Assessment of the effectiveness of the EUROFORGEN NAME and Precision ID Ancestry panel markers for ancestry investigations.

The EUROFORGEN NAME panel is a regional ancestry panel designed to differentiate individuals from the Middle East, North Africa, and Europe. The first version of the panel was developed for the MassARRAY system and included 111 SNPs. Here, a custom AmpliSeq EUROFORGEN NAME panel with 102 of the original 111 loci was used to sequence 1098 individuals from 14 populations from Europe, the Middle East, North Africa, North-East Africa, and South-Central Asia. These samples were also sequenced with a global ancestry panel, the Precision ID Ancestry Panel. The GenoGeographer software was used to assign the AIM profiles to reference populations and calculate the weight of the evidence as likelihood ratios. The combination of the EUROFORGEN NAME and Precision ID Ancestry panels led to fewer ambiguous assignments, especially for individuals from the Middle East and South-Central Asia. The likelihood ratios showed that North African individuals could be separated from European and Middle Eastern individuals using the Precision ID Ancestry Panel. The separation improved with the addition of the EUROFORGEN NAME panel. The analyses also showed that the separation of Middle Eastern populations from European and South-Central Asian populations was challenging even when both panels were applied.

Application of continuous passive motion in patients with distal radius fractures: A randomized clinical trial.

The aim of this study was to know if applying continuous passive motion (CPM) in addition to routine exercises is more effective than routine exercises alone in pain reduction, range of motion (ROM) and function improvement after distal radius fractures (DRFs). In this randomized controlled trial, 21 patients with non-stabilized DRF after pin removal were randomly assigned to experimental and control groups. The experimental group received stretching exercises with CPM machine for 2×15min per session. Both groups received routine exercises for 1h, three times a week for 4 weeks. The primary outcome measure was pain evaluated on a visual analog scale (VAS), and the secondary outcome measures were disability evaluated by the patient-rated wrist/hand evaluation and ROM (goniometry) at 4, 6, and 12 weeks. Univariate analysis of covariance (ANCOVA) and a one-way repeated measure mixed model analysis of variance (ANOVA) were used for data analysis. Twenty-one participants completed the 12-week follow-up. Pain relief, ROM and functional improvement revealed that the treatment was successful in both groups. We detected no significant differences (p>0.05) between the two groups at the end of the follow-up period regarding pain, ROM, and function. Using a CPM machine had no additional effect on pain reduction, ROM and function improvement compared with routine exercises in patients with DRF.

Developing a time-domain method for simulating statistical behavior of many-emitter systems in the presence of electromagnetic field.

In this paper, one of the major shortcomings of the conventional numerical approaches is alleviated by introducing the probabilistic nature of molecular transitions into the framework of classical computational electrodynamics. The main aim is to develop a numerical method which is capable of capturing the statistical attributes caused by the interactions between a group of spontaneous as well as stimulated emitters and the surrounding electromagnetic field. The electromagnetic field is governed by classical Maxwell's equations, while energy is absorbed from and emitted to the (surrounding) field according to the transitions occurring for the emitters, which are governed by time-dependent probability functions. These probabilities are principally consistent with quantum mechanics. In order to validate the proposed method, it is applied to three different test cases: directionality of fluorescent emission in a corrugated single-hole gold nanodisk, spatial and temporal coherence of fluorescent emission in a hybrid photonic-plasmonic crystal, and stimulated emission of a core-shell SPASER (surface plasmon amplification by stimulated emission of radiation). The results are shown to be closely comparable to the experimental results reported in the literature.

Population and forensic data for three sets of forensic genetic markers in four ethnic groups from Iran: Persians, Lurs, Kurds and Azeris.

A total of 255 individuals (Persians, Lurs, Kurds and Azeris) from Iran were typed for three sets of forensic genetic markers with the NGM SElect™, DIPplex(®) and Argus X-12 kits. Statistically significant deviations (P≤0.002) from Hardy-Weinberg expectations were observed for the insertion-deletion markers HLD97 and HLD93 after Holm-Sidák correction. Statistically significant (P<0.05) levels of linkage disequilibrium were observed between markers within two of the four studied X-chromosomal linkage groups. AMOVA analyses of the three sets of markers did not show population structure when the individuals were grouped according to their ethnic group. The Iranian population grouped closely to populations living geographically near to Iran based on pairwise FST distances. The matching probabilities ranged from 1 in 3.2×10(7) males by using haplotype frequencies of four X-chromosomal haplogroups to 1 in 3.4×10(21) individuals for the 16 autosomal STRs.

Analysis of 49 autosomal SNPs in three ethnic groups from Iran: Persians, Lurs and Kurds.

A total number of 149 individuals from Iran (Persians, Lurs and Kurds) were analyzed for 49 autosomal SNPs using PCR, SBE and capillary electrophoresis. No deviation from Hardy-Weinberg expectations was observed. One SNP pair (rs1015250-rs251934) showed significant linkage disequilibrium in Kurds. However, this was most likely due to chance. High intrapopulation variability and no significant population structure were observed among the three ethnic groups from Iran. Pairwise FST values obtained from the mean numbers of pairwise differences between SNP profiles were calculated for Persians, Lurs, Kurds and eighteen other worldwide populations. For each of the three Iranian ethnic groups, the lowest FST values calculated between an Iranian and non-Iranian populations were observed between Iranians and populations in Iraq and Turkey. The three Iranian ethnic groups grouped together with other West Asian populations in the MDS plot drawn from the FST values. Statistical parameters of forensic interest calculated for the Iranian ethnic groups showed values of the same order of magnitudes as those obtained for Asians. The mean match probability calculated for the 49 SNPs ranged from 1.7x10(-18) for Kurds to 1.3x10(-19) for Persians. Despite the low level of genetic structure observed among Persians, Lurs and Kurds, a single autosomal SNP database should be used with care when extending its forensic application to other Iranian ethnic groups.

[Effort to radically cure stage III and IV esophageal carcinoma with simultaneous radiotherapy and chemotherapy in standard clinical practice]. / L'intento di cura radicale del carcinoma esofageo al III e IV stadio con radioterapia e chemioterapia concomitanti nella pratica clinica comune.

PURPOSE: Chemotherapy and concurrent irradiation, intended to cure, are presently standard treatments for non metastatic, unresectable oesophageal cancer. The results of the combined therapy are superior to those of radiotherapy alone, attaining 25-35% 2-year survival rates. However these results mainly refer to stage I and II tumours as most of the available literature has focussed on these groups. The aim of our report is to present our experience with Stage III and IV patients. MATERIAL AND METHODS: Sixty-four Stage III and IV oesophageal cancer patients were referred to our Departments from January 1, 1990 to December 31, 1996. Diagnosis was obtained through oesophagoscopy and biopsy, stage was assessed by physical examination, chest CT scan, bronchoscopy, barium X-ray examination, upper abdomen ultrasonography and bone nuclide scan. Thirty-four patients, with no signs of blood-born metastases and in satisfactory medical conditions (i.e. age not exceeding 70 years, weight loss not exceeding 10% of body weight, normal serum values of BUN and creatinine, no other severe disease), were submitted to concurrent chemo-radiotherapy. The case features were as follows: histology of squamous cell carcinoma in 32 cases, of adenocarcinoma in 2; tumour in the upper third of the oesophagus in 11 (32.5%), in the middle third in 18 (53%), in the lower third in 5 (14.5%); male/female ratio 29/5, age 48-68 years (mean 56), Karnofsky performance status of 60% or higher. On referral, 18 out of 34 (53%) had a weight loss more than 5% of body weight and 22 (64.5%) had dysphagia. Twenty-one had Stage III (61.75%) and 13 stage IV (38.25%) cancer, with metastasis limited to the supraclavicular or coeliac nodes, which could be included in the radiation volume. In all cases chemotherapy consisted of 5-Fluoruracil (administered in a continuous i.v. infusion, from day 1 to 5, with a 750-1.000 mg/n.sq daily dose) and Cisplatin (75-100 mg/n.sq on the first day, or 20 mg/n.sq for 5 consecutive daily doses, administered by i.v. bolus). Three to 5 cycles were administered, one every 21 days. Irradiation started with the first cycle of chemotherapy in 5 patients, with the second or third cycle in 29. At least two cycles of chemotherapy were administered during the course of radiation. Radiotherapy was performed with 4 to 18 MeV linear accelerator X-rays, or telecobalt, through opposite anterior and posterior treatment portals or more complex field arrangements. The doses were in the range of 44-66 Gy, with fractionation of 5x180-200 cGy weekly sessions. After treatment, periodic follow-up controls were carried out in all cases. Thorough restaging was performed only in selected cases, thus a systematic evaluation of objective responses was not possible. Data on improvement of swallowing were always available, however, and the early therapeutic results were analysed accordingly. Toxicity was recorded according to the WHO parameters. Two-year survival after conclusion of the treatment was calculated according to Kaplan and Maier. Survival was analysed (log-rank test) according to stage, Performance Status, oesophagectomy and body weight loss. RESULTS: After treatment, subjective symptomatic relief occurred in 17 of the 22 patients presenting dysphagia (77.5%). Acute toxicity (Grade III or IV WHO) of the treatment accounted for 47% of hematologic adverse effects, 40% of mucositis, 20.5% of vomiting or diarrhoea not responding to drug treatment. Treatment delays of more than one week, due to toxicity, occurred in 23.5%. Moreover, we observed 20.5% of mild cardiotoxicity and 6% of mild nephrotoxicity. No symptomatic lung fibrosis was observed. No death could be related to toxicity. Overall 2 year survival was 13%, with a median value of 10 months. Survival analysis, according to stage, showed 2 year values of 24% in Stage III and 0% in Stage IV (p=0.09). No significant difference was related to Performance Status and weight loss. Six patients showed a remarkable improvement in symptoms and general conditions after treatment, and were restaged with oesophagoscopy, thoracic CT scan and bronchoscopy, which evidenced resectable residual tumors, and they were then operated. Although histologic examination showed tumour in all the resected specimens, 2 patients survived more than two years (33.5% survival, median 14 months). Due to the small number of operated patients, no attempt was made to assess the significance of this result, in comparison with the other cases. DISCUSSION AND CONCLUSIONS: Many Stage III and IV patients, selected for an aggressive chemo-radiation approach on the grounds of satisfactory medical conditions, can obtain relief of dysphagia. Toxicity can be severe, but is rarely life-threatening. Some cases, without extrathoracic spread of the tumor can achieve long term survival (in our experience 24% 2-year survival in Stage III, in our experience which favourably compares with the results obtained by other authors). Whether surgery may improve the therapeutic results of chemo-radiotherapy in patients whose tumour has become resectable, is an issue that cannot be satisfactorily addressed on the basis of our experience, nor are the results from the available literature exhaustive to this regard.

[Combined chemo-radiotherapy in non-operable cervico-facial neoplasms. Final results of an experience with non-selected patients]. / Integrazione chemio-radioterapica nelle neoplasie cervico-facciali inoperabili. Risultati definitivi di una esperienza su pazienti non selezionati.

The management of advanced inoperable head and neck cancer is often based on a combined chemo-radiotherapy approach. No definitive conclusions on the effectiveness of this combination can be drawn from clinical trials because these neoplasms are heterogeneous and treatment schedules vary. Many scientific trials test highly toxic combinations, whereas not only good results but also low toxicity are mandatory in the current practice. We report the results obtained in 90 consecutive patients affected with inoperable head and neck cancers in stages III-IV, or relapsed after surgery. Chemotherapy consisted of a cis-platinum/bleomycin induction phase, followed by weekly administrations of cis-platinum simultaneous with conventional irradiation. The objective remission rates, achieved at the end of the induction chemotherapy and the simultaneous chemo-radiotherapy phases, were respectively 55.5% and 84.5%. The tumor disappeared in 39% of cases, by the end of the whole treatment. With the Kaplan-Meier method, 3-year overall, progression-free and relapse-free survival rates were 21.20%, 22.25% and 38.75%, respectively. The overall survival rate, calculated with the "log-rank" test according to the stage and the site of the primary tumor, exhibited no significant differences. In contrast, significant differences (p < 0.05) were demonstrated, according to treatment intent (curative radical: 26%, vs palliative: 0%) and to the achievement of an objective response at the end of induction chemotherapy--i.e., 48% 3-year survival rate, vs 7% in chemotherapy resistant cancer patients. When limiting the analysis to 72 radically irradiated patients, however, the achievement of CR after induction chemotherapy lost its prognostic value. Toxicity was not substantially higher than with conventional irradiation. Our results are in agreement with literature data on this subject which, regarding survival, fail to prove such integrated treatments as ours better than irradiation alone. In contrast, the preliminary combination of chemotherapy and irradiation is clearly better for the patients waiting to receive radiation therapy, because tumor volume and related symptoms markedly decrease after induction chemotherapy. Currently the best survival rates (about 50% at 3 years) with chemo-radiotherapy are obtained, in this kind of cancer, by combining cis-platinum and continuous-infusion 5-fluorouracil, simultaneous with irradiation. However, frequent and severe toxicity is reported. Should such a modality be adopted in the current practice, patients should be selected according to their medical conditions.

[Radiotherapy of limited pulmonary microcytoma in current clinical practice]. / La radioterapia del microcitoma polmonare "limitato" nella pratica clinica corrente.

The use of thoracic irradiation in the treatment of "limited disease" small-cell lung cancer yields better local control and survival rates than chemotherapy alone, according to meta-analysis studies of randomized clinical trials. Outside experimental studies, however, the role radiotherapy can currently play in the management of this type of cancer is difficult to assess because treatment modalities and patient selection criteria differ greatly. We report on the treatment outcome obtained in the Radiotherapy Department of the University of Siena in a series of 86 patients with small-cell lung cancer consecutively referred, January 1986 to January 1992; after a thorough staging, 46 of them were diagnosed as having a "limited disease". A "sequential" chemo-radiotherapy combination was used: irradiation was delivered after the completion of the initial drug treatment. Twenty-four patients (52.5%) achieved a complete and 22 (47.5%) a partial objective remission after chemotherapy, with acceptable early toxicity rates and severity. Twenty-eight of them received irradiation according to the following selection criteria: objective remission after chemotherapy (19 of 24 complete responders, excluding those with initial pleural effusion or worsening medical status during chemotherapy) and initial large tumor bulk (9 of 22 patients in partial remission). The overall treatment outcome rate (median survival: 18 months, 2-year survival: 28%) is in agreement with that of similar previous studies; toxicity rates are also similar (2% of treatment-related deaths). Survival analysis, according to "performance status" score, chemotherapy schedule and the achievement of complete remission with the initial drug management, exhibited significant differences only relative to the latter parameter. Many recent clinical trials suggest that combined chemo-radiotherapy could improve these results: toxicity is however reported as heavy, with this approach. Some guidelines are here considered, which could make this combination reliable also for current clinical use.

Breast-conserving treatment of early breast cancer. Results in a common clinical trial.

Results of large prospective trials, often based on selected series and optimal treatment techniques, indicate that breast conserving therapy is appropriate for most patients with early breast cancer. Questions remain regarding the therapeutic outcome in common practice. We report on a series of 206 consecutive, unselected patients treated with current radiotherapy procedures. The Kaplan-Meier evaluation showed 5- and 8-year survival rates (93%, 91%), distant disease-free survival rates (87%, 85%) and local relapse-free survival rates (90%, 88%) that were comparable to those of the conservative arms in reported randomised trials and to the data from retrospective studies reported by authoritative institutions. However, subanalysis according to prognostic factors such as menopausal status, age and axillary nodal status was of limited value, due to the small number of cases.