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Abstract Background Musculoskeletal disorders are common in the active military and are associated with significant lost duty days and disability. Implementing programs of care to manage musculoskeletal disorders can be challenging in complex healthcare systems such as in the military. Understanding how programs of care for musculoskeletal disorders have been implemented in the military and how they impact outcomes may help to inform future implementation interventions in this population. Methods We conducted a scoping review using the modified Arksey and O’Malley framework to identify literature on (1) implementation interventions of musculoskeletal programs of care in the active military, (2) barriers and facilitators of implementation, and (3) implementation outcomes. We identified studies published in English by searching MEDLINE, CINAHL, Embase, and CENTRAL (Cochrane) from inception to 1 June 2018 and hand searched reference lists of relevant studies. We included empirical studies. We synthesized study results according to three taxonomies: the Effective Practice and Organization of Care (EPOC) taxonomy to classify the implementation interventions; the capability, opportunity, motivation-behavior (COM-B) system to classify barriers and facilitators of implementation; and Proctor et al.’s taxonomy (Adm Policy Ment Health 38:65–76, 2011) to classify outcomes in implementation research. Results We identified 1785 studies and 16 were relevant. All but two of the relevant studies were conducted in the USA. Implementation interventions were primarily associated with delivery arrangements (e.g., multidisciplinary care). Most barriers or facilitators of implementation were environmental (physical or social). Service and client outcomes indicated improved efficiency of clinical care and improved function and symptomology. Studies reporting implementation outcomes indicated the programs were acceptable, appropriate, feasible, or sustainable. Conclusion Identification of evidence-based approaches for the management of musculoskeletal disorders is a priority for active-duty military. Our findings can be used by military health services to inform implementation strategies for musculoskeletal programs of care. Further research is needed to better understand (1) the components of implementation interventions, (2) how to overcome barriers to implementation, and (3) how to measure implementation outcomes to improve quality of care and recovery from musculoskeletal disorders.

Abstract Background Musculoskeletal injuries are one of the most prevalent battle and non-battle related injuries in the active duty military. In some countries, chiropractic services are accessed to manage such injuries within and outside military healthcare systems; however, there is no recent description of such access nor outcomes. This scoping review aimed to synthesize published literature exploring the nature, models, and outcomes of chiropractic services provided to active duty military globally. Method We employed scoping review methodology. Systematic searches of relevant databases, including military collections and hand searches were conducted from inception to October 22, 2018. We included peer-reviewed English literature with qualitative and quantitative designs, describing chiropractic practice and services delivered to active duty military worldwide. Paired reviewers independently reviewed all citations and articles using a two-phase screening process. Data from relevant articles were extracted into evidence tables and sorted by study type. Results were descriptively analyzed. Results We screened 497 articles and 20 met inclusion criteria. Chiropractic services were commonly provided on-base only in the US. Services were accessed by physician referral and commonly after initiation or non-response to other care. Use of scope of practice was determined by the system/facility, varying from intervention specific to comprehensive services. Back pain with and without radiculopathy accounted for most complaints. Treatment outcomes were reported primarily by case reports. However, two recent randomized trials reported improved pain, disability, and satisfaction when adding chiropractic care to usual medical care compared to usual medical care alone in management of low back pain. Specific reaction time measures in special operation forces military did not improve after chiropractic care compared to wait-list control. Conclusions Our scoping review found the majority of published articles described chiropractic services in the active duty military in the US setting. Recent RCTs suggest a benefit of including chiropractic care to usual medical care in managing back pain in active duty military. Yet despite reported benefits in Australia, Canada, and the US, there is a need for further qualitative, descriptive, and clinical trial data worldwide to inform the role of chiropractic services in active duty military.

Abstract Background Neoantigens that arise as a consequence of tumor-specific mutations can be recognized by T lymphocytes leading to effective immune surveillance. In colorectal cancer (CRC) and other tumor types, a high number of neoantigens is associated with patient response to immune therapies. The molecular processes governing the generation of neoantigens and their turnover in cancer cells are poorly understood. We exploited CRC as a model system to understand how alterations in DNA repair pathways modulate neoantigen profiles over time. Methods We performed whole exome sequencing (WES) and RNA sequencing (RNAseq) in CRC cell lines, in vitro and in vivo, and in CRC patient-derived xenografts (PDXs) to track longitudinally genomic profiles, clonal evolution, mutational signatures, and predicted neoantigens. Results The majority of CRC models showed remarkably stable mutational and neoantigen profiles; however, those carrying defects in DNA repair genes continuously diversified. Rapidly evolving and evolutionary stable CRCs displayed characteristic genomic signatures and transcriptional profiles. Downregulation of molecules implicated in antigen presentation occurred selectively in highly mutated and rapidly evolving CRC. Conclusions These results indicate that CRCs carrying alterations in DNA repair pathways display dynamic neoantigen patterns that fluctuate over time. We define CRC subsets characterized by slow and fast evolvability and link this phenotype to downregulation of antigen-presenting cellular mechanisms. Longitudinal monitoring of the neoantigen landscape could be relevant in the context of precision medicine.

This paper proposes a deep leaning technique for accurate detection and reliable classification of organic pollutants in water. The pollutants are detected by means of cyclic voltammetry characterizations made by using low-cost disposable screen-printed electrodes. The paper demonstrates the possibility of strongly improving the detection of such platforms by modifying them with nanomaterials. The classification is addressed by using a deep learning approach with convolutional neural networks. To this end, the results of the voltammetry analysis are transformed into equivalent RGB images by means of Gramian angular field transformations. The proposed technique is applied to the detection and classification of hydroquinone and benzoquinone, which are particularly challenging since these two pollutants have a similar electroactivity and thus the voltammetry curves exhibit overlapping peaks. The modification of electrodes by carbon nanotubes improves the sensitivity of a factor of about ×25, whereas the convolution neural network after Gramian transformation correctly classifies 100% of the experiments.

Biochar is a pyrolytic material with several environmental benefits such as reducing greenhouse gas emissions, sequestering atmospheric carbon and contrasting global warming. However, nowadays, it has moved to the forefront for its conductivity and electron transfer properties, finding applications in the fabrication of electrochemical platforms. In this field, researchers have focused on low-cost biomass capable of replacing more popular and expensive carbonaceous nanomaterials (i.e., graphene, nanotubes and quantum dots) in the realization of sensitive cost-effectiveness and eco-friendly electrochemical tools. This review discusses recent developments of biochar-modified screen-printed electrodes (SPEs). Special attention has been paid to biochar’s manufacturing processes, electron-donating capabilities and sensing applications. Examples of representative works are introduced to explain the distinct roles of biochar in several electro-bioanalytical strategies.

About 10–20% of breast/ovarian (BC/OC) cancer patients undergoing germline BRCA1/2 genetic testing have been shown to harbor Variants of Uncertain Significance (VUSs). Since little is known about the prevalence of germline BRCA1/2 VUS in Southern Italy, our study aimed at describing the spectrum of these variants detected in BC/OC patients in order to improve the identification of potentially high-risk BRCA variants helpful in patient clinical management. Eight hundred and seventy-four BC or OC patients, enrolled from October 2016 to December 2020 at the “Sicilian Regional Center for the Prevention, Diagnosis and Treatment of Rare and Heredo-Familial Tumors” of University Hospital Policlinico “P. Giaccone” of Palermo, were genetically tested for germline BRCA1/2 variants through Next-Generation Sequencing analysis. The mutational screening showed that 639 (73.1%) out of 874 patients were BRCA-w.t., whereas 67 (7.7%) were carriers of germline BRCA1/2 VUSs, and 168 (19.2%) harbored germline BRCA1/2 pathogenic/likely pathogenic variants. Our analysis revealed the presence of 59 different VUSs detected in 67 patients, 46 of which were affected by BC and 21 by OC. Twenty-one (35.6%) out of 59 variants were located on BRCA1 gene, whereas 38 (64.4%) on BRCA2. We detected six alterations in BRCA1 and two in BRCA2 with unclear interpretation of clinical significance. Familial anamnesis of a patient harboring the BRCA1-c.3367G>T suggests for this variant a potential of pathogenicity, therefore it should be carefully investigated. Understanding clinical significance of germline BRCA1/2 VUS could improve, in future, the identification of potentially high-risk variants useful for clinical management of BC or OC patients and family members.

Abstract Oxygen support with high‐flow nasal cannula (HFNC) is gentler than mechanical ventilation and may provide significant benefits, but more studies are needed to investigate the efficacy and safety of different respiratory supports in patients with COVID‐19 pneumonia.

A novel flow injection microfluidic immunoassay system for continuous monitoring of saxitoxin, a lethal biotoxin, in seawater samples is presented in this article. The system consists of a preimmobilized G protein immunoaffinity column connected in line with a lab-on-chip setup. The detection of saxitoxin in seawater was carried out in two steps: an offline incubation step (competition reaction) performed between the analyte of interest (saxitoxin or Ag, as standard or seawater sample) and a tracer (an enzyme-conjugated antigen or Ag*) toward a specific polyclonal antibody. Then, the mixture was injected through a “loop” of a few μL using a six-way injection valve into a bioreactor, in line with the valve. The bioreactor consisted of a small glass column, manually filled with resin upon which G protein has been immobilized. When the mixture flowed through the bioreactor, all the antibody-antigen complex, formed during the competition step, is retained by the G protein. The tracer molecules that do not interact with the capture antibody and protein G are eluted out of the column, collected, and mixed with an enzymatic substrate directly within the microfluidic chip, via the use of two peristaltic pumps. When Ag* was present, a color change (absorbance variation, ΔAbs) of the solution is detected at a fixed wavelength (655 nm) by an optical chip docking system and registered by a computer. The amount of saxitoxin, present in the sample (or standard), that generates the variation of the intensity of the color, will be directly proportional to the concentration of the analyte in the analyzed solution. Indeed, the absorbance response increased proportionally to the enzymatic product and to the concentration of saxitoxin in the range of 3.5 × 10–7–2 × 10–5 ng ml−1 with a detection limit of 1 × 10–7 ng ml−1 (RSD% 15, S N−1 equal to 3). The immunoanalytical system has been characterized, optimized, and tested with seawater samples. This analytical approach, combined with the transportable and small-sized instrumentation, allows for easy in situ monitoring of marine water contaminations.

Water pollution is nowadays a global problem and the effective detection of pollutants is of fundamental importance. Herein, a facile, efficient, robust, and rapid (response time < 2 min) method for the determination of important quinone-based industrial pollutants such as hydroquinone and benzoquinone is reported. The recognition method is based on the use of screen-printed electrodes as sensing platforms, enhanced with carbon-based nanomaterials. The enhancement is achieved by modifying the working electrode of such platforms through highly sensitive membranes made of Single- or Multi-Walled Carbon Nanotubes (SWNTs and MWNTs) or by graphene nanoplatelets. The modified sensing platforms are first carefully morphologically and electrochemically characterized, whereupon they are tested in the detection of different pollutants (i.e., hydroquinone and benzoquinone) in water solution, by using both cyclic and square-wave voltammetry. In particular, the sensors based on film-deposited nanomaterials show good sensitivity with a limit of detection in the nanomolar range (0.04 and 0.07 μM for SWNT- and MWNT-modified SPEs, respectively) and a linear working range of 10 to 1000 ppb under optimal conditions. The results highlight the improved performance of these novel sensing platforms and the large-scale applicability of this method for other analytes (i.e., toxins, pollutants).

Screen-printed electrodes are the most recent generation of low-cost, mass-produced, sensitive and portable devices for the measurement of analytes of interest. The responses of these platforms, in terms of current intensity and reproducibility, are strongly influenced by factors such as printing procedures, type of ink, substrates, etc. In this paper, an improved inverse-designed screen-printed electrode (IDSPE) is proposed. The electrochemical performance is compared with that obtained using classical screen printed electrodes (SEPs), showing enhanced sensitivity and signal-to-noise ratio (background current minimization 32 ± 3nA and 0.64 ± 0.01nA, for SPE and IDSPE, respectively). A full comparison between inverse and classical screen-printed electrodes is carried out using various electroactive species (potassium ferricyanide, ascorbic acid, hexaammineruthenium(III) chloride and NADH) and two different electrochemical techniques (cyclic and square-wave voltammetry). In tests conducted with potassium ferricyanide the sensitivity of the IDSPE shows a nearly four-fold improvement, and a limit of detection three times better than the values obtained employing the classical SPE. The reproducibility (RSD%) in tests conducted with ascorbic acid is 6% and 12% for IDSPE and SPE, respectively. Moreover, surface modification of both screen-printed electrodes (SPE and IDSPE) with biochar obtained from recycled brewers waste (Bio-SPEs and Bio-IDSPEs), further improves their electrochemical performance, in terms, for example, of the heterogeneous electron transfer constant (0.0024 and 0.0018 for Bio-SPE and Bio-IDSPE, respectively).

Background: Several available data suggest the association between specific molecular subtypes and BRCA1/2 mutational status. Previous investigations showed the association between BRCA1/2 pathogenic variants (PVs) in specific genomic regions and phenotypic variations of cancer relative risk, while the role of PV type and location in determining the breast cancer (BC) phenotypic features remains still unclear. The aim of this research was to describe the germline BRCA1/2 PVs in triple-negative breast cancer (TNBC) versus luminal-like BC and their potential leverage on BC phenotype. Patients & methods: We retrospectively collected and analyzed all clinical information of 531 patients with BC genetically tested for germline BRCA1/2 PVs by Next-Generation Sequencing analysis at University Hospital Policlinico “P. Giaccone” of Palermo (Sicily) from January 2016 to February 2020. Results: Our results corroborate the evidence that BRCA1 -related tumors often have a profile which resembles the TNBC subtype, whereas BRCA2 -associated tumors have a profile that resembles luminal-like BC, especially the Luminal B subtype. Interestingly, our findings suggest that the PVs identified in TNBC were not largely overlapping with those in luminal-like tumors. Differences in the frequency of two PVs potentially associated with different molecular tumor subtypes were observed. BRCA1 -633delC was detected with relatively higher prevalence in patients with TNBC, whereas BRCA2 -1466delT was found mainly in Luminal B tumors, but in no TNBC patient. Conclusion: Future studies examining the type and location of BRCA1/2 PVs within different molecular subtypes are required to verify our hypothesis and could provide an interesting insight into the complex topic of genotype–phenotype correlations. Additionally, a more in-depth understanding of the potential correlations between BRCA PVs and clinical and phenotypic features of hereditary BC syndrome patients could be the key to develop better strategies of prevention and surveillance in BRCA -positive carriers without disease.

La ciudad en el teatro de Calderón se elabora según procedimientos deícticos que se originan de dos perspectivas epistemológicas que connotan la Weltanschauung de autor constitutiva de su ‘Filosofía de la Historia’. La primera plantea una visión escatológica de toda la historia humana elaborada a partir de la Patrística hasta san Agustín (De civitate Dei). La segunda procede de la cultura humanística renacentista que establece los preceptos del escenario en la base de la distinción de los géneros dramáticos. Sin embargo, la poética del autor a veces construye las dos perspectivas de forma dialéctica, puesto que traza un esbozo de la ciudad que se muestra en su vigencia y en su evolución. Si por una parte a lo largo del eje de la verticalidad de los abismos a los cielos se traza el recorrido de la ‘civitas terrena’ a la ‘civitas Dei’ o, por el contrario, su precipitarse en la ‘civitas infernalis’; por otra, la ciudad en su concreta historia ‘en fieri’ puede ser representada como ‘ciudad ideal’ renacentista o como ciudad terrena. De hecho, con el auxilio de la Gracia, es propio de todos los hombres la facultad de realizar para su propia ciudad la perspectiva del Ἔσχατον.

Introduction Little is known about effective, efficient and acceptable management of back pain in children. A comprehensive and updated evidence synthesis can help to inform clinical practice.Objective To inform clinical practice, we aim to conduct a systematic review of the literature and synthesise the evidence regarding effective, cost–effective and safe rehabilitation interventions for children with back pain to improve their functioning and other health outcomes.Methods and analysis We will search MEDLINE, Embase, PsycINFO, CINAHL, the Index to Chiropractic Literature, the Cochrane Controlled Register of Trials and EconLit for primary studies published from inception in all languages. We will include quantitative studies (randomised controlled trials, cohort and case–control studies), qualitative studies, mixed-methods studies and full economic evaluations. To augment our search of the bibliographic electronic databases, we will search reference lists of included studies and relevant systematic reviews, the WHO International Clinical Trials Registry Platform and consult with content experts. We will assess the risk of bias using appropriate critical appraisal tools. We will extract data about study and participant characteristics, intervention type and comparators, context and setting, outcomes, themes and methodological quality assessment. We will use a sequential approach at the review level to integrate data from the quantitative, qualitative and economic evidence syntheses.Ethics and dissemination Ethics approval is not required. We will disseminate findings through activities, including (1) presentations in national and international conferences; (2) meetings with national and international decision makers; (3) publications in peer-reviewed journals and (4) posts on organisational websites and social media.PROSPERO registration number CRD42019135009.

The worldwide spread of coronavirus disease 2019 (COVID-19), caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a pandemic by the World Health Organization (WHO) in March 2020. According to clinical studies carried out in China and Italy, most patients experience mild or moderate symptoms; about a fifth of subjects develop a severe and critical disease, and may suffer from interstitial pneumonia, possibly associated with acute respiratory distress syndrome (ARDS) and death. In patients who develop respiratory failure, timely conventional oxygen therapy through nasal catheter plays a crucial role, but it can be used only in mild forms. Continuous positive airway pressure (CPAP) support or non-invasive mechanical ventilation (NIV) are uncomfortable, and require significant man–machine cooperation. Herein we describe our experience of five patients with COVID-19, who were treated with high-flow nasal cannula (HFNC) after failure of CPAP or NIV, and discuss the role of HFNC in COVID-19 patients. Our findings suggest that HFNC can be used successfully in selected patients with COVID-19-related ARDS. The reviews of this paper are available via the supplemental material section .

Introduction Surgical rates for low back pain (LBP) have been increasing in Europe, North America and Asia. Many patients treated surgically will require postsurgical rehabilitation. Little is known about the effectiveness of postsurgical rehabilitation interventions on health outcomes or about patients’ experiences with these interventions.Objectives To conduct a mixed studies systematic review of quantitative and qualitative studies regarding: (1) the effectiveness and safety of postsurgical rehabilitation interventions for adults with LBP treated surgically and (2) the experiences of patients, healthcare providers, caregivers or others involved with the rehabilitation.Methods and analysis We will search MEDLINE, Embase, PsycINFO, CINAHL, the Index to Chiropractic Literature, the Cochrane Controlled Register of Trials and the Rehabilitation & Sports Medicine Source for peer-reviewed empirical studies published from inception in any language. Studies using quantitative, qualitative and mixed methodologies will be included. We will also search reference lists of all eligible articles. Data extraction will include type of presurgical pathology, indication for surgery, surgical procedure, how the intervention was delivered and by whom, context and setting. We will conduct a quality assessment of each study and consider study quality in our evidence synthesis. We will use a sequential approach at the review level to synthesise and integrate data. First, we will synthesise the quantitative and qualitative studies independently, conducting a meta-analysis of the quantitative studies if appropriate and thematic synthesis of the qualitative studies. Then, we will integrate the quantitative and qualitative evidence by juxtaposing the findings in a matrix.Ethics and dissemination Ethical approval is not required for this knowledge synthesis. Findings will be disseminated through knowledge translation activities including: (1) presentations at national and international conferences and scientific meetings; (2) presentations to local and international stakeholders; (3) publications in peer-reviewed journals and (4) posts on organisational websites.PROSPERO registration number CRD42019134607.

In this review, photoinduced electron transfer processes in specifically designed assembled architectures have been discussed in the light of recent results reported from our laboratories. A convenient and useful way to study these systems is described to understand the rules that drive a light-induced charge-separated states and its subsequent decay to the ground state, also with the aim of offering a tutorial for young researchers. Assembled systems of covalent or supramolecular nature have been presented, and some functional multicomponent systems for the conversion of light energy into chemical energy have been discussed.

Buprestis (Ancylocheira) dalmatina Mannerheim, 1837, an E-Mediterranean Buprestid species, is here recorded for the first time from southern Italy (forest areas of Matera province, Basilicata Region). The here reported records of B. dalmatina are based on material collected on Pinus halepensis Mill. in re-forested coastal areas; the species is therefore supposed to have been very likely introduced. Some aspects of the ecological relationships of Buprestis dalmatina with the closely related and syntopic Pinus borers B. humeralis, B. novemmaculata and B. haemorrhoidalis haemorrhoidalis in Southern Italy are also briefly discussed.

Uncertainty in rainfall datasets and landslide inventories is known to have negative impacts on the assessment of landslide-triggering thresholds. In this paper, we perform a quantitative analysis of the impacts of uncertain knowledge of landslide initiation instants on the assessment of rainfall intensity–duration landslide early warning thresholds. The analysis is based on a synthetic database of rainfall and landslide information, generated by coupling a stochastic rainfall generator and a physically based hydrological and slope stability model, and is therefore error-free in terms of knowledge of triggering instants. This dataset is then perturbed according to hypothetical reporting scenarios that allow simulation of possible errors in landslide-triggering instants as retrieved from historical archives. The impact of these errors is analysed jointly using different criteria to single out rainfall events from a continuous series and two typical temporal aggregations of rainfall (hourly and daily). The analysis shows that the impacts of the above uncertainty sources can be significant, especially when errors exceed 1 day or the actual instants follow the erroneous ones. Errors generally lead to underestimated thresholds, i.e. lower than those that would be obtained from an error-free dataset. Potentially, the amount of the underestimation can be enough to induce an excessive number of false positives, hence limiting possible landslide mitigation benefits. Moreover, the uncertain knowledge of triggering rainfall limits the possibility to set up links between thresholds and physio-geographical factors.