Purpose:
M5L, a fully automated computer‐aided detection (CAD) system for the detection and segmentation of lung nodules in thoracic computed tomography (CT), is presented and validated on several ...image datasets.
Methods:
M5L is the combination of two independent subsystems, based on the Channeler Ant Model as a segmentation tool lung channeler ant model (lungCAM) and on the voxel‐based neural approach. The lungCAM was upgraded with a scan equalization module and a new procedure to recover the nodules connected to other lung structures; its classification module, which makes use of a feed‐forward neural network, is based of a small number of features (13), so as to minimize the risk of lacking generalization, which could be possible given the large difference between the size of the training and testing datasets, which contain 94 and 1019 CTs, respectively. The lungCAM (standalone) and M5L (combined) performance was extensively tested on 1043 CT scans from three independent datasets, including a detailed analysis of the full Lung Image Database Consortium/Image Database Resource Initiative database, which is not yet found in literature.
Results:
The lungCAM and M5L performance is consistent across the databases, with a sensitivity of about 70% and 80%, respectively, at eight false positive findings per scan, despite the variable annotation criteria and acquisition and reconstruction conditions. A reduced sensitivity is found for subtle nodules and ground glass opacities (GGO) structures. A comparison with other CAD systems is also presented.
Conclusions:
The M5L performance on a large and heterogeneous dataset is stable and satisfactory, although the development of a dedicated module for GGOs detection could further improve it, as well as an iterative optimization of the training procedure. The main aim of the present study was accomplished: M5L results do not deteriorate when increasing the dataset size, making it a candidate for supporting radiologists on large scale screenings and clinical programs.
Purpose:
This paper describes the system for the dose delivery currently used at the Centro Nazionale di Adroterapia Oncologica (CNAO) for ion beam modulated scanning radiotherapy.
Methods:
CNAO ...Foundation, Istituto Nazionale di Fisica Nucleare and University of Torino have designed, built, and commissioned a dose delivery system (DDS) to monitor and guide ion beams accelerated by a dedicated synchrotron and to distribute the dose with a full 3D scanning technique. Protons and carbon ions are provided for a wide range of energies in order to cover a sizable span of treatment depths. The target volume, segmented in several layers orthogonally to the beam direction, is irradiated by thousands of pencil beams which must be steered and held to the prescribed positions until the prescribed number of particles has been delivered. For the CNAO beam lines, these operations are performed by the DDS. The main components of this system are two independent beam monitoring detectors, called BOX1 and BOX2, interfaced with two control systems performing the tasks of real‐time fast and slow control, and connected to the scanning magnets and the beam chopper. As a reaction to any condition leading to a potential hazard, a DDS interlock signal is sent to the patient interlock system which immediately stops the irradiation. The essential tasks and operations performed by the DDS are described following the data flow from the treatment planning system through the end of the treatment delivery.
Results:
The ability of the DDS to guarantee a safe and accurate treatment was validated during the commissioning phase by means of checks of the charge collection efficiency, gain uniformity of the chambers, and 2D dose distribution homogeneity and stability. A high level of reliability and robustness has been proven by three years of system activity needing rarely more than regular maintenance and working with 100% uptime. Four identical and independent DDS devices have been tested showing comparable performances and are presently in use on the CNAO beam lines for clinical activity.
Conclusions:
The dose delivery system described in this paper is one among the few worldwide existing systems to operate ion beam for modulated scanning radiotherapy. At the time of writing, it has been used to treat more than 350 patients and it has proven to guide and control the therapeutic pencil beams reaching performances well above clinical requirements. In particular, in terms of dose accuracy and stability, daily quality assurance measurements have shown dose deviations always lower than the acceptance threshold of 5% and 2.5%, respectively.
Background:
Giant cell arteritis (GCA) is the most common primary systemic vasculitis in western countries with the highest incidence among persons 70–79 years of age. Treatment has been with ...glucocorticoids (GCs) alone for many decades but recently Tocilizumab (TCZ) has demonstrated efficacy in reducing GC dose and flare rates in patients with GCA. Therefore, both early diagnosis and regular monitoring are necessary for the correct management of GCA. The COVID-19 pandemic has led to decisions by the governments of the countries involved, aimed above all at reducing the contagion. This has also led to reductions in health activities, limiting them to those of urgency by reducing or canceling checkups involving the risk of a time gap which for the GCA meant the interruption of clinical monitoring and therapeutic adjustment. At the same time, the pandemic situation has stimulated remote monitoring activities, through telephone contacts or video calls carried out by the rheumatologist. EULAR identified a minimal data set aimed at research and for clinical use, which includes the main clinical and instrumental data to be taken into consideration in monitoring the patient. For many data a clinical examination is not necessary but an interview is sufficient. We activated the TELEMACOV protocol (TELEmedicine and Management of the patient affected by giant cell arteritis during the COVid-19 pandemic) monitoring the follow-up of patients affected by GCA through telemedicine tools in order to maintain an effective and risk-free follow-up in a pathology with a high risk of relapse.
Objectives:
The purpose of the study is to evaluate the effectiveness of telemedicine in the follow-up of the patient with GCA.
Methods:
We evaluated patients (pts) with a clinical diagnosis of GCA (received in previous periods) who were admitted to the our Rheumatology Unit. They were monitored monthly by telephone from 9 March to 9 June 2020 (during lockdown). All patients were asked questions divided according to the sub-groups listed below:
- Onset of new symptoms or their recurrence
- Exams carried out
- Current therapy
- Satisfaction of telephone call
Results:
We performed 148 remote monitoring visits in 37 pts. The cohort was mainly composed by female (77,8%) and had a mean age of 71,85 ± 9,25 years. They were affected by GCA, with a mean duration of 5,3±2,3 months. The characteristics of these pts and the course of the disease are reported in Table 1. Pts treated with TCZ reduced their GC dose more than patients treated with GC alone (p: 0.032). Only one patient (treated with GC alone) had an ocular flare with the need to increase the dosage of the GC with good response and rapid improvement. Furthermore, all patients considered this type of monitoring very satisfactory according to the Likert scale (1-5) with mean 4,4±0,2.
Conclusion:
Our study has shown how telemedicine can be well used in pts with GCA as a possible alternative, for a limited period, to traditional visits, especially in a fragile population such as the elderly and more exposed to the risk of SARS-COV2 infection.
References:
1Ehlers L et al. Ann Rheum Dis 2019 Sep;78(9):1160-1166
2Wagner E et al. Prim Care. 2012 Jun;39(2):241-59.
Table 1.
Disease course and remote monitoring
Parameters
Baseline (at diagnosis
)
Pre-lock down
First Interview
Second Interview
Patients treated with only GC (19 pts
)
Mean
SD
Mean
SD
Mean
SD
Mean
SD
ESR
74,08
23,95
13,02
8,2
12,75
6,42
9,84
6,63
CRP mg/l
47,4
42,2
1,01
1,1
1,55
2,29
1,56
2,24
Hgb mg/dl
11,6
2,6
13,2
2,24
12,75
3,19
13,58
2,12
PGA (1-10)
7,55
2,05
2,71
1,79
2,24
1,59
2,15
1,04
EGA (1-10)
6,99
1,85
2,19
1,42
1,97
1,13
1,43
0,97
GC mg
52,72
18,3
10,1
6,95
7,6
4,51
6,67
3,1
Patients treated with GC and TCZ (18 pt
)
ESR
74,56
36,58
11,3
3,85
9,89
4,71
3,37
4,4
CRP mg/l
47,8
41,7
1,13
0,65
1,58
0,85
1,62
0,73
Hgb mg/dl
11,36
3,88
12,98
4,91
12,43
4,3
13,25
5,15
PGA (1-10)
7,14
3,11
2,47
2,15
1,89
0,4
1,93
0,72
EGA (1-10)
6,93
2,72
0,95
0,73
0,68
0,43
0,41
0,72
GC mg
51,76
18,85
8,04
4,38
5,88
3,92
4,16
4,32
PGA: Patient Global Assessment EGA: Evaluator Global Assessment;
Disclosure of Interests:
None declared
Background:
Systemic Sclerosis (SSc) is an autoimmune rheumatic disease characterized by excessive production and accumulation of collagen in the skin and internal organs and by injuries to small ...arteries.
Impairment of the musculoskeletal system is one of the main causes of disability in SSc, indeed, about 90% of these patients have a loss of hand function. To date, the degree of skin involvement is evaluated through a semi-quantitative method called Rodnan Skin Score (RSS) or Modified-RSS (MRSS). However, MRSS is a method that has limitations related to the operator and his experience and does not provide information on joint mobility.
Arduino® is an open source integrated online platform based on easy to use hardware and software. It is a system for creating interactive projects by inserting a special configuration code, using the Arduino® development environment. Through this platform it is possible to create electronic devices with specific purposes to lead the possibility of integrating different kits (eg types of sensors) in relation to the object of study.
Objectives:
We have therefore created an electronic instrument (Sclerodermic Hand Sensor - SHS) independent operator and easily reproducible in order to measure the degree of mobility (flexion) of the hand in patients with SSc (Fig.1). The aim was to evaluate whether the SHS was able to highlight significant differences between patients with SSc and healthy patients.
Methods:
We recruited 20 female patients with SSc according to ACR criteria with a mean age of 50.8 ± 15.5 years and 20 healthy (HC) patients with a mean age of 44.3 ± 10.8 years (Tab.1), in order to test the effectiveness and sensitivity of the SHS tool.
Results:
The results showed a significant difference between the two groups of patients (SSc vs HC) independent of the measurement method used as expected (Goniometer SSc / HC: Δ45.80 ° p: 0.003 SHS SSc / HC: Δ65.17 ° p: 0.002, Fig.1c), however the device created with Arduino® proved to be more sensitive than the goniometric measurement in detecting the degree of joint flexion (p: 0.002). The flexion sensor, indeed, unlike the goniometer, evaluates the simultaneous articular excursion of the entire finger (MCF, IFP and IFD) and not just one segment (Fig.1).
Conclusion:
This technology application, thanks to the creation of dedicated electronic devices, allows the physicians to be supported in clinical practice with independent operating tools.
The tool we propose could be a valid support in accurately assessing the joint and indirectly skin involvement of sclerodactyly in this type of patient, especially in the context of a clinical trial to evaluate the efficacy of a treatment.
Further studies are needed to compare with other methods to assess hand disability in SSc such as the use of HAMIS (Hand Mobility in Scleroderma) test.
References:
1Sandqvist G et al. J Rheumatol. 2016 Jul;43(7):1356-62.
2
https://www.arduino.cc
.
Table 1.
SSc Patients Characteristics
Chararcteristics
SSc
Patients (n°, subset D=Diffuse; L=Limited)
20 (9D/11L)
Age, mean ± SD years
50.8 ± 15.5
Duration of Raynaud’s Phenomenon (mean ± SD years)
12.8 ± 4.4
Duration of SSc (mead ± SD years)
8.4 ± 3.6
MRSS (mean ± SD years)
15.9 ± 5.3
Disclosure of Interests:
None declared
•A two stage process is proposed for the production of poly(hydroxyalkanoates) from OMW at pilot scale.•A unique polymer with both scl- and mcl-monomeric units, i.e. 3HB and 3HO, was produced for the ...first time from wastes and mixed cultures.•Clarification of the acidified waste via alum enhanced final yields of PHAs.•Composition and properties of PHAs are not affected by the presence of solids in acidified OMW.•Scaling up of the process leads to enhanced yields and productivities.
The operational efficiency of a two stage pilot scale system for polyhydroxyalkanoates (PHAs) production from three phase olive oil mill wastewater (OMW) was investigated in this study. A mixed anaerobic, acidogenic culture derived from a municipal wastewater treatment plant, was used in the first stage, aiming to the acidification of OMW. The effluent of the first bioreactor that was operated in continuous mode, was collected in a sedimentation tank in which partial removal of the suspended solids was taking place, and was then forwarded to an aerobic reactor, operated in sequential batch mode under nutrient limitation. In the second stage an enriched culture of Pseudomonas sp. was used as initial inoculum for the production of PHAs from the acidified waste. Clarification of the acidified waste, using aluminium sulphate which causes flocculation and precipitation of solids, was also performed, and its effect on the composition of the acidified waste as well as on the yields and properties of PHAs was investigated. It was shown that clarification had no significant qualitative or quantitative effect on the primary carbon sources, i.e. short chain fatty acids and residual sugars, but only on the values of total suspended solids and total chemical oxygen demand of the acidified waste. The type and thermal characteristics of the produced PHAs were also similar for both types of feed. However the clarification of the waste seemed to have a positive impact on final PHAs yield, measured as gPHAs/100g of VSS, which reached up to 25%. Analysis of the final products via nuclear magnetic resonance spectroscopy revealed the existence of 3-hydroxybutyrate (3HB) and 3-hydroxyoctanoate (HO) units, leading to the conclusion that the polymer could be either a blend of P3HB and P3HO homopolymers or/and the 3HB-co-3HO co-polymer, an unusual polymer occurring in nature with advanced properties.
A strain of embryonic human kidney cells (HEK293) was transiently co-transfected with the expression vectors coding for the α- and β-subunits of human thyroid-stimulating hormone (hTSH), and, for the ...first time, a human cell-derived recombinant hTSH was synthesized and extensively characterized. The purification strategy involving two steps provided an overall yield of 55% and a purity level > 90%. The purified material (hTSH-HEK) was analyzed and compared to a CHO-derived recombinant preparation (hTSH-CHO) and to a pituitary-derived (hTSH-Pit) preparation. The three preparations showed an equivalent purity (> 95%) with a hTSH-HEK molecular mass 2.1% lower than that of hTSH-CHO and 2.7% higher than that of hTSH-Pit. Remarkable differences were found in the carbohydrate moiety, the lowest sialic acid content and highest fucose content being observed in hTSH-HEK. In vivo biological activity was confirmed for the three preparations, the hTSH-HEK bioactivity being 39 and 16% lower than those of hTSH-CHO and hTSH-Pit, respectively. The hTSH-HEK circulatory half-life (
t
1/2
) was also shorter than those of hTSH-CHO (1.5-fold) and hTSH-Pit (1.2-fold). According to these findings, HEK-293-derived hTSH can be considered to be useful for clinical applications, in view as well of its human origin and particular carbohydrate composition.
Various amounts (1, 3 and 5
wt%) of a non-modified natural montmorillonite clay (Cloisite
® Na
+) or of an ion-exchanged clay modified with quaternary ammonium salt (Cloisite
® 25A) were dispersed in ...a recycled poly(ethylene terephthalate) matrix (rPET) by a melt intercalation process. Microphotographs of composite fracture surfaces bring evidence that particles of Cloisite
® 25A are much better dispersed in the rPET matrix than those of Cloisite
® Na
+. Moreover, WAXS measurements indicate that the lamellar periodicity of Cloisite
® 25A is increased in the composites, which evidences intercalation of rPET between silicate layers (lamellae) of the clay. In the case of Cloisite
® Na
+, a very small thickening of lamellae due to mixing with rPET indicates only minute intercalation.
Uniaxial tensile tests show that both clays increase the modulus of the rPET composites; more effective Cloisite
® 25A accounts for a 30% increase at loading of 5
wt%. Yield strength remains practically unaffected by the used fractions of the clays while tensile strength slightly decreases with the clay content; in parallel, strain at break dramatically drops. Tensile compliance of the composites is virtually independent of applied stress up to 26 MPa. Essential part of the compliance corresponds to the elastic time-independent component, while the viscoelastic component is low corresponding only to a few percent of the compliance even at relatively high stresses. The compliance of the composites is only slightly lower than that of the neat rPET, the reinforcing effect of Cloisite
® 25A being somewhat stronger. Both clays have beneficial effect on the dimensional stability of the composites since—in contrast to the neat rPET—the creep rate does not rise at long creep periods.
An alternative treatment for growth hormone deficiency based on hGH-DNA administration, followed by electro gene transfer, was investigated by injecting the plasmid into surgically exposed or ...non-exposed quadriceps or tibialis muscle of immunodeficient "little" mice.
An optimization of electrotransfer conditions via a new combination of high/low voltage pulses is presented. After 3 days, serum hGH was determined and in a 28-day assay, the relative growth parameters were compared.
Both groups exhibited similar results: 5.0 ± 2.2 (SD) and 3.5 ± 0.9 ng hGH/ml (P>0.05; n=7) for the exposed quadriceps and non-exposed tibialis treatments, respectively. The final body weight increases were 16.1% for the quadriceps and 18.9% for the tibialis group. The tail and nose-to-tail length increases were 4.5% and 7.1% for the quadriceps and 4.8 and 4.6% for the tibialis group. The right and left femur length increases, obtained from radiographic measurements, were 16.9% and 12.7% for the quadriceps and 19.4% and 12.3% for the tibialis, respectively. A non-significant difference between exposed quadriceps and non-exposed tibialis treatments (P=0.48) was confirmed via a completely integrated statistical analysis. Circulating mIGF-1 levels were 126 ± 47, 106 ± 93 (P>0.05) and 38 ± 15 ng/ml for the quadriceps, tibialis and saline treatments, respectively.
These results show that hGH-DNA administration into non-exposed tibialis muscle followed by the new HV/LV electrotransfer protocol was an equally efficient, less traumatic treatment, much more suitable for pre-clinical testing than administration into exposed quadriceps.
Treatment quality assessment is a crucial feature for both present and next-generation ion therapy facilities. Several approaches are being explored, based on prompt radiation emission or on PET ...signals by Formula: see text-decaying isotopes generated by beam interactions with the body. In-beam PET monitoring at synchrotron-based ion therapy facilities has already been performed, either based on inter-spill data only, to avoid the influence of the prompt radiation, or including both in-spill and inter-spill data. However, the PET images either suffer of poor statistics (inter-spill) or are more influenced by the background induced by prompt radiation (in-spill). Both those problems are expected to worsen for accelerators with improved duty cycle where the inter-spill interval is reduced to shorten the treatment time. With the aim of assessing the detector performance and developing techniques for background reduction, a test of an in-beam PET detector prototype was performed at the CNAO synchrotron-based ion therapy facility in full-beam acquisition modality. Data taken with proton beams impinging on PMMA phantoms showed the system acquisition capability and the resulting activity distribution, separately reconstructed for the in-spill and the inter-spill data. The coincidence time resolution for in-spill and inter-spill data shows a good agreement, with a slight deterioration during the spill. The data selection technique allows the identification and rejection of most of the background originated during the beam delivery. The activity range difference between two different proton beam energies (68 and 72 MeV) was measured and found to be in sub-millimeter agreement with the expected result. However, a slightly longer (2 mm) absolute profile length is obtained for in-spill data when compared to inter-spill data.
The earliest clinical manifestation of SSc is usually Raynaud’s phenomenon, a small-arteries vasospasm driven by vascular tone dysregulation and microcirculatory abnormalities, resulting in digital ...ulcers (DU) in up to 50% of patients. Many cytokines as well as growth factors have been shown to play a role in promoting vascular smooth muscle cell proliferation and fibroblast activation, leading to ischemic damage as well as skin fibrosis. We aim to investigate a possible difference in venous and arterial blood levels of many cytokines (Th1- and Th17-related), GM-CSF, and endothelin-1 (ET1) in patients with and without DU. In the same patients, the correlations between capillary damage, evaluated by nailfold videocapillaroscopy (NVC), extension of skin fibrosis, calculated by modified Rodnan skin score (mRSS), and cytokines, ET-1, and GM-CSF levels were also measured. Patients with DU showed venous levels of IL-1β (p=0.024), IL-6 (p=0.012), IL-22(p=0.006), and TGF-β (p=0.046) significantly higher compared to arterial levels and arterial levels of GM-CSF and TNF-alpha significantly higher compared to venous levels (p<0.001). NVC abnormalities were correlated with arterial TNFa and venous IL22, IL23, and IL17 levels and negatively correlated with venous ET-1 levels, whereas mRSS showed a negative correlation with IL-21(ρ = −0.427, p=0.050). The increased Th17-cytokine levels in venous compared to arterial blood of patients with DU suggest local cytokine production on ulcer site. The higher TNFa and GM-CSF levels in arterial blood of DU patients support the attempt to mitigate the hypoxic damage, and the correlation between Th17-cytokines, mRSS, NVC, and ET1 agrees with the potent profibrotic stimulus at the onset of the disease, which decreases as the SSc progresses.
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