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The adequate determination and detection of explosive molecules is key to introducing improvements in areas related to safety, whose progress depends on an adequate and rapid determination of dangerous substances. To detect explosives down to the molecular level and accurately discriminate between different but somehow similar substances, it is necessary to design sensors that can differentiate them uniquely and efficiently. In this study, we present a new generation nanoscale sensor based on carbon nanotubes with an adapted nanopore shape that is capable of effectively discriminating between five types of explosive compounds (TATP, RDX, PENT, HMX and DNT). We show that the interaction of each compound with the walls of the nanotubes induces changes in transmission and current that allows clear differentiation of each type of molecule. Interestingly, the transport properties do not depend on the orientation of the molecules within the nanopore in most cases, making it a robust device with high reproducibility and stability. The results also show that these systems can lead to relatively high thermoelectric performances and, furthermore, the Seebeck coefficient can be used to discriminate between them.
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In addition to triggers such as ureteral stones or pyelonephritis, the common symptom of flank pain can be associated with a whole range of conditions. This SOP is intended to give doctors in the emergency department an overview of the possible causes. Based on medical history, clincal examination including sonography and laboratory diagnostics, important differential diagnoses are addressed and an imaging algorithm is presented.
Subject(s)
Flank Pain , Humans , Flank Pain/etiology , Diagnosis, Differential , Ultrasonography , AlgorithmsABSTRACT
The fast and precise selective sensing of DNA nucleobases is a long-pursued method that can lead to huge advances in the field of genomics and have an impact on aspects such as the prevention of diseases, health enhancement, and, in general, all types of medical treatments. We present here a new type of nanoscale sensor based on carbon nanotubes with a specific geometry that can discriminate the type of nucleobase and also its angle of orientation. The proper differentiation of nucleobases is essential to clearly sequence DNA chains, while angular discrimination is key to improving the sensing selectivity. We perform first-principle and quantum transport simulations to calculate the transmission, conductance, and current of the nanotube-based nanoscale sensor in the presence of the four nucleotides (A, C, G, and T), each of them rotated 0, 90, 180, or 270°. Our results show that this system is able to effectively discriminate between the four nucleotides and their angle of orientation. We explain these findings in terms of the interaction between the phosphate group of the nucleotide and the nanotube wall. The phosphate specifically distorts the electronic structure of the nanotube depending on the distance and the orientation and leads to nontrivial changes in the transmission. This work provides a method for finer and more precise sequential DNA chains.
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RATIONALE & OBJECTIVE: Hyponatremia is the most common electrolyte disorder and is associated with significant morbidity and mortality. This study investigated neurocognitive impairment, brain volume, and alterations in magnetic resonance imaging (MRI)-based measures of cerebral function in patients before and after treatment for hyponatremia. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Patients with presumed chronic hyponatremia without signs of hypo- or hypervolemia treated in the emergency department of a German tertiary-care hospital. EXPOSURE: Hyponatremia (ie, plasma sodium concentration [Na+]<125mmol/L) before and after treatment leading to [Na+]>130mmol/L. OUTCOMES: Standardized neuropsychological testing (Mini-Mental State Examination, DemTect, Trail Making Test A/B, Beck Depression Inventory, Timed Up and Go) and resting-state MRI were performed before and after treatment of hyponatremia to assess total brain and white and gray matter volumes as well as neuronal activity and its synchronization. ANALYTICAL APPROACH: Changes in outcomes after treatment for hyponatremia assessed using bootstrapped confidence intervals and Cohen d statistic. Associations between parameters were assessed using correlation analyses. RESULTS: During a 3.7-year period, 26 patients were enrolled. Complete data were available for 21 patients. Mean [Na+]s were 118.4mmol/L before treatment and 135.5mmol/L after treatment. Most measures of cognition improved significantly. Comparison of MRI studies showed a decrease in brain tissue volumes, neuronal activity, and synchronization across all gray matter after normalization of [Na+]. Volume effects were particularly prominent in the hippocampus. During hyponatremia, synchronization of neuronal activity was negatively correlated with [Na+] (r=-0.836; 95% CI, -0.979 to-0.446) and cognitive function (Mini-Mental State Examination, r=-0.523; 95% CI, -0.805 to-0.069; DemTect, r=-0.744; 95% CI, -0.951 to-0.385; and Trail Making Test A, r=0.692; 95% CI, 0.255-0.922). LIMITATIONS: Small sample size, insufficient quality of several MRI scans as a result of motion artifact. CONCLUSIONS: Resolution of hyponatremia was associated with improved cognition and reductions in brain volumes and neuronal activity. Impaired cognition during hyponatremia is closely linked to increased neuronal activity rather than to tissue volumes. Furthermore, the hippocampus appears to be particularly susceptible to hyponatremia, exhibiting pronounced changes in tissue volume. PLAIN-LANGUAGE SUMMARY: Hyponatremia is a common clinical problem, and patients often present with neurologic symptoms that are at least partially reversible. This study used neuropsychological testing and magnetic resonance imaging to examine patients during and after correction of hyponatremia. Treatment led to an improvement in patients' cognition as well as a decrease in their brain volumes, spontaneous neuronal activity, and synchronized neuronal activity between remote brain regions. Volume effects were particularly prominent in the hippocampus, an area of the brain that is important for the modulation of memory. During hyponatremia, patients with the lowest sodium concentrations had the highest levels of synchronized neuronal activity and the poorest cognitive test results.
Subject(s)
Brain , Hyponatremia , Magnetic Resonance Imaging , Humans , Male , Female , Prospective Studies , Middle Aged , Brain/diagnostic imaging , Brain/pathology , Aged , Chronic Disease , Neuropsychological Tests , Cohort Studies , AdultABSTRACT
The proper detection of drug molecules is key for applications that have an impact in several fields, ranging from medical treatments to industrial applications. In case of illegal drugs, their correct and fast detection has important implications that affect different parts of society such as security or public health. Here we present a method based on nanoscale sensors made of carbon nanotubes modified with dopants that can detect three types of drug molecules: mephedrone, methamphetamine and heroin. We show that each molecule produces a distinctive feature in the density of states that can be used to detect it and distinguish it from other types of molecules. In particular, we show that for semiconducting nanotubes the inclusion of molecules reduces the gap around the Fermi energy and produces peaks in the density of states below the Fermi energy at positions that are different for each molecule. These results prove that it is possible to design nanoscale sensors based on carbon nanotubes tailored with dopants, in such a way that they might be able to discriminate between different types of compounds and, especially, drug molecules whose proper recognition has important consequences in different fields.
Subject(s)
Nanotubes, Carbon , Pharmaceutical Preparations , Pharmaceutical Preparations/analysisABSTRACT
OBJECTIVE: Achieving recommended targets of sodium correction is challenging to physicians treating hyponatraemia. Plasma sodium has to be increased effectively, yet overcorrection must be prevented. This is often hampered by a high variability of responses to treatment. Here, we sought to delineate factors influencing sodium evolution. DESIGN: We retrospectively analysed 3460 patients from the multinational Hyponatraemia Registry comprising a wide range of hyponatraemia aetiologies and treatment strategies. METHODS: Multivariable linear mixed effects models were applied to identify predictors of plasma sodium evolution within the first 24â h of treatment. RESULTS: Evolution of sodium levels over time showed a curvilinear pattern with steeper rise at earlier time points. Baseline sodium showed the most pronounced impact with an additional increment of 3.12â mEq/L for every 10â mEq/L initial sodium reduction. With sodium increments of 1.9â mEq/L and 1.4â mEq/L per 24â h, respectively, the entities hypovolaemic and thiazide-associated hyponatraemia were independent factors for sodium evolution. Therapeutic regimens using hypertonic saline (4.6â mEq/L/24â h), tolvaptan (3.4â mEq/L/24â h), or combination therapy (2.6â mEq/L/24â h) were also associated with a significantly larger sodium rise when compared with no active treatment. CONCLUSIONS: Choice and dosing of active hyponatraemia therapy should be adjusted not only according to aetiology but most importantly to pretreatment sodium. Although counterintuitive, less aggressive therapy in more profound hyponatraemia might be safer but yet effective at least in less severe cases.
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Hyponatremia , Humans , Hyponatremia/drug therapy , Sodium , Retrospective Studies , Saline Solution, Hypertonic , RegistriesABSTRACT
INTRODUCTION: A rapid deploy of unexpected early impact of the COVID pandemic in Spain was described in 2020. Oncology practice was revised to facilitate decision-making regarding multimodal therapy for prevalent cancer types amenable to multidisciplinary treatment in which the radiotherapy component searched more efficient options in the setting of the COVID-19 pandemic, minimizing the risks to patients whilst aiming to guarantee cancer outcomes. METHODS: A novel Proton Beam Therapy (PBT), Unit activity was analyzed in the period of March 2020 to March 2021. Institutional urgent, strict and mandatory clinical care standards for early diagnosis and treatment of COVID-19 infection were stablished in the hospital following national health-authorities' recommendations. The temporary trends of patients care and research projects proposals were registered. RESULTS: 3 out of 14 members of the professional staff involved in the PBR intra-hospital process had a positive test for COVID infection. Also, 4 out of 100 patients had positive tests before initiating PBT, and 7 out of 100 developed positive tests along the weekly mandatory special checkup performed during PBT to all patients. An update of clinical performance at the PBT Unit at CUN Madrid in the initial 500 patients treated with PBT in the period from March 2020 to November 2022 registers a distribution of 131 (26%) pediatric patients, 63 (12%) head and neck cancer and central nervous system neoplasms and 123 (24%) re-irradiation indications. In November 2022, the activity reached a plateau in terms of patients under treatment and the impact of COVID pandemic became sporadic and controlled by minor medical actions. At present, the clinical data are consistent with an academic practice prospectively (NCT05151952). Research projects and scientific production was adapted to the pandemic evolution and its influence upon professional time availability. Seven research projects based in public funding were activated in this period and preliminary data on molecular imaging guided proton therapy in brain tumors and post-irradiation patterns of blood biomarkers are reported. CONCLUSIONS: Hospital-based PBT in European academic institutions was impacted by COVID-19 pandemic, although clinical and research activities were developed and sustained. In the post-pandemic era, the benefits of online learning will shape the future of proton therapy education.
Subject(s)
COVID-19 , Head and Neck Neoplasms , Proton Therapy , Humans , Child , Pandemics/prevention & control , COVID-19/epidemiology , HospitalsABSTRACT
Photosensitivity is a neurological disorder in which a person's brain produces epileptic discharges, known as Photoparoxysmal Responses (PPRs), when it receives certain visual stimuli. The current standardized diagnosis process used in hospitals consists of submitting the subject to the Intermittent Photic Stimulation process and attempting to trigger these phenomena. The brain activity is measured by an Electroencephalogram (EEG), and the clinical specialists manually look for the PPRs that were provoked during the session. Due to the nature of this disorder, long EEG recordings may contain very few PPR segments, meaning that a highly imbalanced dataset is available. To tackle this problem, this research focused on applying Data Augmentation (DA) to create synthetic PPR segments from the real ones, improving the balance of the dataset and, thus, the global performance of the Machine Learning techniques applied for automatic PPR detection. K-Nearest Neighbors and a One-Hidden-Dense-Layer Neural Network were employed to evaluate the performance of this DA stage. The results showed that DA is able to improve the models, making them more robust and more able to generalize. A comparison with the results obtained from a previous experiment also showed a performance improvement of around 20% for the Accuracy and Specificity measurements without Sensitivity suffering any losses. This project is currently being carried out with subjects at Burgos University Hospital, Spain.
Subject(s)
Body Fluids , Electroencephalography , Humans , Brain , Cluster Analysis , HospitalsABSTRACT
Current solid-state thermoelectric converters have poor performance, which typically renders them useless for practical applications. This problem is evidenced by the small figures of merit of typical thermoelectric materials, which tend to be much smaller than 1. Increasing this parameter is then key for the development of functional devices in technologically viable applications that can work optimally. We propose here a feasible and effective design of new thermoelectric systems based on physical gaps in nanoscale junctions. We show that, depending on the type of features, i.e., the character of surface/edge states, on both sides of the gap, it is possible to achieve high figures of merit. In particular, we show that, for configurations that have localized states at the surfaces/edges, which translate into sharp resonances in the transmission, it is possible to achieve large Seebeck coefficients and figures of merit by carefully tuning their energy and their coupling to other states. We calculate the thermoelectric coefficients as a function of different parameters and find non-obvious behaviors, such as the existence of a certain coupling between the localized and bulk states for which these quantities have a maximum. The highest Seebeck coefficients and figures of merit are achieved for symmetric junctions, which have the same coupling between the localized state and the bulk states on both sides of the gap. The features and trends of the thermoelectric properties and their changes with various parameters that we find here can be applied not only to systems with nanogaps but also to many other nanoscale junctions, such as those that have surface states or states localized near the contacts between the nanoscale object and the electrodes. The model presented here can, therefore, be used to characterize and predict the thermoelectric properties of many different nanoscale junctions and can also serve as a guide for studying other systems. These results pave the way for the design and fabrication of stable next-generation thermoelectric devices with robust features and improved performance.
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BACKGROUND: Patients discovered recumbent, helpless and incapacitated, awake or unresponsive are referred to as "long lie trauma" (LLT) in the German medical jargon. Yet, a characterization of this cohort is missing. METHODS: We retrospectively analyzed all LLT patients admitted to the emergency department of the University Hospital Cologne from July 2018 to December 2020. RESULTS: A total of 50 LLT patients (median age 76 years, median time on the ground 13.5â¯h) were identified. The FD was most often attributed to primary cerebral causes in 40% of the cases (20% ischemic stroke, 16% intracranial hemorrhage, 4% epilepsy), intoxication/overdose (12%), and trauma (10%). It was often associated with infection (52%), injury (22%), hypovolemia (66%), acute kidney injury (20%), and severe rhabdomyolysis (creatine kinaseâ¯≥ 5000â¯U/l, 21%) as well as severe hypothermia <â¯32⯰C (20%). Overall, 69% of the patients were admitted to an intensive care unit and in-hospital mortality was 50%. CONCLUSION: The term "long lie trauma" describes a complex clinical situation, in which various conditions lead to an incapacitated state with acute onset, which then causes further adverse health effects. Trauma or tissue damage were no obligatory requirement in this syndrome. Considering the high morbidity and in-hospital mortality, patients should initially be treated in the emergency room by an interdisciplinary team.
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Acute Kidney Injury , Emergency Service, Hospital , Humans , Aged , Retrospective Studies , Intensive Care Units , HospitalsABSTRACT
The aim of this research was to evaluate the physiological and behavioural parameters in Saanen goat kids treated with flunixin meglumine compared with no analgesic treatment after cautery disbudding using a device fueled by propane gas. At 7 days of age, 30 goat kids were randomly allocated to three groups: Sham (Sh) control, (i.e., simulating disbudding); Disbudding (Di), using thermal cauterization; Disbudding + Flunixin (DiFl), thermal cauterization + flunixin meglumine (2.2 mg/kg body weight, 15 min before treatment). Each kid was video-recorded for 30 min before and after treatment to evaluate the frequency of head shaking, head scratching, body shaking, grooming, head rubbing, jumping, running, and bleating. Blood samples were taken 30 min after disbudding to evaluate serum cortisol concentrations and white blood cell count. Heart rate (HR) and respiratory rate (RR) were measured using a stethoscope. Liveweight of goat kids was recorded at birth, -24 h and 7 days after treatment, and at 25 days of age. The mean frequency of head shaking and head scratching was higher (p = 0.0001) after disbudding in Di (37.5 ± 47.8 and 33.32 ± 31.2) group compared to Sh (3.42 ± 3.58 and 2.2 ± 1.8) and DiFl, (4.02 ± 2.76 and 4.42 ± 3.72) groups. The frequency of jumping was higher (p = 0.022) for Di (3.74 ± 2.24) than that of DiFl (0.39 ± 0.92). The remaining behaviours did not show differences (p > 0.05). HR and RR were higher (HR: p < 0.0048; RR: p < 0.035) in group Di (HR: 156 ± 13.6; RR: 66 ± 14.8) than in Sh (HR: 138 ± 8.48; RR: 55.6 ± 5.4) and in DiFl (HR: 136 ± 6.38; RR: 52.8 ± 4.13). No differences were detected between live weight, serum cortisol and white blood cell count data (p > 0.05). Results show that flunixin meglumine was effective at reducing pain-related behaviours when given at the time of disbudding.
Subject(s)
Hydrocortisone , Pain , Animals , Pain/drug therapy , Pain/etiology , Pain/veterinary , Cautery/veterinary , GoatsABSTRACT
INTRODUCTION: Mexico is one of the countries that is most affected by mortality due to COVID-19. Once infected, the indigenous population living in the lower-income states had worse outcomes. Our objectives were to analyze outcomes by ethnic group, and determine the association between state-level income and the incidence, hospitalizations, outpatients, and death rates per 100,000 population. METHODOLOGY: We analyzed 1,037,567 confirmed COVID-positive cases from February 29 to November 13, 2020 recorded in the Mexican COVID-19 cases database. Sociodemographic characteristics, comorbidities, and outcomes were analyzed. Data was allocated according to the state where the patients were treated. Statistical association between age-adjusted incidence and death rates with state-level GDP per capita (as a measure of income), were ascertained using Spearman correlations. Kruskal-Wallis tests examine the association of cumulative incidence, hospitalizations, outpatients, and death rates, with income quartiles. When significant, a follow-up analysis (Mann-Whitney) was conducted. RESULTS: Respective cumulative incidence rates and death rates were: 900.3 (non-indigenous) and 94.4 (indigenous), and 87.1 (non-indigenous) and 13.9 (indigenous). Spearman correlation coefficients of income with age-standardized incidence and death rates were 0.657 and 0.607 (p < 0.001 for both). Kruskal-Wallis H-Values indicate significant median differences by income in total population rates: cumulative incidence 13.47 (p < 0.01), hospitalizations 11.67 (p < 0.01), outpatients 12.86 (p < 0.01), and deaths 8.92 (p < 0.05). CONCLUSIONS: Cumulative incidence, hospitalizations, outpatients, and mortality rates presented a reversed socioeconomic status health gradient in Mexico. Less adverse outcomes were observed in the lowest-income states compared to higher-income states.
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COVID-19 , COVID-19/epidemiology , Ethnicity , Hospitalization , Humans , Income , Mexico/epidemiology , OutpatientsABSTRACT
AIM OF THE STUDY: Description and comparison of cohort characteristics and outcome of adult patients with out-of-hospital cardiac arrest (OHCA) attributed to poisoning (P-OHCA) versus patients with OHCA attributed to other medical causes (NP-OHCA). METHODS: We included all patients who received cardiopulmonary resuscitation after OHCA between January 2011 and December 2020 from German emergency medical services with good data quality in the German Resuscitation Registry. EXCLUSION CRITERIA: patients < 18 years of age or OHCA attributed to trauma, drowning, intracranial bleeding or exsanguination. RESULTS: Patients with P-OHCA (n = 574) were significantly younger compared to NP-OHCA (n = 40,146) (median age of 43 (35-54) years vs. 73 (62-82) years; p < 0.001). Cardiac arrest in P-OHCA patients was significantly less often witnessed by bystanders (41.8 % vs. 66.2 %, p < 0.001). Asystole was the predominant initial rhythm in P-OHCA patients (73.5% vs. 53.7%, p < 0.001) while ventricular fibrillation (VF) and pulseless electrical activity (PEA) were less common (9.2% vs. 25.1% and 16.2 % vs. 20.5%, p < 0.001). P-OHCA had a higher chance of survival with good neurological outcome at hospital discharge (15.2 vs. 8.8 % p < 0.001) and poisoning was an independent protective prognostic factor in multivariate analysis (OR 2.47, 95%-CI [1.71-3.57]). P-OHCA patients with initial PEA survival with good neurological outcome was comparable to initial VF (34.3 % vs. 37.7%). CONCLUSION: Patients in the P-OHCA group had a significantly higher chance of survival with good neurological outcome and PEA as initial rhythm was as favourable as initial VF. Therefore, in P-OHCA patients resuscitation efforts should be extended.
Subject(s)
Cardiopulmonary Resuscitation , Emergency Medical Services , Out-of-Hospital Cardiac Arrest , Adult , Humans , Middle Aged , Out-of-Hospital Cardiac Arrest/etiology , Out-of-Hospital Cardiac Arrest/therapy , Registries , Ventricular FibrillationABSTRACT
HISTORY: We report the case of a young patient who presented to our emergency department with reduced general condition, anemia, and crampy abdominal pain. A previous inpatient workup including abdominal imaging and bone marrow aspiration had not yielded a diagnosis. On inquiry, the patient reported oral ingestion of an Ayurvedic remedy over the course of one month. FINDINGS: 24-year-old circulatory stable patient in reduced general condition with gray skin coloration and a dark gingival margin. Laboratory testing revealed an increase in transaminases and normocytic anemia. A peripheral blood smear showed basophilic stippling of the erythrocytes. Significantly elevated lead levels were detected in the patient's blood and hair. Toxic lead levels were detected in the ingested preparation. DIAGNOSIS: Severe lead poisoning caused by self-medication with an Ayurvedic remedy. Analysis revealed a daily oral lead load of 136 times the maximum permissible dose. THERAPY AND COURSE: By means of chelation therapy, the blood lead levels were significantly reduced, and there was a complete regression of the complaints as well as a normalization of the laboratory findings. CONCLUSION: Lead has toxic effects on all organ systems of the body and is stored in the bone for decades. Symptoms of poisoning are nonspecific; a thorough history and generous indication for measuring lead levels are helpful for the diagnosis.
Subject(s)
Anemia , Lead Poisoning , Anemia/diagnosis , Child, Preschool , Erythrocytes , Humans , Lead/therapeutic use , Lead/toxicity , Lead Poisoning/diagnosis , Lead Poisoning/drug therapy , Lead Poisoning/etiology , Medicine, Ayurvedic/adverse effectsABSTRACT
The aims were to study the epidemiology and the effect of gastrointestinal nematodes (GINs) on yearling cattle in a semiarid region in Argentina and to evaluate the mineral serum levels. Ten- to twelve-month-old calves were monitored between November and April 2019. Animals were divided into three groups: untreated control (CONG; n = 20); group treated with moxidectin (MXD, 200 µg/kg) every 30-40 days (MXDG; n = 20); group equally MXD treated and mineral supplementation administered in November and January (MMG; n = 20). Individual GIN egg counts (epg) and fecal cultures were made every 30-40 days. Animal live weight gain was determined. On 7-11-18, 25-1-19, and 3-4-19, serum levels of Se, Cu, Zn, Mg, and Ca were determined by atom absorption spectrophotometry. At the start of the trial, epg values were low (xÌ = 5.5), which increased only in CONG towards the end of the assay (xÌ = 229). In both GMXD and MMG, epg remained very low (xÌ = 4.1). Cooperia spp. (81%) prevailed over Haemonchus spp. (9%) and Oesophagostomum spp. (9%). Deficiency of Se ranged between marginal and important, except for MMG, although mean values were always below normal. Cu was marginally deficient in CONG and MXDG on the first two sampling dates, whereas MMG had normal values after treatment. Mg had low values in the three groups (xÌ = 1.5 mg/dl), whereas Ca and Zn exhibited normal values. Live weight gain (LWG) was higher in MMG than in MXDG, with significant differences (p < 0.05) by mid-January and then, when epg increased, dewormed groups showed higher LWG (p < 0.034) than CONG. A negative effect of GINs on LWG was observed, as well as low to marginal levels of Se, Cu, and Mg.
Subject(s)
Cattle Diseases , Nematoda , Nematode Infections , Animals , Argentina/epidemiology , Cattle , Cattle Diseases/epidemiology , Feces , Gastrointestinal Tract , Nematode Infections/epidemiology , Nematode Infections/veterinary , Parasite Egg Count/veterinaryABSTRACT
Compton imaging represents a promising technique for range verification in proton therapy treatments. In this work, we report on the advantageous aspects of the i-TED detector for proton-range monitoring, based on the results of the first Monte Carlo study of its applicability to this field. i-TED is an array of Compton cameras, that have been specifically designed for neutron-capture nuclear physics experiments, which are characterized by [Formula: see text]-ray energies spanning up to 5-6 MeV, rather low [Formula: see text]-ray emission yields and very intense neutron induced [Formula: see text]-ray backgrounds. Our developments to cope with these three aspects are concomitant with those required in the field of hadron therapy, especially in terms of high efficiency for real-time monitoring, low sensitivity to neutron backgrounds and reliable performance at the high [Formula: see text]-ray energies. We find that signal-to-background ratios can be appreciably improved with i-TED thanks to its light-weight design and the low neutron-capture cross sections of its LaCl[Formula: see text] crystals, when compared to other similar systems based on LYSO, CdZnTe or LaBr[Formula: see text]. Its high time-resolution (CRT [Formula: see text] 500 ps) represents an additional advantage for background suppression when operated in pulsed HT mode. Each i-TED Compton module features two detection planes of very large LaCl[Formula: see text] monolithic crystals, thereby achieving a high efficiency in coincidence of 0.2% for a point-like 1 MeV [Formula: see text]-ray source at 5 cm distance. This leads to sufficient statistics for reliable image reconstruction with an array of four i-TED detectors assuming clinical intensities of 10[Formula: see text] protons per treatment point. The use of a two-plane design instead of three-planes has been preferred owing to the higher attainable efficiency for double time-coincidences than for threefold events. The loss of full-energy events for high energy [Formula: see text]-rays is compensated by means of machine-learning based algorithms, which allow one to enhance the signal-to-total ratio up to a factor of 2.