Macro- and mesoscale pattern interdependencies in complex networks.

Identifying and explaining the structure of complex networks at different scales has become an important problem across disciplines. At the mesoscale, modular architecture has attracted most of the attention. At the macroscale, other arrangements-e.g. nestedness or core-periphery-have been studied in parallel, but to a much lesser extent. However, empirical evidence increasingly suggests that characterizing a network with a unique pattern typology may be too simplistic, since a system can integrate properties from distinct organizations at different scales. Here, we explore the relationship between some of these different organizational patterns: two at the mesoscale (modularity and in-block nestedness); and one at the macroscale (nestedness). We show experimentally and analytically that nestedness imposes bounds to modularity, with exact analytical results in idealized scenarios. Specifically, we show that nestedness and modularity are interdependent. Furthermore, we analytically evidence that in-block nestedness provides a natural combination between nested and modular networks, taking structural properties of both. Far from a mere theoretical exercise, understanding the boundaries that discriminate each architecture is fundamental, to the extent that modularity and nestedness are known to place heavy dynamical effects on processes, such as species abundances and stability in ecology.

Use of neutral protamine lispro insulin (NPL) in patients with hyperglycemia receiving parenteral nutrition.

AIMS: Nutritional support with parenteral nutrition (PN), a key component in the care of critically ill patients, usually requires insulin therapy in patients with diabetes or may require insulin treatment in patients not known to be diabetic. We wanted verify whether it is possible to use neutral protamine lispro (NPL) in double administration monotherapy in patients receiving artificial nutrition (AN) and if the same NPL is capable of obtaining and maintaining acceptable glycemic control without inducing hypoglycemia. PATIENTS AND METHODS: We studied 18 consecutive patients, who were not taking insulin, they needed to start artificial nutrition, and presenting at least two consecutive blood glucose > 120 mg/dL. Each patient was given at least 1 U of insulin for every 10 grams of glucose infused. RESULTS: Eighteen consecutive patients, not stratified in any way, were judged eligible in the last 24 months, with a mean age of 71 years (range 54-85 yrs). All patients were evaluated after 2, 3 and 5 days of treatment; only 1 patient has not been evaluated to 5 days. Mean glycemic values on days 2, 3, 5 were in range between 145 and 180 mg/dL. Any adjustments in NPL dose were carried out by the team of nutrition and there was no hypoglycemia that required medical intervention in emergency. CONCLUSIONS: Our impression is that also lispro protamine insulin (NPL) in double subcutaneous administration may contribute to improving the glycemic values in patients receiving parenteral nutrition with hyperglycemia.

Insulin glargine in patients with severe hepato-gastroenterology diseases and hyperglycemia receiving parenteral nutrition.

OBJECTIVE: The aim of this nonrandomized observational study is to verify and confirm whether it is possible to use insulin glargine (Lantus) subcutaneously in patients receiving parenteral nutrition (PN) and whether the analogue is capable of obtaining and maintaining good glycemic control without inducing hypoglycemia. MATERIALS AND METHODS: The sample is made up of 25 patients with severe hepato-gastroenterology diseases receiving parenteral nutrition, diagnosed diabetics and non-diabetics, who had previously been prescribed traditional insulin therapy. All were to be given subcutaneous insulin glargine at a dosage equal to the average of insulin/day administered in the preceding days spent receiving PN. RESULTS: Twenty-five consecutive patients, not stratified in any way, were judged eligible in the last six months of 2004 and first eight months of 2005. Four out of these 25 cannot be evaluated, either because (2/4) they did not begin or complete the treatment with Lantus or because the proper number of glycemic tests were not done (2/4); 21/25 patients, 84% of the sample with a mean age of 65.9 years (range 46-93 yr), finished the study and can be evaluated. The mean glycemic values after treatment with glargine were already better on the second day, and on the seventh day the difference was statistically significant. No hypoglycemias occurred which required medical intervention. CONCLUSIONS: This study confirms the possibility of using insulin glargine in patients receiving parenteral nutrition with hyperglycemia diagnosed diabetics or not diabetics.

Use of insulin glargine in patients with hyperglycaemia receiving artificial nutrition.

The purpose of this study was to verify whether it is possible to use insulin glargine (Lantus) subcutaneously in patients receiving artificial nutrition (AN) and if the analogue is capable of obtaining and maintaining good glycaemic control without inducing hypoglycaemia. The sample considers 25 patients receiving AN, diagnosed diabetics and non-diabetics, who had previously been prescribed traditional insulin therapy. All were to be given subcutaneous insulin glargine at a dosage equal to the average of insulin/day administered in the preceding days spent receiving AN. Twenty-five consecutive patients, not stratified in any way, were judged eligible in the last six months of 2004 and first two months of 2005. Four out of these 25 could not be evaluated, either because they did not begin or complete the treatment with Lantus (3/4) or because the proper number of glycaemic tests were not carried out (1/4); 21/25 patients, 84% of the sample with a mean age of 68.7 years (range 46-91 years), finished the study and could be evaluated. The mean glycaemic values after treatment with glargine were already better on the second day, and on the seventh day the difference was statistically significant. No hypoglycaemia requiring medical intervention occurred. This study confirms the possibility of using insulin glargine in patients receiving AN with hyperglycaemia regardless of the type of nutrition and whether or not the patient is diabetic.

[Promoting physical activity in overweight and obese patients: counseling in primary care from Italy (Cesena, 2002--2003)]. / La promozione dell'attività fisica nel paziente in sovrappeso ed obeso nelle Cure Primarie: un'esperienza di counseling condotta nell'Azienda Sanitaria di Cesena (2002--2003).

Lack of physical activity and obesity represent important public health problems. The objectives of the current study is to evaluate the effects of a counseling intervention (the PACE protocol) conducted by general practitioners and designed to motivate persons who are overweight or obese to increase their levels of physical activity. The counseling was offered 145 patients with a BMI > or =27 who were seen between May 2002 and April 2003 in the offices of 10 general practioners. The intervention, which lasted 3-5 minutes, was conducted during routine visits, based on the Prochaska-DiClemente model of behavioral change. Changes in the motivation of the patients to engage in physical activity and actual changes in levels of activity were measured, as were BMI and abdominal circumference. The median followup was 9 months. Among the 145 eligible patients, 103 (71%) agreed to particpate. Six months following the counselling, there was a significant change in both the motivational status and physical activity of the group, and they experienced significant decreases in BMI and abdominal circumference. Counseling using the PACE model appears to positively influence levels motivation and of physical activity in those patients who agreed to participate. Further studies should be conducted to evaluate the effectiveness of this strategy in other settings and the public health benefits of such counseling.

Detection of oncogenic human papillomavirus in sporadic retinoblastoma.

PURPOSE: To investigate the presence of human papillomavirus (HPV) DNA in tumour tissue from patients with unilateral retinoblastoma. METHODS: Samples of paraffin-embedded tumour tissue from 43 children with unilateral retinoblastoma were collected to investigate the presence of HPV DNA using polymerase chain reaction (PCR) and dot blot hybridization. RESULTS: Oncogenic HPV DNA types 16 and 35 were detected in 12 (27.9%) of 43 tumour specimens. A higher frequency of differentiated tumours (63.3%) was observed among the HPV-positive tumours. CONCLUSIONS: Future studies are necessary to demonstrate an association between HPV and sporadic retinoblastoma.

Detection of human papillomavirus in epithelial lesions of the conjunctiva.

CONTEXT: Many factors like exposure to UV radiation, climatic conditions, genetic predisposition, immunological state and, more recently, the presence of HPV have been implicated in the genesis of some lesions of the conjunctiva, especially the carcinoma. OBJECTIVE: To evaluate the presence of HPV DNA in acquired lesions of the conjunctiva and in normal mucosa. TYPE OF STUDY: Cross-sectional study. SETTING: A public university referral center (the Ophthalmology Service of the A.C. Camargo Hospital - A. Prudente Foundation, São Paulo). PARTICIPANTS: Thirty patients with acquired lesions of the conjunctiva and 60 matched controls (by age and sex) were evaluated in this study, from June 1993 to March 1995. PROCEDURES: The detection of HPV DNA in the normal conjunctiva and in acquired lesions was done by the PCR technique and dot blot hybridization. The material was collected by scraping the normal mucosa and the surface of the lesions. A fragment of fresh frozen tissue and paraffin embedded specimens of each lesion were also included. MAIN MEASUREMENTS: The association between the HPV infection and the presence or absence of conjunctival lesions. RESULTS: Sequences of HPV DNA were detected in 4 of the 31 lesions evaluated (12.9%) and in the healthy mucosa of one individual of the control group (1.6%). HPV type 16 was detected in 2 carcinomas and in the normal mucosa of one individual of the control group. HPV type 11 was demonstrated in 2 papillomas of one patient with lesions in both eyes. CONCLUSIONS: The low frequency of HPV DNA found in the lesions of this sample and the detection of the viral genome in the normal mucosa indicate that there is a weak possibility of association between HPV infection and the carcinoma of the conjunctiva.

Radiotherapy and concurrent continuous infusion of cisplatin with adjuvant surgery in nonresectable Stage III lung carcinoma: short- and long-term results of a Phase II study.

PURPOSE: Cisplatin-enhanced radiotherapy plus adjuvant surgery was evaluated in nonresectable non-small cell lung carcinoma (NSCLC). METHODS AND MATERIALS: Doses of 50 Gy (administered in standard fractionation in 5 weeks) were delivered with concurrent cisplatin in continuous infusion (daily dose: 4 mg/m2), to 32 Stage IIIa and 45 Stage IIIb patients enrolled in a Phase II study. Patients without progression underwent surgery. RESULTS: Esophagitis (64%), nausea/vomiting (34%), and pulmonary toxicity (14%) were the main side effects. Grade 3 toxicity occurred in 4 instances. A clinical locoregional major response was achieved by 55 patients (there were 10 complete responses). Forty patients underwent surgery, 7 with a nonradical procedure. Seven patients died due to surgery-related complications, which were significantly impacted by right pneumonectomy (71% vs. 6% of the other procedures, p < 0.0001). Eighteen of the 40 surgical patients were assessed to be without viable tumor and 11 with microresidual carcinoma. There were 13 disease-free, 5-year survivors. CONCLUSIONS: Toxicity was low but activity high with the chemoradiotherapy. Adjuvant surgery increased the rate of complete responses, but right pneumonectomy had an unacceptable mortality. The role of surgery needs further refinement. Integration of the chemoradiotherapy schedule with cisplatin-based induction chemotherapy is advisable.

Treatment planning for radiotherapy in northern Italy: a survey by the National AIFB-AIRO Committee on 3D-Treatment Planning. Italian Association for Biomedical Physics. Italian Association for Radiation Oncology.

BACKGROUND AND PURPOSE: A survey was performed in 1996 to investigate the structures and the process of radiation therapy treatment planning in clinical practice within northern Italy, with particular emphasis on the current and future implementation of 3D equipment and techniques. MATERIALS AND METHODS: Of 57 existing radiation therapy (RT) centres covering a population of 25 million people (45% of the total population of Italy) and treating over 58,000 cancer patients (70% of the cancer cases in Italy) each year, 46 centres were deemed eligible for the survey; a questionnaire was sent to a medical physicist working in each eligible RT centre, 40 of whom responded, making the basis for this report. RESULTS: A dedicated CT scanner was available in 25% of the responding centres and a total of 49 radiation therapy planning systems (RTPS) were reported; none of the RTPS were able to perform 3D calculations, but 50% of the centres had an advanced 2D or 2.5D system. Connection between CT scan and RTPS was by tape or disk in 62% of centres. Immobilization devices were used frequently for head and neck patients (88% of centres), but not for lung (16%) or prostate cancer (24%) patients; the number of contoured slices was largely variable, exceeding 10 in only about 30% of the responding centres. The average working time per patient seemed to closely reflect the number of slices used and the number of critical organs contoured. Finally, the majority of the responding physicists did not favour the use of more than 20 CT slices for 3D treatment planning, nor did they forecast a general spread of this technique in the next 2-3 years. CONCLUSIONS: This survey has shown (1) a heterogeneous picture, with 20% of centres ready to implement 3D techniques and 20% of centres lacking the possibility of planning treatments and (2) a general difficulty in coping with the workload represented by 3D treatment planning.

Altered fractionation radiotherapy in lung cancer.

Clinical trials on altered fractionation radiotherapy (RT) regimens currently play a significant role in lung cancer, due to the importance of local control and to the disappointing therapeutic results in this disease. In non-small-cell lung cancer (NSCLC) two strategies are being actively investigated: hyperfractionation with a "curative" aim, and hypofractionation with a palliative aim; in small-cell lung cancer (SCLC) altered fractionation seems to play a minor role at this moment. In this review paper the results of reported randomised trials are summarised and discussed. Conclusions may indicate that through hyperfractionation, particularly if accelerated, clinical outcome of non-metastatic NSCLC patients can be improved; data are however not sufficiently mature to advise its use outside controlled clinical trials. In the palliative setting, hypofractionation should be considered standard treatment.

The role of radiotherapy in the treatment of carcinoma of the prostate: a survey of clinical practices in Lombardy, Italy, by the AIRO-Lombardia Cooperative Group. Italian Association for Radiation Oncology.

AIMS AND BACKGROUND: We report the results of a survey performed in 1994 by the AIRO-Lombardia Cooperative Group, on the clinical patterns of radiation treatment for prostatic carcinoma in Lombardy, Italy, involving all radiotherapy centers serving an overall local population of about 8,800,000 people. METHODS: A questionnaire was sent to all 13 radiotherapy centers throughout Lombardy, asking for demographic and treatment details concerning the local population of patients with a localized (T1-4, N0-1, M0) carcinoma of the prostate treated with radiotherapy; 12 centers responded, making the basis for the present report. RESULTS: Analysis of collected data showed that in Lombardy: a) approximately 400 patients per year are irradiated for a localized carcinoma of the prostate, accounting for less than 30% of the total expected number of patients with this disease presentation; b) a complete staging (with PSA, transrectal ultrasonography, abdomino-pelvic CT or MRI scan and total-body bone scan) is performed in over 95% of patients before initiating radiotherapy; c) significant differences exist between radiotherapy centers as regards treatment planning and delivery. CONCLUSIONS: An urgent need exists for implementing procedures aimed at standardizing radiotherapy procedures within Lombardy.

Postsurgical policy in stage I testicular seminoma: cost and benefit of prophylactic irradiation in a long-term experience.

The definitive cure rate for clinical stage 1 testicular seminoma is very close to 100%, and prophylactic irradiation of the regional lymph nodes is associated with a low morbidity. Nevertheless, in recent years a "wait-and-see" policy has been proposed by some researchers. We analysed the cost/benefit ratio of radiotherapy (RT) by review of the case histories of 299 patients treated at the Department of Radiotherapy of the Istituto Nazionale per lo Studio e la Cura dei Tumori in Milan from January 1968 to December 1989. The 5-year overall survival was 99% (97.5% at 10 years), while the 10-year disease-free survival was 96%. The recurrence rate was 2.3%, but no patient relapsed in the irradiated areas. Acute toxicity was very moderate with only 4 (1.3%) serious radiation sequelae occurring 6 to 27 years after treatment. However, 9 second malignancies (3%) were observed. Lastly, we have calculated the costs for our National Health Service comparing surveillance policy and prophylactic irradiation.

Hyperfractionated radiotherapy and concomitant cisplatin in stage III non-small cell lung cancer: a phase II study by the AIRO-Lombardia Cooperative Group.

A multicenter Phase II study was performed by the AIRO-Lombardia Cooperative Group on 36 patients with Stage III non-small cell lung cancer. The treatment schedule included hyperfractionated radiotherapy, 1.2 Gy twice daily (5 days/week) up to a total dose of 69.6 Gy, and concomitant cisplatin by continuous infusion using a portable pump, 16 mg/m2/week for 6 weeks. Overall, adequate treatment (defined as a total dose > 66 Gy in < 46 days and 6 weeks of infusional cisplatin) was received by 56% of accrued patients. Response was complete in 6% and partial in 56% of patients; median survival was 8 months and 1-year survival rate was 37%. Site of first failure was local in 43%, distant in 43%, local and distant in 10% and unknown in 3% of failing patients. Grade 3 esophagitis was recorded in 14% of patients and a fatal case of late pulmonary toxicity was reported. On the basis of feasibility, toxicity and survival results, the planned extension to Phase III was abandoned by the Group.

Hunger sensation in patients with compensated and and uncompensated type 1 and type 2 diabetes mellitus.

OBJECTIVE: Diabetic patients (DP) refer increased hunger sensation (HS) when hyperglycemic but not yet ketogenic. As HS shows a within-day (ultradian cyclicity) and intra-day (circadian cyclicity) repetitivity, its recursive pattern was investigated in patients with type 1 and type 2 diabetes mellitus (DM), in compensated and uncompensated metabolic stage. METHOD: HS was approached in its cyclic structure by means of spectral analysis (SA), and in its circadian rhythmicity by means of Single Cosinor analysis (SCA), applied to self-rated scores of HS given every 30 min to their HS (orexigram) by DP. RESULTS: Exaggerated periprandial, interprandial, and/or nocturnal peaks of HS were seen in the orexigram of both the type I and type II DP. Specific alterations in HS periodogram were detected, structurally denoting a relative prevalence of the ultradian components along with the deamplification and loss of the circadian harmonics. DISCUSSION: The increase of HS (hyperorexia) in nonketotic DM may be formally attributed to a mechanism of frequency multiplication and amplitude demodulation in the multifrequency bioperiodic structure which physiologically regulates the recursive pattern to the daily HS in human beings.

Indications, results and techniques of radiotherapy in the treatment of small-cell lung cancer.

AIMS AND BACKGROUND: To define the role of radiotherapy in the treatment of small-cell lung cancer (SCLC) on the basis of clinical data reported in the medical literature. METHODS: Published reports are critically reviewed, with particular attention to randomized trials. RESULTS: Thoracic radiotherapy has an important role in improving local control and 3-year survival in limited-stage SCLC; radiation should be delivered early in the course of the chemotherapy program, avoiding large volumes and total doses exceeding 40-50 Gy. Thoracic radiotherapy probably has no role in resected patients treated with adjuvant chemotherapy and may even be detrimental in patients with extensive SCLC. Prophylactic cranial irradiation has been shown to reduce the risk of brain relapse, but it is not associated with a consistent increase in survival or cure rate: its use in clinical practice is therefore not advised. CONCLUSIONS: Survival rates approaching 50% at 2 years are now possible in limited SCLC with the integrated effort of the surgeon, the medical oncologist and the radiation oncologist; their strict cooperation appears to be of the utmost importance in the earliest phase of treatment planning.

Melanoma de coróide: conservaçäo de olhos com placas de cobalto-60 / Choroidal melanoma: eye preservation by cobalt-60 plaque therapy

Säo apresentados os resultados de tratamento de 28 pacientes portadores de malanoma da coróide tratados por braquiterapia com placas de cobalto-60. O tamanho dos tumores variou de 2,1 a 15mm em altura e de 9,0 a 22mm no maior diâmetro basal. Para análise dos resultados os pacientes foram subdivididos em 2 grupos: grupos I, com 19 pacientes portadores de tumores de mais de 8mm em altura; e grupo II, com 9 pacientes portadores de tumores de até 8mm de altura. Os resultados quanto à conservaçäo do globo ocular foram melhores no grupo I (78,9/100) que no grupo II (33,3). Todos os olhos enucleados tiveram confirmaçäo do diagnóstico clínico por anátomo-patológico. Dois pacientes do grupo II foram a óbito. Ambos eram portadores de outros tumores malignos sistêmicos previamente ao diagnóstico do melanoma da coróide. Pode-se questionar as hipóteses de tumor metastático ocular ou de dupla patologia tumoral nesses casos. A complicaçäo ocular mais frequente foi a retinopatia da irradiaçäo (39,3/100) seguida da catarata (28,6/100)

The role of radiotherapy in the treatment of stage III non-small cell lung cancer: a survey of clinical practices in Lombardy, Italy, by the Airo*-Lombardia Cooperative Group.

AIMS AND BACKGROUND: The role of radiotherapy in the treatment of stage III non-small cell lung cancer is controversial. The aim of this survey was to investigate the use of this modality in current clinical practice in Lombardy, a highly industrialized region of northern Italy. METHODS: A questionnaire was sent to all 13 radiotherapy centers in Lombardy, covering statistical, clinical, technical and strategical aspects, and the responses were analyzed. RESULTS: A wide range of attitudes was observed among participating radiation oncologists; the percentage of cases treated with curative intent varied largely between centers (4-100%), as did the proportion of patients given to radiation only rather than combined modality treatment (5-100% vs 0-90%). CONCLUSIONS: An urgent need exists for better cooperation between all clinicians involved in lung cancer treatment, pursuing the goals of a more uniform clinical practice and a more aggressive clinical research attitude.