advances, the prevailing human origins model has shifted from one of near-complete replacement to a more nuanced view of partial replacement with considerable reticulation. Here we provide a brief introduction to the current genetic evidence for hybridization among hominins, its prevalence in, and effects on, comparative mammal groups, and especially how it manifests in the skull. We then explore the degree to which cranial variation seen in the fossil record of late Pleistocene hominins from Western Eurasia corresponds with our current genetic and comparative data. We are especially interested in understanding the degree to which skeletal data can reflect admixture. Our findings indicate some correspondence between these different lines of evidence, flag individual fossils as possibly admixed, and suggest that different cranial regions may preserve hybridization signals differentially. We urge further studies of the phenotype to expand our ability to detect the ways in which migration, interaction and genetic exchange have shaped the human past, beyond what is currently visible with the lens of ancient DNA.

Hyponatremia and osteoporosis: reappraisal of a novel association.

UNLABELLED: Age was a modifier of the independent association between hyponatremia and osteoporosis (OP). Risk of OP was the highest in the youngest age group as compared to older patients. A longer duration of hyponatremia revealed a similar association with OP in all anatomical sites. INTRODUCTION: Epidemiologic studies provide conflicting results on the relationship between hyponatremia and OP. Our aim is to test the modification effect of age on the relationship between hyponatremia and OP at various anatomical sites in a large patient population. METHODS: This is a cross-sectional observation of consecutive patients with available bone densitometry, demographic, clinical, and laboratory data from 2001 to 2013 at a single center. OP was defined as a bone mineral density of ≤2.5 standard deviations below the mean peak bone mass of young, healthy adults. Hyponatremia was defined as serum sodium ≤135 mmol/L. Multiple logistic regressions were used to calculate adjusted odds ratio (OR). RESULTS: Overall, 24,784 patients were included. There were 4549 males (18.4 %). Hyponatremia was present in 703 patients (2.8 %), femoral neck OP in 2603 (10.5 %), total hip OP in 1885 (7.5 %), and lumbar OP in 4830 (19.5 %). Total hip OP occurred in 17.6 % (n = 124) of patients with hyponatremia as compared to 6.6 % (n = 880) of patients with sodium level of "140-145" mmol/L (P < 0.001). After multivariable adjustments, hyponatremia was associated with 2.46-fold higher odds of total hip OP (95 % CI, 1.36 to 4.46) in age <55 years, 1.96-fold (1.13 to 3.41) in age 55 to 67 years, and 1.55-fold (1.13 to 2.12) in age >67 years (age-sodium category interaction P value = 0.002). CONCLUSIONS: Age appeared as a modifier of the independent association between hyponatremia and OP. Risk of OP was the highest in the youngest age group as compared to older patients.

The effect of lifestyle intervention and metformin on preventing or delaying diabetes among women with and without gestational diabetes: the Diabetes Prevention Program outcomes study 10-year follow-up.

CONTEXT: Gestational diabetes (GDM) confers a high risk of type 2 diabetes. In the Diabetes Prevention Program (DPP), intensive lifestyle (ILS) and metformin prevented or delayed diabetes in women with a history of GDM. OBJECTIVE: The objective of the study was to evaluate the impact of ILS and metformin intervention over 10 years in women with and without a history of GDM in the DPP/Diabetes Prevention Program Outcomes Study. DESIGN: This was a randomized controlled clinical trial with an observational follow-up. SETTING: The study was conducted at 27 clinical centers. PARTICIPANTS: Three hundred fifty women with a history of GDM and 1416 women with previous live births but no history of GDM participated in the study. The participants had an elevated body mass index and fasting glucose and impaired glucose tolerance at study entry. INTERVENTIONS: Interventions included placebo, ILS, or metformin. OUTCOMES MEASURE: Outcomes measure was diabetes mellitus. RESULTS: Over 10 years, women with a history of GDM assigned to placebo had a 48% higher risk of developing diabetes compared with women without a history of GDM. In women with a history of GDM, ILS and metformin reduced progression to diabetes compared with placebo by 35% and 40%, respectively. Among women without a history of GDM, ILS reduced the progression to diabetes by 30%, and metformin did not reduce the progression to diabetes. CONCLUSIONS: Women with a history of GDM are at an increased risk of developing diabetes. In women with a history of GDM in the DPP/Diabetes Prevention Program Outcomes Study, both lifestyle and metformin were highly effective in reducing progression to diabetes during a 10-year follow-up period. Among women without a history of GDM, lifestyle but not metformin reduced progression to diabetes.

Impact of diagnosis of diabetes on health-related quality of life among high risk individuals: the Diabetes Prevention Program outcomes study.

PURPOSE: The purpose of this study is to assess if diagnosis of type 2 diabetes affected health-related quality of life (HRQoL) among participants in the Diabetes Prevention Program/Diabetes Prevention Program Outcome Study and changes with treatment or diabetes duration. METHODS: 3,210 participants with pre-diabetes were randomized to metformin (MET), intensive lifestyle intervention (ILS), or placebo (PLB). HRQoL was assessed using the SF-36 including: (1) 8 SF-36 subscales; (2) the physical component (PCS) and mental component summary (MCS) scores; and (3) the SF-6D. The sample was categorized by diabetes free versus diagnosed. For diagnosed subgroup, mean scores in the diabetes-free period, at 6 months, 2, 4 and 6 years post-diagnosis, were compared. RESULTS: PCS and SF-6D scores declined in all participants in all treatment arms (P < .001). MCS scores did not change significantly in any treatment arm regardless of diagnosis. ILS participants reported a greater decrease in PCS scores at 6 months post-diagnosis (P < .001) and a more rapid decline immediately post-diagnosis in SF-6D scores (P = .003) than the MET or PLB arms. ILS participants reported a significant decrease in the social functioning subscale at 6 months (P < .001) and two years (P < .001) post-diagnosis. CONCLUSIONS: Participants reported a decline in measures of overall health state (SF-6D) and overall physical HRQoL, whether or not they were diagnosed with diabetes during the study. There was no change in overall mental HRQoL. Participants in the ILS arm with diabetes reported a more significant decline in some HRQoL measures than those in the MET and PLB arms that developed diabetes.

Prevalence of pain and association with quality of life, depression and glycaemic control in patients with diabetes.

AIMS: To determine the prevalence of pain and its association with glycaemic control, mental health and physical functioning in patients with diabetes. METHODS: Cross-sectional data from a multi-site, prospective cohort study of 11 689 participants with diabetes. We analysed the associations of pain severity and interference with glycated haemoglobin (HbA(1c)) measurements and Medical Outcomes Study SF-Mental and Physical Component Summary-12 (MCS-12 and PCS-12) scores. RESULTS: Of participants, 57.8% reported moderate to extreme pain and, compared with those without pain, were somewhat older (60.8 vs. 59.9 years, P < 0.001), more obese (body mass index of 32.1 vs. 29.8 kg/m(2), P < 0.001), more likely to report being depressed or anxious (41.3 vs. 16.2%, P < 0.001) and more likely to report fair or poor health (48.5 vs. 23.1%, P < 0.001). Bivariate comparisons demonstrated that patients with extreme pain had higher HbA(1c) than those without pain (8.3 vs. 8.0%, P = 0.001). In multivariable analyses, pain was not associated with HbA(1c) (P = 0.304) but was strongly associated with worse MCS-12 (P < 0.001), PCS-12 (P < 0.001) and depression (P < 0.001). Depression was 1.3 (95% CI: 1.12, 1.96) times more likely in patients with moderate pain and 2.0 (95% CI: 1.56, 2.46) times more likely in patients with extreme pain. CONCLUSIONS: Moderate to extreme pain was present in 57.8% of diabetic patients. Pain was strongly associated with poorer mental health and physical functioning, but not worse glycaemic control. Recognizing the high prevalence of pain and its strong association with poorer health-related quality of life may be important to improve the comprehensive management of diabetes.

Methotrexate-induced myelopathy responsive to substitution of multiple folate metabolites.

Methotrexate (MTX)-associated myelopathy is a rare but serious subacute complication of MTX-based chemotherapy. We report the case of a woman with breast cancer and meningeal carcinomatosis who developed severe progressive myelopathy after four cycles of intrathecal MTX administration. We substituted high doses of the key metabolites of the methyl-transfer pathway: S-adenosylmethionine (SAM), 200 mg three times daily i.v.; folinate, 20 mg four times daily i.v.; cyanocobalamin, 100 microg once daily i.v.; and methionine, 5 g daily p.o. The patient's paraparesis improved rapidly thereafter, and magnetic resonance (MR) imaging showed resolution of the intramedullary lesions. Genetic analyses revealed homozygosity for the A allele of methylenetetrahydrofolate reductase (MTHFR) c.1298A>C (p.E429A), whereas other genetic variants of folate/methionine metabolism associated with MTX neurotoxicity were not present. Substitution with multiple folate metabolites may be a promising strategy for the treatment of MTX-induced neurotoxicity.

Target setting in intensive insulin management is associated with metabolic control: the Hvidoere childhood diabetes study group centre differences study 2005.

OBJECTIVE: To evaluate glycaemic targets set by diabetes teams, their perception by adolescents and parents, and their influence on metabolic control. METHODS: Clinical data and questionnaires were completed by adolescents, parents/carers and diabetes teams in 21 international centres. HbA1c was measured centrally. RESULTS: A total of 2062 adolescents completed questionnaires (age 14.4 +/- 2.3 yr; diabetes duration 6.1 +/- 3.5 yr). Mean HbA 1c = 8.2 +/- 1.4% with significant differences between centres (F = 12.3; p < 0.001) range from 7.4 to 9.1%. There was a significant correlation between parent (r = 0.20) and adolescent (r = 0.21) reports of their perceived ideal HbA1c and their actual HbA1c result (p < 0.001), and a stronger association between parents' (r = 0.39) and adolescents' (r = 0.4) reports of the HbA1c they would be happy with and their actual HbA1c result. There were significant differences between centres on parent and adolescent reports of ideal and happy with HbA1c (8.1 < F > 17.4;p < 0.001). A lower target HbA1c and greater consistency between members of teams within centres were associated with lower centre HbA1c (F = 16.0; df = 15; p < 0.001). CONCLUSIONS: Clear and consistent setting of glycaemic targets by diabetes teams is strongly associated with HbA1c outcome in adolescents. Target setting appears to play a significant role in explaining the differences in metabolic outcomes between centres.

Mitochondrial DNA analysis reveals Plio-Pleistocene diversification within the chacma baboon.

Modern baboons evolved as a distinct lineage prior to 2.5 Mya. Previous scenarios of diversification within this lineage have assessed the phylogenetic position of the chacma baboon of southern Africa relative to other baboons, but have not examined variation within this taxon. Here we provide a phylogenetic analysis of lineage diversity across the range of the chacma baboon, and show that: (1) chacma baboons diverged as a separate lineage at approximately 1.84 Mya; (2) the chacma lineage is characterised by a deep lineage split dividing chacmas into northeastern (1.52 Mya) and southwestern (1.22 Mya) clades; (3) ruacana baboons of Namibia form their own distinct monophyletic group within the southwestern clade, emerging approximately 0.68 Mya. These patterns likely result from a complex interplay of genetic drift and gene flow as the chacma lineage diversified across a broad geographic landscape during the climatically variable Plio-Pleistocene.

Physicians' participatory decision-making and quality of diabetes care processes and outcomes: results from the triad study.

OBJECTIVES: In participatory decision-making (PDM), physicians actively engage patients in treatment and other care decisions. Patients who report that their physicians engage in PDM have better disease self-management and health outcomes. We examined whether physicians' diabetes-specific treatment PDM preferences as well as their self-reported practices are associated with the quality of diabetes care their patients receive. METHODS: 2003 cross-sectional survey and medical record review of a random sample of diabetes patients (n=4198) in 10 US health plans across the country and their physicians (n=1217). We characterized physicians' diabetes care PDM preferences and practices as 'no patient involvement,' 'physician-dominant,' 'shared,' or 'patient-dominant' and conducted multivariate analyses examining their effects on the following: (1) three diabetes care processes (annual hemoglobin A1c test; lipid test; and dilated retinal exam); (2) patients'satisfaction with physician communication; and (3) whether patients' A1c, systolic blood pressure (SBP), and low-density lipoprotein cholesterol (LDL) were in control. RESULTS: Most physicians preferred 'shared' PDM (58%) rather than 'no patient involvement' (9%), 'physician-dominant' (28%) or 'patient dominant' PDM (5%). However, most reported practicing 'physician-dominant' PDM (43%) with most of their patients, rather than 'no patient involvement' (13%), 'shared' (37%) or 'patient-dominant' PDM (7%). After adjusting for patient and physician-level characteristics and clustering by health plan, patients of physicians who preferred 'shared' PDM were more likely to receive A1c tests [90% vs. 82%, AOR: 2.05, 95% CI: 1.03-3.07] and patients of physicians who preferred 'patient-dominant' treatment decision-making were more likely to receive lipid tests [60% vs. 50%, AOR: 1.58, 95% CI: 1.04-2.39] than those of providers who preferred 'no patient involvement' in treatment decision-making. There were no differences in patients' satisfaction with their doctor's communication or control of A1c, SBP or LDL depending on their physicians' PDM preferences. Physicians' self-reported PDM practices were not associated with any of the examined aspects of diabetes care in multivariate analyses. CONCLUSIONS: Patients whose physicians prefer more patient involvement in decision-making are more likely than patients whose physicians prefer more physician-directed styles to receive some recommended risk factor screening tests, an important first step toward improved diabetes outcomes. Involving patients in treatment decision-making alone, however, appears not to be sufficient to improve biomedical outcomes.

Interobserver reproducibility of Gleason grading: evaluation using prostate cancer tissue microarrays.

OBJECTIVES: Due to PSA screening and increased awareness, prostate cancer (PCa) is identified earlier resulting in smaller diagnostic samples on prostate needle biopsy. Because Gleason grading plays a critical role in treatment planning, we undertook a controlled study to evaluate interobserver variability among German pathologists to grade small PCas using a series of tissue microarray (TMA) images. METHODS: We have previously demonstrated excellent agreement in Gleason grading using TMAs among expert genitourinary pathologists. In the current study, we identified 331 TMA images (95% PCa and 5% benign) to be evaluated by an expert PCa pathologist and subsequently by practicing pathologists throughout Germany. The images were presented using the Bacus Webslide Browser on a CD-ROM. Evaluations were kept anonymous and participant's scoring was compared to the expert's results. RESULTS: A total of 29 German pathologists analysed an average of 278 images. Mean percentage of TMA images which had been assigned the same Gleason score (GS) as done by the expert was 45.7%. GSs differed by no more than one point (+/-1) in 83.5% of the TMA samples evaluated. The respondents were able to correctly assign a GS into clinically relevant categories (i.e. <7, 7, >7) in 68.3% of cases. A total of 75.9% respondents under-graded the TMA images. Gleason grading agreement with the expert reviewer correlated with the number of biopsies evaluated by the pathologist per week. Years of diagnostic experience, self-description as a urologic pathologist or affiliation with a university hospital did not correlate with the pathologist's performance. CONCLUSION: The vast majority of participants under-graded the small tumors. Clinically relevant GS categories were correctly assigned in 68% of cases. This raises a potentially significant problem for pathologists, who have not had as much experience evaluating small PCas.

Are family factors universally related to metabolic outcomes in adolescents with Type 1 diabetes?

AIMS: To assess the importance of family factors in determining metabolic outcomes in adolescents with Type 1 diabetes in 19 countries. METHODS: Adolescents with Type 1 diabetes aged 11-18 years, from 21 paediatric diabetes care centres, in 19 countries, and their parents were invited to participate. Questionnaires were administered recording demographic data, details of insulin regimens, severe hypoglycaemic events and number of episodes of diabetic ketoacidosis. Adolescents completed the parental involvement scale from the Diabetes Quality of Life for Youth--Short Form (DQOLY-SF) and the Diabetes Family Responsibility Questionnaire (DFRQ). Parents completed the DFRQ and a Parental Burden of Diabetes score. Glycated haemoglobin (HbA(1c)) was analysed centrally on capillary blood. RESULTS: A total of 2062 adolescents completed a questionnaire, with 2036 providing a blood sample; 1994 parents also completed a questionnaire. Family demographic factors that were associated with metabolic outcomes included: parents living together (t = 4.1; P < 0.001), paternal employment status (F = 7.2; d.f. = 3; P < 0.001), parents perceived to be over-involved in diabetes care (r = 0.11; P < 0.001) and adolescent-parent disagreement on responsibility for diabetes care practices (F = 8.46; d.f. = 2; P < 0.001). Although these factors differed between centres, they did not account for centre differences in metabolic outcomes, but were stronger predictors of metabolic control than age, gender or insulin treatment regimen. CONCLUSIONS: Family factors, particularly dynamic and communication factors such as parental over-involvement and adolescent-parent concordance on responsibility for diabetes care appear be important determinants of metabolic outcomes in adolescents with diabetes. However, family dynamic factors do not account for the substantial differences in metabolic outcomes between centres.

Cerebrovascular response time to a breath-holding challenge.

BACKGROUND: To evaluate the timecourse of cerebrovascular reserve response to breath-holding. PATIENTS AND METHODS: Using simultaneous bilateral transcranial Doppler (TCD) recordings from the MCA during a breath-holding challenge, we measured the time interval between baseline and peak blood flow velocity values in 25 patients with critical unilateral internal carotid artery (ICA) stenosis (> 85% lumen diameter reduction), in 9 patients with a non-critical (70-85%) ICA-stenosis and in 27 normal controls. RESULTS: Normal controls and patients with non-critical stenosis reached peak MCA velocities on both sides almost simultaneously. For the patients with critical stenosis the peak response time ipsilateral to the stenosis was delayed 2.40 +/- 3.43 sec compared to the opposite side. This delay resolved after carotid endarterectomy. CONCLUSIONS: In response to a breath-holding challenge unilateral critical ICA stenosis is associated with a significant ipsilateral prolongation of the rise time from baseline to peak MCA velocity.

Nitric oxide-mediated inhibition of androgen receptor activity: possible implications for prostate cancer progression.

Chronic inflammation increases the risk of cancer and many cancers, including prostate cancer, arise at sites of chronic inflammation. Inducible nitric oxide synthase (iNOS) is an enzyme dominantly expressed during inflammatory reactions. Although synthesis of high amounts of nitric oxide (NO) by iNOS has been demonstrated in pathophysiological processes, such as acute or chronic inflammation, autoimmune diseases or tumorigenesis, the role of iNOS activity in most of these diseases is poorly understood. Analysing prostate cancer biopsies by immunohistochemistry we found iNOS protein expression in tumor cells strongly paralleled by nitrotyrosine suggesting that iNOS is fully active. In vitro, NO inhibits androgen receptor-dependent promoter activity and prostate specific antigen production as well as DNA-binding activity of the androgen receptor (AR) in a concentration-dependent manner. Inhibition of the activity of androgen receptor-dependent reporter constructs is neither owing to diminished AR protein levels nor owing to an inhibition of its nuclear import. In addition, NO inhibits the proliferation of androgen receptor-positive prostate cancer cells significantly more efficiently than proliferation of androgen receptor-negative prostate cancer cells. In summary, our findings suggest that intratumoral iNOS activity favors development of prostate cancer cells that are able to proliferate androgen receptor-independently, thereby promoting prostate tumor progression.

Predictors for long-term survival after interdisciplinary salvage surgery for advanced or recurrent gynecologic cancers.

BACKGROUND AND OBJECTIVES: We wanted to identify factors which allow predicting long-term survival after pelvic exenteration (PE) for locally advanced or recurrent gynecologic malignancies. METHODS: All patients undergoing PE at our institution from 1983 to 2002 were screened. In 203 cases data were obtainable and analyzed with respect to factors predicting outcome considering morbidity, mortality, and survival. Follow-up data and data concerning late complications not documented in our records were obtained by telephone interviews. RESULTS: Mean age was 55 (22-77) years. PE was performed for locally advanced (36%) or recurrent (64%) cervical (n = 133), endometrial (n = 26), vaginal (n = 23), vulvar (n = 10), and ovarian cancer (n = 11, cases with rectum and/or bladder resections). In 13.4% (n = 26) the intent of the procedure was palliation in the remaining cure. Procedures performed were anterior (n = 91), posterior (45), or total (n = 67) PE. 53% of patients underwent preoperative radio-chemotherapy, 11.8% as a neoadjuvant treatment. Mean OR time was 8.1 hr, an average of 5.6 units of packed red blood cells were perioperatively transfused. Microscopically complete resection was achievable in n = 69 patients. Perioperative mortality was 1% (n = 2). Seventy-one percent (n = 144) of patients were available for follow-up. Five-year overall survival in patients treated with a curative intent was 21%, 5-year survival in those patients with complete resection was 32%. Forty-two percent of patients with a complete resection without lymph node involvement, age 30-50, curative intention, and the absence of a pelvic sidewall infiltration survived 5 years or longer. CONCLUSION: In our series a 5-year survival rate of over 40% could be achieved for nodal-negative patients without pelvic sidewall infiltration when treated with curative intent and after complete resection.

Inferring Plio-Pleistocene southern African biochronology from facial affinities in Parapapio and other fossil papionins.

Buried in the same South African cave deposits as Australopithecus, fossil papionins have been referred to Parapapio (Pp. whitei, Pp. broomi, Pp. jonesi, Pp. antiquus), Papio (P. izodi, P. angusticeps, P. h. robinsoni), Theropithecus (e.g., T. darti), Gorgopithecus, or Dinopithecus on the basis of postcanine tooth size and descriptive morphology of the muzzle. The morphological patterns of variation that these papionins demonstrate can help to place the Australopithecus fossils into a biochronological context and provide valuable information for reconstructing regional Plio-Pleistocene turnover. To document these patterns of variation across fossil-bearing sites, we explore morphometric affinities within Parapapio, and between Parapapio and other Plio-Pleistocene taxa (Dinopithecus ingens, Papio angusticeps, Papio izodi, and Theropithecus darti) by analyzing a sample of interlandmark distances derived from 3-D coordinate data of the most complete fossil papionin specimens available. Bivariate and multivariate analyses show that Pp. whitei exhibits as much variation between sites and between individuals as Pp. broomi and Pp. whitei combined. Diversity in Parapapio at Makapansgat and Sterkfontein may suggest substantial time depth to the caves. Theropithecus darti, Dinopithecus ingens, Papio angusticeps, Pp. whitei from Bolt's Farm (BF 43), and Pp. jonesi from Sterkfontein (STS 565) differ considerably from one another. Other Parapapio specimens across sites form a separate cluster with P. izodi from Taung, suggesting a Pliocene age for this site.

The necessity of functional proteomics: protein species and molecular function elucidation exemplified by in vivo alpha A crystallin N-terminal truncation.

Ten years after the establishment of the term proteome, the science surrounding it has yet to fulfill its potential. While a host of technologies have generated lists of protein names, there are only a few reported studies that have examined the individual proteins at the covalent chemical level defined as protein species in 1997 and their function. In the current study, we demonstrate that this is possible with two-dimensional gel electrophoresis (2-DE) and mass spectrometry by presenting clear evidence of in vivo N-terminal alpha A crystallin truncation and relating this newly detected protein species to alpha crystallin activity regulation by protease cleavage in the healthy young murine lens. We assess the present state of technology and suggest a shift in resources and paradigm for the routine attainment of the protein species level in proteomics.

[Future of chemotherapy]. / Zukunft der Chemotherapie.

The future development of chemotherapy is derived based upon recent advances. With regard to adjuvant therapy a trend towards standardized prediction of recurrence risk using all available prognostic markers (e.g., nomograms) is observed. Furthermore, in some tumors major progress has been made regarding the development of "molecular classifiers" defining tumor biology (predicting clinical outcome) by analysis of molecular changes. In adjuvant therapy considerable advances may be achieved by use of new chemotherapeutic agents as well as sequential, dose-dense and dose-intensified regimens. However, in metastatic disease no breakthrough can be expected at least with regard to survival suggesting that quality of life needs to be addressed with more emphasis. Using targeted drugs alone or in combination with chemotherapy advances concerning adjuvant therapy as well as metastatic disease are observed. Further targeted drugs have entered clinical development. However, clarification of the relation between detection of the target(s) and drug activity will fundamentally change current treatment concepts.

Laser filaments generated and transmitted in highly turbulent air.

The initiation and propagation of a filament generated by ultrashort laser pulses in turbulent air is investigated experimentally. A filament can be generated and propagated even after the beam has propagated through strongly turbulent regions, with structure parameters C(n)2 as many as 5 orders of magnitude larger than those encountered in the usual atmospheric conditions. Moreover, the filament's position within the beam is not affected by the interaction with a turbulent region. This remarkable stability is allowed by the strong Kerr refractive-index gradients generated within the filament, which exceed the turbulence-induced refractive-index gradients by 2 orders of magnitude.