Immunoscintigraphy for therapy decision making and follow-up of biological therapies

With the availability of new biological therapies there is the need of more accurate diagnostic tools to noninvasively assess the presence of their targets. In this scenario nuclear medicine offers many radiopharmaceuticals for SPECT or PET imaging of many pathological conditions. The availability of monoclonal antibodies provides tools to target specific antigens involved in angiogenesis, cell cycle or modulation of the immune systems. The radiolabelling of such therapeutic mAbs is a promising method to evaluate the antigenic status of each cancer lesion or inflamed sites before starting the therapy. It may also allow to perform follow-up of such biological therapies. In the present review we provide an overview of the most studied radiolabelled antibodies for therapy decision making and follow-up of patients affected by cancer and other pathological conditions

Laparoscopic distal pancreatectomy in Italy: A systematic review and meta-analysis

Background The use of laparoscopic distal pancreatectomy (LDP) increased in the past twenty years but the real diffusion of this technique is still unknown as well as the type of centers (high or low volume) in which this procedure is more frequently performed. Data Source A systematic review was performed to evaluate the frequency of LDP in Italy and to compare indications and results in high volume centers (HVCs) and in low volume centers (LVCs). Results From 95 potentially relevant citations identified, only 5 studies were included. A total of 125 subjects were analyzed, of whom 95 (76.0%) were from HVCs and 30 (24.0%) from LVCs. The mean number of LDPs performed per year was 6.5. The mean number of patients who underwent LDP per year was 8.8 in HVCs and 3.0 in LVCs (P<0.001). The most frequent lesions operated on in HVCs were cystic tumors (62.1%, P<0.001) while, in LVCs, solid neoplasms (76.7%, P<0.001). In HVCs, malignant neoplasms were treated with LDP less frequently than in LVCs (17.9% vs 50.0%, P<0.001). Splenectomy was performed for non-oncologic reason frequenter in HVCs than in LVCs (70.2% vs 25.0%, P=0.004). The length of stay was shorter in HVCs than in LVCs (7.5 vs 11.3, P<0.001). No differences were found regarding age, gender, ductal adenocarcinoma treated, operative time, conversion, morbidity, postoperative pancreatic fistula, reoperation and margin status. Conclusions LDPs were frequently performed in Italy. The "HVC approach" is characterized by a careful selection of patients undergoing LDP. The "LVC approach" is based on the hypothesis that LDPs are equivalent both in short-term and long-term results to laparotomic approach. These data are not conclusive and they point out the need for a national register of laparoscopic pancreatectomy

Advances in targeted Alpha therapy for prostate cancer

BACKGROUND: Amongst therapeutic radiopharmaceuticals, targeted alpha therapy (TαT) can deliver potent and local radiation selectively to cancer cells as well as the tumor microenvironment and thereby control cancer while minimizing toxicity. DESIGN: In this review, we discuss the history, progress, and future potential of TαT in the treatment of prostate cancer, including dosimetry-individualized treatment planning, combinations with small-molecule therapies, and conjugation to molecules directed against antigens expressed by prostate cancer cells, such as prostate-specific membrane antigen (PSMA) or components of the tumor microenvironment. RESULTS: A clinical proof of concept that TαT is efficacious in treating bone-metastatic castration-resistant prostate cancer has been demonstrated by radium-223 via improved overall survival and long-term safety/tolerability in the phase III ALSYMPCA trial. Dosimetry calculation and pharmacokinetic measurements of TαT provide the potential for optimization and individualized treatment planning for a precision medicine-based cancer management paradigm. The ability to combine TαTs with other agents, including chemotherapy, androgen receptor (AR)-targeting agents, DNA repair inhibitors, and immuno-oncology agents, is under investigation. Currently, TαTs that specifically target prostate cancer cells expressing PSMA represents a promising therapeutic approach. Both PSMA-targeted actinium-225 and thorium-227 conjugates are under investigation. CONCLUSIONS: The described clinical benefit, safety and tolerability of radium-223 and the recent progress in TαT trial development suggest that TαT occupies an important new role in prostate cancer treatment. Ongoing studies with newer dosimetry methods, PSMA targeting, and novel approaches to combination therapies should expand the utility of TαT in prostate cancer treatment

Multioutput regression of noisy time series using convolutional neural networks with applications to gravitational waves

In this thesis I implement a deep learning algorithm to perform a multioutput regression. The dataset is a collection of one dimensional time series arrays, corresponding to simulated gravitational waveforms emitted by a black hole binary, and labelled by the masses of the two black holes. In addition, white Gaussian noise is added to the arrays, to simulate a signal detection in the presence of noise. A convolutional neural network is trained to infer the output labels in the presence of noise, and the resulting model generalizes over many order of magnitudes in the noise level. From the results I argue that the hidden layers of the model succesfully denoise the signals before the inference step. The entire code is implemeted in the form of a Python module, and the neural network is written in PyTorch. The training of the network is speeded up using a single GPU, and I report about efforts to improve the scaling of the training time with respect to the size of the training sample

Ion diffusion modelling of Fricke-agarose dosemeter gels

In Fricke-agarose gels, an accurate determination of the spatial dose distribution is hindered by the diffusion of ferric ions. In this work, a model was developed to describe the diffusion process within gel samples of finite length and, thus, permit the reconstruction of the initial spatial distribution of the ferric ions. The temporal evolution of the ion concentration as a function of the initial concentration is derived by solving Fick's second law of diffusion in two dimensions with boundary reflections. The model was applied to magnetic resonance imaging data acquired at high spatial resolution (0.3 mm) and was found to describe accurately the observed diffusion effect

Scalar charge of black holes in Einstein-Maxwell-dilaton theory

We show that the monopole scalar charge of black holes in Einstein--Maxwell--dilaton theory is proportional to the electric potential at the event horizon, with a proportionality factor given by (minus) the scalar coupling constant. We also show that the scalar charge, in the weak electric charge limit, does not depend on the black hole spin. This result can be very useful to circumvent spin degeneracy issues when testing the theory against gravitational waves observations.Comment: v2: 6 pages, corrected typos, references adde

Black holes beyond general relativity: theoretical and phenomenological developments.

In four dimensions, general relativity is the only viable theory of gravity satisfying the requirements of diffeoinvariance and strong equivalence principle. Despite this aesthetic appeal, there are theoretical and experimental reasons to extend gravity beyond GR. The most promising tests and bounds are expected to come from strong gravity observations. The past few years have seen the rise of gravitational wave astronomy, which has paved the way for strong gravity observations. Future GW observations from the mergers of compact objects will be able to constrain much better possible deviations from GR. Therefore, an extensive study of compact objects in modified theories of gravitation goes in parallel with these experimental efforts. In this PhD Thesis we concentrate on black holes. Black holes act as testbeds for modifications of gravity in several ways. While in GR they are extremely simple objects, in modified theories their properties can be more complex, and in particular they can have hair. The presence of hair changes the geometry felt by test fields and it modifies the generation of GW signals. Moreover, black holes are the systems in which the presence of singularities is predicted by classical gravity with the highest level of confidence: this is not only true in GR, but also in most of the modified gravity theories formulated in classical terms as effective field theories. Singularities are regarded as classical artifacts to be cured by quantum gravity effects. Therefore, considering mechanisms of singularity resolutions is a theoretical arena to study the form of these effects. The Thesis presents theoretical contributions to all these aspects of black hole physics. The work is organized following three main topics: black holes with universal horizons, hairy black holes in Einstein-Maxwell-dilaton theory and regular black holes. These models originate from various motivations: black holes with universal horizons are found in modified gravity theories which break local Lorentz symmetry; Einstein-Maxwell-dilaton black holes originate in string theory and in lower dimensional compactifications, but they also serve as proxies for black holes in theories propagating additional degrees of freedom; regular black holes are motivated by the efforts to understand how quantum gravity solves the classical singularities. In each of the above cases, we present results which appear to be relevant for the follow up research in their respective fields. We also emphasize that, besides the contextual significance of our results, we also developed thechniques for addressing the respective problems, which can be useful well beyond the specific cases considered in this Thesis

Why are you not breeding?

Conservation biologists have long faced the very challenging task of large carnivore conservation. Both their hunting habits and their very specific ecology make their conservation particularly difficult. Wolverines (Gulo g. gulo) are a good example of this. The population of wolverines is close to extinction due to human persecution and habitat loss. The European Association of Zoos and Aquaria (EAZA) introduced the European Endangered Species Program (EEP) for the Wolverine in 1994 but it experiences some irregular breeding. The aim of this study was to identify factors that could be connected to breeding success in these captive wolverines regarding the characteristics of the enclosures, the wolverine biology, the characteristics of the institutions and the influences of the human-animal interactions. To this end, an online survey was developed and sent to all holders of wolverines included in the EEP program. Overall, no main factor or group of factors investigated in this study seemed to be the clear explanation of the differences in breeding success between institutions participating in the Wolverine EEP Program, partly because of the small sample size. However, enclosure size and keeper effect could actually have had an effect on their breeding and further research on these topics is needed. Emphasis has been given to provide the best adequate environment for a wolverine and have good husbandry practices

Improving the welfare of the Amur leopards (Panthera pardus orientalis) at Nordens Ark (Sweden)

Since recent years, people do not only want to prevent animal cruelty anymore, but also want to improve their welfare. Therefore, zoo institutions are under pressure to assure the wellbeing of their animals. And even though they work very hard to achieve this, it is not an easy job. Carnivores, most notably solitary felids, are amongst the most difficult species for whom to develop a proper environment. Previous studies conducted on the two Amur leopards currently living at Nordens Ark recorded signs of stress and pacing. However, no previous individual assessment had been carried out to evaluate their welfare and find out the possible reasons behind their behavior. The aim of this study was (1) to evaluate and improve the welfare of the two Amur leopards currently living at Nordens Ark, and (2) to find out if making changes in their environment could be a way to improve their welfare. To this end, a behavioral study was carried out during different periods of time on both individuals, while being exposed to four changes in their environment concerning training, increased zookeeper presence, increased environmental enrichment and visual barriers. Overall, these changes seem to have had a positive effect on both leopards. However, they still showed signs of poor welfare and more effort needs to be put to ensure their best welfare quality. Emphasis has been given to provide varying enrichment and training, and increasing presence of keepers. Moreover, individual differences due to different personalities should be taken into consideration