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Background Although children with special health care needs (CSHCN) represent a minority of the population, they go through more hospitalizations, more admissions to the Emergency Department (ED), and receive a major number of medical prescriptions, in comparison to general pediatric population. Objectives of the study were to determine the reasons for admission to the ED in Italian CSHCN, and to describe the association between patient’s demographic data, clinical history, and health services requirements. Methods Ad hoc web site was created to collect retrospective data of 3479 visits of CSHCN to the ED in 58 Italian Hospitals. Results Seventy-two percent of patients admitted to ED were affected by a previously defined medical condition. Most of the ED admissions were children with syndromic conditions (54%). 44.2% of the ED admissions were registered during the night-time and/or at the weekends. The hospitalization rate was of 45.6% among patients admitted to the ED. The most common reason for admission to the ED was the presence of respiratory symptoms (26.6%), followed by gastrointestinal problems (21.3%) and neurological disorders (18.2%). 51.4% of the access were classified as ‘urgent’, with a red/yellow triage code. Considering the type of ED, 61.9% of the visits were conducted at the Pediatric EDs (PedEDs), 33.5% at the Functional EDs (FunEDs) and 4.6% at the Dedicated EDs (DedEDs). Patients with more complex clinical presentation were more likely to be evaluated at the PedEDs. CSHCN underwent to a higher number of medical procedures at the PedEDs, more in comparison to other EDs. Children with medical devices were directed to a PedED quite exclusively when in need for medical attention. Subjects under multiple anti-epileptic drug therapy attended to PedEDs or FunEDs generally. Patients affected by metabolic diseases were more likely to look for medical attention at FunEDs. Syndromic patients mostly required medical attention at the DedEDs. Conclusions Access of CSHCN to an ED is not infrequent. For this reason, it is fundamental for pediatricians working in any kind of ED to increase their general knowledge about CHSCN and to gain expertise in the management of such patients and their related medical complexity.

The aim of this thesis was to correlate changes in the content of (i) gonadotrophin-releasing hormone (GnRH) in brain extracts, pituitary stalk and peripheral plasma, and (ii) hypothalamic corticotrophin-releasing activity (CR-activity) with the patterns of secretion of luteinizing hormone (LH), follicle stimulating hormone (FSH) and adrenocorticotrophic hormone (ACTH) from the anterior pituitary gland and corticosterone from the adrenal gland, under various physiological and experimental conditions. Most measurements were made on samples obtained from rats of the Wistar strain, but the results of some studies in the human are reported in Chapter 8. Radioimmunoassay techniques were used to measure GnRH, LH, FSH and ACTH concentrations, while a competitive protein binding method was used to determine plasma corticosterone concentrations. CR-activity was assessed using an in-vitro assay involving short-term incubation of hemipituitaries: the amount of ACTH released into the medium was measured by radioimmunoassay. The hypothalamic content of GnRH, pituitary ACTH, and pituitary and plasma LH and FSH were measured in male, female and androgenized female rats from foetal Day 15 to postnatal Day 65. CR-activity was also measured at a few times during the postnatal period. Hypothalamic GnRH was detectable as early as foetal Day 15, increased gradually until postnatal Day 2 and then steeply between Days 5 and 16, a period during which major maturational changes occur in the hypothalamo- hypophysial axis. T|he levels of GnRH were similar in both males and normal females until Day 41, after which the increase which had been occurring from Day 16 continued in the male but not the female. In female animals treated with testosterone propionate (TP) shortly after birth, the hypothalamic content of GnRH at Day 9 was significantly less than that in normal females and males of the same age. Between Days 16 - 22 levels reached those found in the normal females and males. The lower level of GnRH in the TP treated female was associated with pituitary gonadotrophin and plasma FSH levels which were lower than in the normal female until Day.3O, suggesting that TP inhibits the synthesis and release of GnRH and gonadotrophins. In the normal female, vaginal opening was associated with a marked drop in pituitary LH and FSH and hypothalamic GnRH, but in the TP-treated female vaginal opening occurred while hypothalamic GnRH and pituitary LH levels were still rising. The peak in pituitary LH and the rise in plasma LH seen on Days 3O and 41, respectively, in the normal female were each delayed by about 1O days in the TP treated female. Similarly, the peak in pituitary FSH on Day 22 in the normal female occurred on Day 3O in the TP treated female. The profile of plasma FSH concentrations in the latter resembled more closely that of the male. In all three types of animal plasma FSH dropped significantly between Days 5O and 65. This could be attributed to inhibition of FSH release but not synthesis in the male (since pituitary FSH rose markedly during this period). However, in the androgenized female pituitary FSH also fell significantly suggesting that both release and synthesis had been inhibited. The Day 15 foetal pituitary also contained ACTH, and again levels of this hormone rose steeply between Days 5 and 9. In contrast to the gonadotrophins, there was a marked divergence between the pituitary content and concentration of ACTH, content rising while concentration remained relatively steady after Day 9. There was no major difference in pituitary ACTH levels between the three types of animal throughout the study; however, around Days 16 and 50 CR-activity was higher in the males and androgenized females compared with that in the normal females. Hypothalamic CR-activity and GnRH content, and pituitary and plasma LH, FSH and ACTH were measured in adult male rats maintained under a lighting regime in which the lights were on for 14 h. Two experiments were carried out. In the first some of the animals were kept in a room, distant from the animal house, in which the lighting was reversed with respect to the external environment. In animals exposed to the reversed lighting regime, hypothalamic GnRH content and pituitary gonadotrophin concentrations were significantly lower than the values in males kept in the animal house where they were in close proximity to female rats. In the second experiment, which was carried out on animals which had all been kept in the animal house, there were no significant differences between the GnRH contents measured at 3-4 hourly intervals throughout the day. Pituitary LH and FSH contents, but not concentrations, were significantly elevated at 12.OO h. There was little difference between the experiments in CR-activity, plasma ACTH concentrations and profiles of pituitary ACTH content and concentration. As expected there was a diurnal rhythm in plasma corticosterone concentrations; the peak occurred between 15.OO - 18.OO h. The profiles of^plasma and pituitary ACTH were similar to that of plasma corticosterone. CR-activity dropped significantly between 12.OO and 16.OO h, but remained stable at the other times. Hypothalamic GnRH and pituitary and plasma LH and FSH levels were also measured in female rats which had 4-day oestrous cycles. There were no significant differences between hypothalamic GnRH content. During pro-oestrus the mean GnRH content rose to reach a high level at 18.OO h at which time plasma LH concentration had risen sharply to a level consistent with the peak of the pre-ovulatory surge. Plasma FSH concentration also rose significantly between 15.OO and 18.00 h of pro-oestrus. At metoestrus and dioestrus plasma FSH levels were lower in the morning than in the evening. Extracts of cerebral cortex from animals of either sex, both prepubertal and adult, contained no detectable GnRH. However, cortical extracts did exhibit CR-activity This may have been due to the release of substances which cross reacted with the anti-ACTH serum but which were not steroidogenic (assessed in-vivo). These results suggest that (1) there is no diurnal rhythm in hypothalamic GnRH, (2) there may be a diurnal rhythm in pituitary gonadotrophin content in the male and in plasma FSH concentration on the days of metoestrus and dioestrus in the female, (3) if a surge of GnRH does occur on the afternoon of pro-oestrus, the rate of GnRH synthesis exceeds its release, and (4) the mechanism which regulates gonadotrophin secretion in the male may be affected by factors in the environment other than the length of daylight (e.g. presence of female animals). The data also support the view that the diurnal rhythm of corticosterone secretion is under hypothalamo-hypophys ia1 control. The effects of sex steroid hormones on the responsiveness of the neural mechanism responsible for the secretion of GnRH were examined in the female rat. Responsiveness was determined on pro-oestrus by measuring the increments in content (concentration x volume/time) of immunoreactive GnRH of pituitary stalk blood produced by electrical stimulation of the medial preoptic area or median eminence. Ovariectomy on the morning of dioestrus reduced the GnRH response to preoptic stimulation while oestradiol benzoate (OB) or TP administered immediately after ovariectomy augmented the response. The facilitatory effect of TP was possibly due to its conversion'to an aromatized derivative since 5a-dihydrotestosterone monobenzoate was ineffective. Progesterone did not facilitate preoptic responsiveness and, when administered to animals ovariectomized at 12.OO h of pro-oestrus, reduced the GnRH response at 18.OO h of the same day. Stimulation of the median eminence produced a significantly greater increment in GnRH than stimulation of the preoptic area. The facilitatory action of OB on the GnRH response was less marked for median eminence compared with preoptic stimulation. The administration of ICI 46474 at 17.00 h of dioestrus did not reduce preoptic responsiveness on the morning of the next day, suggesting that this compound does not act as an 'antioestrogen 1 at the preoptic area. In a second series of experiments, blood was collected from the cut pituitary stalk of pro-oestrous rats before and during electrical stimulation of either the anterior hypothalamic area, suprachiasmatic nuclei, hippocampus or amygdala. The mean increments in GnRH content of pituitary stalk plasma produced by median eminence (data from previous series, see above) stimulation was nearly twice that obtained by preoptic stimulation (data from Fink and Jamieson, 1976). Significant increments in GnRH content were also obtained by stimulating the suprachiasmatic nuclei or anterior hypothalamic area. However, the increments produced by stimulation of the anterior hypothalamic area were considerably less than that obtained by median eminence, preoptic or suprachiasmatic stimulation. Stimulation of the hippocampus or amygdala had no appreciable effect on GnRH content. The increments in GnRH content in animals subjected to simultaneous stimulation of the hippocampus and preoptic area were similar to that obtained by preoptic stimulation alone. However, the increment was reduced when simultaneous stimulation was preceded by ventral hippocampal stimulation. Studies were also carried out on animals subjected to section of the preoptic roof immediately before implantation of electrodes in the preoptic area. Regular oestrous cycles resumed in all these animals after a mean (± S.E.M.) of 18.8 ± 2.O days (compared with 5.5 ± O.3 days in animals subjected to electrode implantation only). The increment in GnRH content produced by preoptic stimulation was similar in the roof-sectioned compared with intact animals. However, the facilitatory effect of oestrogen on the GnRH response to preoptic stimulation was significantly reduced in the roof-sectioned compared with intact animals. (The latter study was carried out on animals ovariectomized on the morning of dioestrus and immediately afterwards given a s.c. injection of either oil or OB). These results suggest that the hippocampus and amygdala do not exert an acute, direct effect on the GnRH release mechanism, but areas outside the diencephalon may play a role in mediating the facilitatory effect of oestrogen. In agreement with the findings of other workers, integrity of the dorsal afferents of the diencephalon did not appear to be essential for maintaining regular oestrous cycles. Whether the priming effect of GnRH can be elicited by electrical stimulation of the medial preoptic area, or by i.v. infusion or multiple i.v. injections of the synthetic decapeptide was also investigated. All experiments were carried out on animals anaesthetized with sodium pentobarbitone at 13.3O h. In pro-oestrous rats, the LH response to the second of two electrical stimuli, 15 min in duration and separated by 6O min, was significantly greater than the response to the first stimulus. When synthetic GnRH was infused at a constant rate for 90 min, plasma LH increased gradually for the first 45 to 60 min after which it increased markedly. This enhanced secretion of LH did not occur in rats which were infused with the same total dose of GnRH, either 15 or 75 ng/lOO g body wt, over periods of 45 min or less. When a dose of 15 ng GnRH/100 g body wt was administered in 6 divided doses by i.v. injections, each separated by 15 min, there was a marked increase in plasma LH after 75 min. The profile of the mean plasma LH concentration in rats subjected to preoptic stimulation for 9O min was similar to that in rats infused for 90 min with GnRH, but the variation in response was much greater in the stimulated rats. These results indicate that the priming effect can be elicited by endogenous as well as synthetic GnRH, and that whether GnRH reaches the pituitary at a constant rate or in a pulsatile manner, the factor is capable of increasing significantly the responsiveness of the gonadotrophs. The relevance of these findings with respect to the development of the spontaneous preovulatory LH surge is discussed. A priming effect could not be elicited by constant GnRH infusion in dioestrus rats; this supports the view that steroid hormones, especially oestradiol-17β, determine the magnitude of the effect. The LH response in male rats^ subjected to i.v. infusion of GnRH was much lower than in females. Pre-treatment with OB did not increase the response significantly, suggesting that this sex difference cannot be ascribed simply to low levels of plasma oestrogen in the male. In a second series of experiments on the priming effect, designed to simulate the spontaneous pre-ovulatory surge of gonadotrophins, adult rats which had been anaesthetized with urethane, were subjected to either electrical stimulation of the medial preoptic area or intravenous infusion of synthetic GnRH for 6-7 h between 14.OO - 21.OO h of pro-oestrus. Plasma LH concentrations increased exponentially 3O-6O min after the start of stimulation or infusion, peaks being reached after 2-4 h (depending upon the strength of the stimulus or the dose of GnRH). The concentrations then fell, but in animals infused with GnRH, levels at the end were still significantly higher than those before the beginning of the infusion. Comparison of the profiles of plasma LH concentration with the levels of immunoreactive GnRH in pituitary stalk (preoptic stimulation study) or peripheral plasma (infusion study) suggests that the rising phase of the spontaneous LH surge could be due to increased responsiveness of the anterior pituitary to elevated, but relatively constant levels of GnRH in hypophysial portal blood. However, the declining phase of the spontaneous surge is possibly the result of a fall in both GnRH output and pituitary responsiveness. For maintaining a constant level of immunoreactive GnRH in peripheral blood during long-term infusion, PBS-0.1% gel proved to be a better diluent than O.9% saline or male rat serum. At about 2OˆC the latter appears to degrade synthetic GnRH and/or affect its immunoreactivity. The studies in the human may be divided into three experiments. In the first, the concentration of immunoreactive GnRH was determined in median eminence, hypothalamic, and cerebral cortical tissue obtained at post-mortem from patients with Huntington's chorea and from non-choreic (control) subjects. Preliminary studies showed that the slope of hypothalamic extract from control and choreic subjects, both male and female, was similar to that of the synthetic GnRH which was used as standard in the radioimmunoassay. This suggests that human hypothalamic tissue contains a substance immunologically similar to that in other species such as the rat, sheep, pig and rhesus monkey. Though the concentration of GnRH was highest in the median eminence, relatively large amounts of GnRH were also found in the preoptic nuclei. The mean concentration of GnRH in median eminence of female choreics was greater than in the female controls and the male choreics and controls. Median eminence concentration was lowest in control females (age range, 39 - 88). There was little difference between the mean concentrations of GnRH in the median eminence of the two male groups, but there was an age-related drop in the median eminence GnRH concentration of the male controls. Measurement of peripheral plasma GnRH, LH and FSH during the menstrual cycle of normal women and at random times in males and females exhibiting one of several hypogonadal states, formed the basis of the second experiment. Because of the low, and in most cases undetectable quantities of GnRH measured in the peripheral circulation, it was not possible to correlate changes in release of this hormone with patterns of LH and FSH secretion, even though all of the normal women had mid-cycle peaks in gonadotrophin concentrations and the hypogonadal patients exhibited the expected plasma LH and FSH levels. Measurement of ACTH and CR-activity in various extracts of two medullary thyroid carcinomas constituted the third experiment. While extraction with a butanol-acetic acid-water mixture or 2 N acetic acid appeared to reduce immunological ACTH concentration and CR-activity, saline extracts and lyophilized portions of the tumours contained high concentrations of immunoreactive ACTH and significant CR-activity was demonstrated in-vitro. However, it was not possible to measure significant ACTH and/or CR-activity in-vivo, though it is possible that insufficient tissue was injected to elicit the expected response. Overall, these studies provide further evidence for the contention that pGlu - His - Trp - Ser - Tyr - Gly - Leu - Arg - Pro - Gly - NH2 (GnRH) may be the (or at least 'a') substance which, under physiological conditions, mediates neural control of gonadotrophin release. Studies on CR-activity revealed the problem of using an antiserum to ACTH which also cross reacts with ACTH fragments. As for the gonadotrophin aspect, investigation of the hypothalamic-pituitary-adrena1 axis would be greatly facilitated by the characterization and synthesis of a corticotrophin-releasing factor (if one, only, exists).

Optimizing a sequence of actions to attain some future goal is the general topic of control theory Stengel (1993); Fleming and Soner (1992). It views an agent as an automaton that seeks to maximize expected reward (or minimize cost) over some future time period. Two typical examples that illustrate this are motor control and foraging for food. As an example of a motor control task, consider a human throwing a spear to kill an animal. Throwing a spear requires the execution of a motor program that is such that at the moment that the spear releases the hand, it has the correct speed and direction such that it will hit the desired target. A motor program is a sequence of actions, and this sequence can be assigned a cost that consists generally of two terms: a path cost, that specifies the energy consumption to contract the muscles in order to execute the motor program; and an end cost, that specifies whether the spear will kill the animal, just hurt it, or misses it altogether. The optimal control solution is a sequence of motor commands that results in killing the animal by throwing the spear with minimal physical effort. If x denotes the state space (the positions and velocities of the muscles), the optimal control solution is a function u(x, t) that depends both on the actual state of the system at each time and also depends explicitly on time. When an animal forages for food, it explores the environment with the objective to find as much food as possible in a short time window. At each time t, the animal considers the food it expects to encounter in the period [t, t+ T ]. Unlike the motor control example, the time horizon recedes into the future with the current time and the cost consists now only of a path contribution and no end-cost. Therefore, at each time the animal faces the same task, but possibly from a different location of the animal in the environment. The optimal control solution u(x) is now timeindependent and specifies for each location in the environment x the direction u in which the animal should move. The general stochastic control problem is intractable to solve and requires an exponential amount of memory and computation time. The reason is that the state space needs to be discretized and thus becomes exponentially large in the number of dimensions. Computing the expectation values means that all states need to be visited and requires the summation of exponentially large sums. The same intractabilities are encountered in reinforcement learning.

Motor primitives or motion templates have become an important concept for both modeling human motor control as well as generating robot behaviors using imitation learning. Recent impressive results range from humanoid robot movement generation to timing models of human motions. The automatic generation of skill libraries containing multiple motion templates is an important step in robot learning. Such a skill learning system needs to cluster similar movements together and represent each resulting motion template as a generative model which is subsequently used for the execution of the behavior by a robot system. In this paper, we show how human trajectories captured as multidimensional time-series can be clustered using Bayesian mixtures of linear Gaussian state-space models based on the similarity of their dynamics. The appropriate number of templates is automatically determined by enforcing a parsimonious parametrization. As the resulting model is intractable, we introduce a novel approximation method based on variational Bayes, which is especially designed to enable the use of efficient inference algorithms. On recorded human Balero movements, this method is not only capable of finding reasonable motion templates but also yields a generative model which works well in the execution of this complex task on a simulated anthropomorphic SARCOS arm.

We describe two related models to cluster multidimensional time-series under the assumption of an underlying linear Gaussian dynamical process. In the first model, times-series are assigned to the same cluster when they show global similarity in their dynamics, while in the second model times-series are assigned to the same cluster when they show simultaneous similarity. Both models are based on Dirichlet Mixtures of Bayesian Linear Gaussian State-Space Models in order to (semi) automatically determine an appropriate number of components in the mixture, and to additionally bias the components to a parsimonious parameterization. The resulting models are formally intractable and to deal with this we describe a deterministic approximation based on a novel implementation of Variational Bayes.

Liposoluble contrast media, used in lymph nodes x-ray examination, have some specific features, when compared with idrosoluble contrast media. They rarely diffuse through the lymphatic walls, they produce an intense and homogeneous opacity of the lymph nodes and they remain in the lymph nodes for several months. For these reasons, it was thought to substitute the iodine of the liposoluble contrast medium with I131, and to use this radioactive material for therapy in primary and secondary malignant growth of lymph nodes. Since October 1961 a series of 30 patients was treated, 22 with malignant lymphomas of various type, 8 with metastases from carcinoma of the uterus or malignant melanomas of the legs. The radioactive contrast medium was injected into the feet following the technique suggested by Kinmonth. This tecnique allowed the irradiation of lymph nodes from the inguinal to the lumbo-aortic included. Favourable results were obtained: a marked and durable reduction of the diseased lymph nodes was observed in most cases. The long permanence of the contrast medium in the lymph nodes allowed to follow the size and shape of lymph nodes up to 6 months after injection. No signs of bone marrow damage were observed. The intralymphatic radiotherapy has advantages in respect of the transcutaneous radiotherapy: 1) Irradiation of the lymph nodes from inside, without damage of other tissues; 2) simultaneous irradiation of lymph nodes in different locations, giving a high dose to each lymph node, but a low total body dose; 3) Continuous irradiation; 4) Single inoculation of the radioactive material, even without hospitalization. The limitations of the method are due to the impossibility to reach all the lymph node districts and the lymph nodes completely obliterated by carcinoma metastases, which are by-passed. As these preliminary results suggest, the intralymphatic radiotherapy is best indicated in malignant lymphomas.

Three cases of malignant lymphoma involving retroperitoneal nodes, in which the clinical diagnosis could be clearly established by lymphangiography, are reported. In two cases the left retroperitoneal node chain apparently was the only site of involvement. In one case the right retroperitoneal chain showed recurrence after two years, with roentgenologic findings identical with those described for the left chain. Lymph node biopsy confirmed the roentgenologic diagnosis in the first case, and hepatic biopsy became conclusive only after lymphangiography in the third patient. In the second case it was possible by lymphangiography to detect pathologic lymph nodes in the retroperitoneal space in the absence of positive physical and other roentgenologic and laboratory findings.

A new clinical classification for Hodgkin's disease is proposed by the Committee for the Study of Malignant Lymphomas of the National Cancer Institute of Milan in cooperation with the Institute of Radiology of the University of Milan. The method of treatment of Hodgkin's disease adopted in these Institutes is also outlined. The histologic classification includes paragranuloma, nodular sclerosis, granuloma and sarcoma. Stage I: disease limited to a single peripheric lymphatic region. Within this stage two groups can be recognized: a) involvement of one single lymph node or few nodes limited to a small area of the region (unifocal lesions); b) involvement of many nodes spread throughout the region (uniregional lesions). Stage II: disease limited to two contiguous lymphatic regions, or to few deep nodes (mediastinal, retroperitoneal). Stage III: disease limited to two non contiguous peripheric lymphatic regions, or to many peripheric and/or deep (mediastinal, retroperitoneal) regions, provided the involvement is either above or below the diaphragm. Stage IV: generalized disease with involvement of lymph nodes above and below the diaphragm, or involvement of one or more lymphatic regions with concomitant involvement of visceral organs, bones, marrow, nervous system and skin. Systemic symptoms and signs, fatigue, fever, night sweats, loss of weight, itching, anemia, lymphocytopenia, high erythrosedimentation rate) must be recorded in each case to evaluate prognosis and proper treatment, bu are not considered in this classification for lymph node staging. Primary visceral, bone, nervous and cutaneous involvement is exceptional; therefore staging for such lesions is not considered in this classification. In all stages endolymphatic radiotherapy with Lipiodol F 131I is indicated (10 ml in each foot with 2.5 mc/ml, corresponding to a tumor-dose of 15 - 20,000 rads). This is considered as a radical as well as a prophylactic treatment for those lymph nodes adequally filled with the contrast material; in case of non filling or incomplete filling of part of the lymph node chain, treatment will be completed with external radiation therapy. Stage I and II are treated with radical and prophylactic radiotherapy. If systemic symptoms and signs are still present after radiotheraphy, a course with anticancer drugs will be administered. Radiation therapy is given with high voltage or Co60 units. In radical treatments tumor doses of at least 3,000 r within 3–4 weeks are administered to all involved lymphatic regions. Prophylactic radiotherapy is indicated for regions clinically free of disease but contiguous to the involved areas, with tumor doses not less than 3,000 r in 3–4 weeks. In stage II radical radiotherapy follows a course with chemotherapy. In stage IV chemotherapy is the treatment of choice; palliative radiotherapy is given to any bulk of tumors, wherever the location, when specific symptoms can be attributed to the masses. The anticancer drug of choice is methyl-bis-(β-chloro-ethyl)-amine HCl(HN2) 0.4 mg/kg i.v., for those patients who did not receive any previous course of chemotherapy. Otherwise, as well as during the course of the disease, other polyfunctional alkylating agents, vinblastine (alone or in combination with chlorambucil), methylhydrazine, and corticosteroids will be administered according to each clinical situation. Radical surgery followed by radical radiotherapy is reserved for primary lymphatic involvement only in specially selected patients in stage I with unifocal lesions. Primary involvement of the stomach, small bowel or colon is treated by surgical extirpation and radiotherapy. Splenectomy is indicated when this viscus is the only site of involvement. During pregnancy radiation therapy is not administered below the diaphragm. Chemotherapy is not given during the first 4 months of pregnancy. The need for one internationally accepted clinical classification of Hodgkin's disease is stressed.

Arteriography was carried out on 54 patients with benign and malignant tumors of soft tissues of the extremities. Results are reported and the most significant angiographic pictures of 28 cases are illustrated in detail. These include 2 neurilemmomas, 1 gigantocellular tumor (sesamoid tumor), 1 synovial gigantocellular tumor, 1 venous racemose hemangioma, 1 capillary-racemose hemangioma, 8 fibrosarcomas, 1 rhabdomyosarcoma, 1 neurosarcoma, 3 synovialsarcomas, 1 malignant mesehnchimoma, 1 mixed epithelioconnectival tumor, 5 ablastic sarcomas, 2 epitheliomas. The arteriographic aspects observed are compared with those described in the literature in order to outline the present knowledge on arteriographic semeiology and diagnosis in benign and malignant tumors of soft tissues. As concerns arteriographic semieology, seven main radiological signs are recognized by the authors, or: 1) displacement of vessels surrounding the growth; 2) dilatation of centripetal and centrifugal vessels; 3) changes in the circulation time; 4) vessels neoformation. Four main angiographic aspects of the newly formed intratumoral vascular network are described; 5) tumor impregnation by the contrast medium; 6) intratumoral blood collections; 7) arterovenous shunts. The frequency and extend of the mentioned radiological features are varying, and different arteriographic pictures may be seen according to tumors type and malignancy. In the majority of benign tumors nearly similar pictures are seen, characterized by absent or scarce vessels of normal appearance. Fibromatous tumors show a homogeneous moderate retention of the contrast medium. Vascular tumors, and particularly some types of angioma, may exhibit rather typical features which consent an angiographic diagnosis of the tumor type. As concerns malignant tumors, rather polymorphic arteriographic pictures are seen in fibrosarcomas, as to tumor vascularization and structural arrangement. Occasionally, vessels are scarce and of normal appearance, and the angiographic pattern resembles that of fibroma; in other cases vessels are more abundant. with irregular caliber and course. The greatest vascular atypia seems to correspond to the histologically most malignant variety of fibrosarcoma. A characteristic common to all observed cases of fibrosarcomas was an evident homogeneous impregnation by the contrast medium. The presence of intratumoral lacune and arterovenous shunts is exceptional. Mention is given of pictures obtained in lipo- and mixosarcomas, sarcomas of muscular origin and angiosarcomas, whereas synovialsarcomas and ablastic sarcomas are more thoroughly considered. Synovialsarcomas are scarcely known in the arteriographic literature. In the three cases observed by the authors, the arteriographic picture resembled that of some types of fibrosarcoma, with abundant and rather atypical vessels, absence of blood lacunae or shunts, regular retention of the contrast medium. These angiographic features, the site, and the roent-genographically visualized skeletal changes ought to consent a radiological diagnosis of the tumor type. In ablastic sarcomas the arteriographic picture is always characterized by a very marked vascular atypia. The frequent occurrence of intratumoral lacunae and arterovenous shunts is suggestive of the high malignancy of these forms. Side effects at the level of limb circulation are also frequently encountered. Tumor impregnation by the contrast medium varies from case to case. To conclude, arteriography is claimed to be able to reveal, in many cases, the presence of a tumor, and to determine its malignancy. The type of the tumor is hardly recognizable, except for some particular cases. Caution is needed in interpreting arteriographic pictures, for the presence of several factors may invalidate the findings. Error causes are analyzed and discussed. Arteriography cannot replace biopsy, but rather complete it as a method of diagnostic ascertainment. Arteriography seems to be clinically indicated: 1) in early diagnosis of cancer of soft tissues of extremities, mainly when the lesion is still scarcely extended or deeply situated; 2) to ascertain tumor extent, to outline its limits towards healthy soft tissues and its anatomical relationships to the bone and vessels. These findings are very significant from a therapeutical, either surgical or radiological, standpoint. 3) to check therapy results. After radiotherapy, arteriography may show a gradual normalization of the angiographic picture of malignancy. In surgically treated cases arteriography may occasionally differentiate between recurrence and cicatricial hardening or granulomatous processes at the operation site. 4) to study tumor vascularization and impregnation; number, site, and course of the supplying vessels. These data are valuable not only for surgical purposes, but also for the application of modern therapeutical methods, such as the introduction of antimitotic or radioactive substances into the afferent circulation.

The results of histological examination of lymph nodes in 18 cases of lymphosarcoma, reticulum-cell sarcoma, and Hodgkin's disease, treated with Lipiodol F I181 through the lymphatic vessels, are reported. The most significant changes induced by this therapy consisted of optically empty cavities of different shape and size; of degenerative changes of the neoplastic cells; of stromal reactions, with hystiocites and giant cells. These changes were of various degrees, according to the type of tumor and the amount of Lipiodol F I181 injected. The authors believe that the histological data presented, together with the clinical and radiological results already published, confirm the effectiveness of the intralymphatic radiotherapy in the treatment of malignant lymphomas.

The Committee for the Study of Malignant Lymphomas of the National Cancer Institute of Milano in cooperation with the Institute of Radiology, University of Milano presents a new clinical classification for lymphosarcoma and reticulum cell sarcoma as well as the method of treatment adopted in these Institutes. For primary lymph node lesions the staging is identical to that already proposed for Hodgkin's disease. Stage I: disease limited to a single peripheric lymphatic region. Within this stage two groups can he distinguished: a) involvement of one single lymph node or few nodes limited to a small area of the region (unifocal lesions); b) involvement of many nodes spread throughout the region (uniregional lesions). Stage II: disease limited to two contiguous peripheric lymphatic regions, or to few deep nodes (mediastinal, retroperitoneal). Stage III: disease limited to two non contiguous peripheric lymphatic regions, or to many peripheric and/or deep (mediastinal, retroperitoneal) regions, provided the involvement is either above or below the diaphragm. Stage IV: generalized disease with involvement of lymph nodes above and below the diaphragm, or involvement of one or more lymphatic regions with concomitant involvement of visceral organs, bones, marrow, nervous system and skin. For primary pharyngeal lesions the T.N.M. nomenclature has been adopted. T1: unifocal lesion (e.g. nasopharynx, tonsil, uvula); T2: multifocal lesions (e. g. nasopharynx and tonsil, tonsils, tonsil and base of the tongue); T3: unifocal lesion with extension beyond the anatomical confine of the site of origin (e. g. base of the skull, paranasal sinuses, jaw, orbit); T4: multifocal lesions with extension beyond the anatomical confine of the site of origin. N0: no adenopathy; N1: ipsilateral contiguous adenopathy (submental and/or cervical); N2: bilateral contiguous adenopathy; N3: bilateral contiguous and/or supravicular adenopathy (unilateral or bilateral); N4: distant adenopathy. M–-: absence of metastases; M+: presence of metastases (visceral, osseous, nervous, cutaneous). The remaining primary extranodal lesions (visceral, osseous, cutaneous, etc.) are classified as local, regional and diffuse. Systemic symptoms and signs (fatigue, fever, night sweats, more than 10% weight loss, itching, anemia, leukocytosis, lymphocytopenia, high erythrosedimentation rate) must be recorded in each case to evaluate prognosis and proper treatment but are not important for staging the disease. In all stages with primary lymph node lesions endolymphatic radiotherapy with Lipiodol F I131 is indicated (10 ml in each foot with 2–5 mc/ml giving a tissue-dose of 15-20,000 rads). This is considered as radical as well as prophylactic treatment for those lymph nodes adequatelly filled with the contrast medium. In case of non filling or incomplete filling of part of the lymph node chains, treatment will be completed with external radiation therapy. Stage I and II are treated with radical radiation therapy. No prophylactic radiotherapy is given. If systemic symptoms and signs are still present after radiotherapy a course with anticancer drugs will be administered. Radiation therapy is given with high voltage or Co60 units. In radical treatments tumor doses of at least 3,000 rads within 3–4 weeks are administered to all involved lymphatic regions. In stage III radical radiotherapy follows a course of chemotherapy. In stage IV chemotherapy is the treatment of choice. Palliative radiotherapy is given to any bulk of tumors, wherever the location, when specific symptoms can be attributed to the masses. For primary pharyngeal lesions the primary focus (T1, T2, T3, T4) is always treated with radical radiation therapy (Co60 unit) which includes in the whole Waldeyer's ring. Prophylactic radiotherapy (Co60 unit with doses not less than 3,000 rads in 3–4 weeks) is given in N0 to the ipsilateral and in N1 to the contralateral submental and cervical lymphatic regions. In N1 and N2 the lymph node bearing areas are given radical radiation therapy. In N3 are irradiated prophylactically also the contralateral submental, cervical and supraclavicular lymphatic regions if clinically free of disease. Endolymphatic radiotherapy is performed only in T1 T2 T3 T4, N3 N4, M–- or M+ cases; otherwise diagnostic lymphangiography is performed and when pathologic nodes are present or suspected they are irradiated with Co60. Chemotherapy is given after the course of radiotherapy in N2 cases only if radical treatment has not been accomplished, while is always administered in combination with radical radiotherapy in N3 cases, and is considered the treatment of choice with palliative radiation therapy in N4 and M+ cases. The drug of choice is methyl-bis-(β-chloro-ethyl)-amine HCl (HN2) 0.4 mg/kg i.v. (single dose) for those patients who did not receive any previous course of chemotherapy. Otherwise, as well as during the course of the disease and in maintenance therapy, other polyfunctional alkylating agents, but chiefly chlorambucil (0.1–0.2 mg/kg/die, p. o.), vinblastine (0.10–0.15 mg/kg/week, i.v.), alone or every two weeks in combination with small daily doses of chlorambucil (5 mg/die, p. o.), methylhydrazine, hydroxyurea, and corticosteroids will be administered according to each clinical situation. Relapses in oropharynx can be treated with intraarterial infusions of amethopterine, vinblastine and cyclophosphamide. Radical surgery followed by a course of radiotherapy is reserved for primary lymphatic involvement only in specially selected patients in Stage I with unifocal lesions. Primary involvement of stomach, small bowel and colon is treated by surgical extirpation and radiotherapy. Splenectomy, lobectomy or pneumonectomy is indicated when these viscus are the only site of involvement. During pregnancy radiation therapy is not administered below the diaphragm and chemotherapy is not given during the first 4 months. The need for one internationally accepted clinical classification for lymphosarcoma and reticulum cell sarcoma is stressed.

Due to COVID-19, the event has been postponed. AISTATS 2020 held online on August 26-28th.; International audience; We investigate and provide new insights on the sampling rule called Top-Two Thompson Sampling (TTTS). In particular, we justify its use for fixed-confidence best-arm identification. We further propose a variant of TTTS called Top-Two Transportation Cost (T3C), which disposes of the computational burden of TTTS. As our main contribution, we provide the first sample complexity analysis of TTTS and T3C when coupled with a very natural Bayesian stopping rule, for bandits with Gaussian rewards, solving one of the open questions raised by Russo (2016). We also provide new posterior convergence results for TTTS under two models that are commonly used in practice: bandits with Gaussian and Bernoulli rewards and conjugate priors.

This monograph summarizes the experience gained at the University of Milan, Italy and the National Cancer Institute in Milan in the application of endolymphatic therapy in the treatment of lymphomas. It is divided into nine chapters dealing with such topics as the status of radical and palliative treatment of malignant lymphomas, clinical and histopathological staging, diagnostic evaluation, and the natural history and spread of the disease. The authors then describe the technique and special instruments which they designed to administer endolymphatic therapy, as well as the clinical results obtained from 1961 through 1969. A total of 426 patients were treated by endolymphatic therapy; 208 had Hodgkin's disease, 95 had lymphosarcoma, and 123 had reticulum-cell sarcoma. It became obvious that homogeneous distribution of contrast medium in the lymph node is essential for successful treatment. For this reason, extravasation, lymphatic blockage, and bypassing of abnormal tumor-filled nodes were all felt to be factors which would adversely influence homogeneous distribution of the therapeutic agent. Radiographs taken before and after endolymphatic therapy show a significant decrease in the size of nodes after therapy. Recurrences and appearances of disease in new locations were rarely found if the patients were treated during early stages of the disease, but they were not infrequent in more advanced stages. Lymph nodes removed at surgery or postmortem examination were studied in order to assess the effect of irradiation. Satisfactory destruction was found close to the vacuoles in which the oil was located. This book is a concise summary of the authors' experience in endolymphatic therapy. It is doubtful that this method of therapy will be used widely, due to the uncertain distribution of contrast medium, the difficulty in calculating delivered dosages, and the fact that external radiotherapy or chemotherapy has achieved such good results. To the interested reader it becomes obvious that many questions about endolymphatic therapy remain unanswered. It is unfortunate that this monograph does not summarize the experience of other investigators in this field as well. Neverthelcss, it represents the most extensive endolymphatic therapy material available in the English language.

The retroperitoneal node chains in 36 patients with rectal and sigmoid cancer have been explored by lymphangiography (Lipiodol F). The lymphangiograms were definitely abnormal especially in the external iliac chains in 20 cases and suspicious in four. Iliac lymphadenectomy was performed in seven patients and was positive for metastatic involvement in three. The lymphangiographic findings could represent either a direct lymph pathway, connecting the rectum to the external iliac nodes, or a sign of retrograde metastases. Endolymphatic radiotherapy (Lipiodol F131I) was carried out in four patients. This therapeutic approach can be applied in patients with rectal cancer before surgery to irradiate small metastases. It is concluded that in all resectable patients with rectal, sigmoid and colon cancers lymphangiography should be routinely performed and lymphadenectomy carried out in those cases showing retroperitoneal metastases.

Many time-series such as human movement data consist of a sequence of basic actions, e.g., forehands and backhands in tennis. Automatically extracting and characterizing such actions is an important problem for a variety of different applications. In this paper, we present a probabilistic segmentation approach in which an observed time-series is modeled as a concatenation of segments corresponding to different basic actions. Each segment is generated through a noisy transformation of one of a few hidden trajectories representing different types of movement, with possible time re-scaling. We analyze three different approximation methods for dealing with model intractability, and demonstrate how the proposed approach can successfully segment table tennis movements recorded using a robot arm as haptic input device.