In the present work, indium tin oxide (ITO)/n‐CdS/p‐SnS/Au structured solar cells are fabricated with best conversion efficiency of 0.005%. A detailed investigation is made into the cause of the poor conversion efficiency and the cause is narrowed down to defects in p‐SnS which effect the junction and the neutral region of the cell. The junctions performance is quantified using the ideality factor which is found to be related to the band misalignment. The paper also investigates into literature and discusses efforts made to overcome the problems with this structure. A solar cell consists of three regions, namely a) the junction region, b) the neutral region, and finally c) the electrodes. A drop in performance of any one of the three regions would result in a substantial drop in the device performance. In our previous report,2−5 Torr. The layers were fabricated one after another as per the schematics shown in FigureJV characteristics were measured using a Keithley's 2400 source meter under standard AM 1.5 spectra.Thin films of CdS and SnS were fabricated in our lab on indium tin oxide (ITO) substrate by thermal evaporation using a Hind Hivac 12AUD) coating unit, in vacuum better than 10AUD coati33.1FigureThe X‐ray diffractogram of CdS film Figure2A showa, b, and c equal to ≈0.3980, ≈0.433, and ≈1.118 nm, respectively. The unit cell consists of tin and sulfur atoms held by covalent bonds arranging themselves in layered structure (referred to as “a–b” plane) with van der Waal forces acting between the layers along the “c”‐axis. The peaks at 2θ ≈ 28° and ≈50° correspond to (102) and (122) orientation of crystal planes, respectively. Both the peaks were found to be shifted from the positions mentioned in the ASTM card, peak corresponding to (102) orientation was right‐shifted while the (122) orientation peak was left‐shifted indicating compressive and tensile stress acting on the two diffracting planes. However, X‐ray diffractogram corresponding to 1175 nm showed a drastic decrease in X‐ray peak intensities. This decrease in XRD peak intensities could be due to the change in crystal orientation or grain morphology in SnS thin films expected in films of this thickness based on our observations reported earlier.Figure 3.2Eg ≈ 2.42 eV which matched those reported in most of the literature.TableE). This results in a decrease in the effective bandgap of the material. ΔE was calculated from the exponential region of the absorption spectra appearing just before the band edge, using the equationThe UV–vis absorption spectra of CdS layer on ITO was used to determine the bandgap of the 365 nm CdS layer, used as the window layer in our ITO/n‐CdS/p‐SnS/Au solar cell structure. Standard Tauc methodE as shown in FigureThe bandgap of p‐SnS absorber layers was found to decrease with increasing Δ3.3FigureJV characteristics of five different solar cells. Each ITO/n‐CdS/p‐SnS/Au structure solar cell had a different thickness of the p‐SnS active layer. The thickness of the p‐SnS layer have been indicated in the figure itself. Immediately one can make out two important features from the JV characteristics. The first significant feature is that the area enclosed by the JV curve in the fourth quadrant is not rectangular in shape but triangular. Such “near‐triangular” area under the curve in the fourth quadrant have also been observed by Li et al.Rsh) or in other words increased leakage current through the solar cells junction.Rsh) and series resistances (Rs) for the five solar cells were calculated from the data of Figure Rs and Rsh were found to be approximately equal and decreasing with increasing SnS layer thickness . This decrease in Rs with increasing film thickness could be well expected from the increasing hole mobility with film thickness of p‐SnS layer as reported in ref. Rsh accounts for the leakage current in the cell. Ideally, the value of Rsh should be infinite indicating that there is no leakage current, however a lowering in Rsh value indicates the presence of a conductive path across the depletion width. This leakage path deprives current from the intended load and hence degrade the cell performance.The shunt  thickness. The trend obtained for efficiency variation with film thickness corroborates our initial result of diffusion length variation of majority carriers with film thickness.μτ product or the diffusion length (L)gure qv:  shows thReddy et al.4.2i) and Cd‐antisites (Cds) gives rise to shallow donor levels in the forbidden bandgap of CdS thin films.Rsh for different cells is due to the varying defect concentration for varying thicknesses of SnS layers in the cells as is evident from different band spreading (or ΔE) observed for the cells  in the positions of conduction band minima (CBM) or valence band maxima (VBM), respectively results in formation of a cliff or a spike structure at the junction, which is determined by solving the Poisson's equation at the junction. These structures arising due to band discontinuity at the junction impedes the carrier transport and hence deteriorates the cell performance. Figure Ec between CdS and SnS layer would lead to formation of cliff structureE, film thickness, etc.) would lead to the shifting of CBM thus increasing the conduction band offset ΔEc and increasing barrier/cliff height, as is clear from the figure. Also, since these structures would hinder the movement of the carriers across the junction, there would be carrier accumulation at the junction which would manifest as large ideality factor for the heterojunction. This would imply that the poor band alignment (Cliff barrier) at the SnS/CdS junction assist the defect states present at the junction and further deteriorate the solar cell performance, possibly by resulting in lower Voc values.Apart from the recombinations due to traps, the band‐misalignment between the junction layers also results in loss of charge carriers at the junction. The offset (Δn) for all the junctions under study. Since the light characteristics of the cells were dominated by the parasitic resistance effect, therefore to quantify the junction behavior “n” was calculated using the dark characteristics of the cell as per the model discussed in our previous work.Figure [qv: 7]) implying an increase in band‐misalignment with increasing bandgap of the SnS absorber layer. The scattering observed in the graph might be present due to different band tailing observed in the samples. To confirm our results that poor performance of CdS/SnS heterojunction is not only due to band misalignment but also due to tunnel assisted recombination taking place in the junction, we have shown the variation in efficiency with dark ideality factor taken from literature for pristine CdS/SnS junction having SnS layer thickness varying from 1 to 1.5 µm as shown in Figure [qv: 8]. The exponentially decreasing efficiency of the cells with increasing ideality factor implies that the SnS defect structure not only affects the solar cells' neutral region properties but also the junction behavior.Hence, to study the overall effect of the junction properties  on solar cell performance, we calculated ideality factor . These cells with gold electrodes gave us the best efficiency. Instead of gold, we tested the same cells with aluminium (Al) electrodes. The Figure [qv: 9]), this would mean an increase in the barrier height at the semiconductor–metal junction for Al electrode as compared to the Au electrode. This in turn would lead to hole accumulation at the semiconductor–metal junction and hence is reflected as an increase in ideality factor. Thus, along with a good p‐SnS/buffer layer junction, p‐SnS/metal contact interface should also be optimized to minimize loss of charge carriers and recombinationsParameters listed in Table Interestingly, Noguchi et al.As a closing note, we would like to add that literature on CdS/SnS solar cells have suggested that a further increase in energy conversion efficiency can be obtained by annealing the cell structure at temperatures as high as 450 °C for long time5J–V curves suggest that the defect structure of p‐SnS thin film effect both of the neutral and junction region properties of the SnS solar cells. For the given structure, maximum efficiency is obtained for the cell with absorber layer thickness of 1068 nm which is closest to the optimized thickness of 900 nm predicted by us based on the diffusion length of the majority carriers. The highest efficiency achieved in the present work is far less than the maximum reported efficiency of ≈0.3% for pristine n‐CdS/p‐SnS heterojunction. In this paper, we have evaluated the role of all the three regions of the ITO/n‐CdS/p‐SnS/Au solar cells, namely the neutral, junction and electrode regions, in cell performance. The poor performance of the cell was due to decreased shunt resistance or increased current leakage in the cell. The native defects of both the junction layers contributed in trap‐assisted tunneling recombination across the junction and hence an increase in leakage current. Also, the band‐alignment between the CdS and SnS layers is not favourable for carrier transport due to presence of large conduction band offset, impeding the flow of charge carriers toward the electrodes.Solar cells with varying p‐SnS absorber layer thicknesses were grown in a super‐state configuration of ITO/n‐CdS/p‐SnS/Au structure. The analysis of The authors declare no conflict of interest.


To assess current knowledge of National Heart, Lung and Blood Institutes (NHLBI) and Thalassemia International Federation (TIF) recommendations, blood banking practices and perceived challenges among transfusion services in the management of patients with haemoglobinopathies.Previous reports have demonstrated variations in transfusion practices for sickle cell disease (SCD) and thalassemia patients. Recently, NHLBI/TIF have provided transfusion recommendations for patients with haemoglobinopathies.A cross‐sectional survey was conducted of transfusion services from the state of Georgia previously identified as having SCD/thalassemia populations. The survey assessed transfusion service practices in pre‐transfusion testing and blood product selection; awareness/implementation of NHLBI/TIF transfusion‐based recommendations and perceived challenges in transfusing haemoglobinopathy patients.Responses were received from 35 of 49 (71%) institutions. Only institutions indicating transfusing SCD or thalassemia patients (32) were included in analysis. Seventy‐one percent of non‐sickle cell treatment centres (SCTCs) and 20% of non‐thalassemia treatment centres follow NHLBI and TIF recommendations to perform a red blood cell phenotype beyond ABO/Rh(D) and provide Rh and Kell prophylactically matched units for SCD and thalassemia patients, respectively. Forty percent of institutions (33% of non‐SCTCs) employ RBC genotyping to evaluate the red cell phenotype for SCD patients. Over 77% of institutions do not utilise a reliable method to identify SCD patients prior to transfusion, such as a required question/answer field on type/screen or crossmatch orders.Many healthcare systems' transfusion practices for haemoglobinopathy patients are discordant with NHLBI/TIF recommendations. Efforts are needed to increase awareness and implementation of current recommendations among all transfusion services seeing these patients. Red blood cell (RBC) transfusions are a key component of the comprehensive management of patients with sickle cell disease (SCD) and thalassemia; however, they are not devoid of risk. Advances in transfusion practices and clinical care have led to improved safety of transfusion therapy for patients with haemoglobinopathies with regard to transmission of blood‐borne infectious agents, RBC alloimmunisation, transfusional iron overload and suspected transfusion reactions. However, transfusion practices vary among providers and transfusion services for these patients.et al.,et al.,et al.,et al.  and the Thalassemia International Federation (TIF) published expert panel recommendations for SCD and guidelines for transfusion dependent thalassemia (TDT), respectively, in 2014. These include comprehensive recommendations for transfusion therapy in patients with SCD and TDT, and advocate for all such patients to receive prophylactic Rh ‐matched and Kell‐matched RBCs to reduce the risk of alloimmunisation  cooperative agreement (DD14‐1406) to reduce transfusion‐related complications for people with haemoglobin disorders. It was approved by Georgia State University's institutional review board.et al.,The study targeted hospital blood bank medical directors, laboratory managers, supervisors and medical technicians at institutions where Georgia residents with haemoglobinopathies might seek treatment. Participants were solely recruited at an annual regional meeting of Southeastern Area Blood Bankers (SEABB), with additional, targeted, telephone recruitment to reach Georgia hospitals that collectively provided 90% of all SCD/thalassemia transfusions in the years 2004 through 2008, as identified through prior surveillance (Hulihan Institutions were classified as ‘Sickle Cell Treatment Centers (SCTCs)’ based on being either an NHLBI historically designated Comprehensive Sickle Cell Centre, or currently receiving state funding for comprehensive sickle cell services including newborn screening follow up. Additionally, institutions were classified as ‘Thalassemia Treatment Centers (TTCs)’ based on being previously funded by CDC as part of the Thalassemia Clinical Research Network.A team that included experts in paediatric  and adult (J. R. E.) haematology, transfusion medicine  and qualitative research (J. B.) developed the questions and designed the survey for the web‐based software . The instrument was pilot‐tested by other haematologists and blood bank personnel from outside of the study's geographic scope. The instrument is included as a supplemental figure.The survey questions addressed here covered respondent and institution characteristics, and current practices in transfusion to haemoglobinopathy patients. Additional questions on training needs and preferred learning channels are not reported here but were asked to inform follow‐up activities.Results were exported from Qualtrics to Microsoft Excel  for analysis. Descriptive statistics for categorical variables are reported using proportions. Open‐ended text responses were grouped thematically using inductive analysis.A total of 49 institutions were recruited for the survey, with 35 responding (71%). Multiple responses were received from staff at six institutions. In these cases, the response of the most senior or highly trained individual, by self‐report, was retained for this analysis. Three responding institutions reported providing no SCD or TDT transfusions and were also omitted from this analysis. Included institutions represented 23 Georgia counties and 3 neighbouring states . Three institutions were categorised as SCTCs, and one of these also as a TTC. Additional descriptive data for the sample are provided in Table S1, Supporting Information.All institutions reported using blood from external collection facilities. Only one reported on‐site collection of any of the RBC units issued; and those were estimated to constitute less than 10% of all transfused units. Of the 32 institutions reported providing transfusions for SCD patients, 10 (31%) provided manual exchange transfusions and 13 (41%) provided automated RBC exchange transfusions. The major prescribers of RBC transfusion for SCD/TDT patients included adult haematologists/oncologists, internists, hospitalists, paediatric haematologists/oncologists and emergency medicine physicians. Reported frequency of transfusing SCD and TDT patients is shown in Fig. RBC component processing practices for SCD and TDT patients are illustrated in Table Routine blood group antigen phenotyping practices of both SCD and TDT patients varied among non‐SCTCs/non‐TTCs. Although the TTC and two of three SCTCs perform extended phenotyping (beyond ABO/Rh(D), C/c, E/e and K) for non‐alloimmunised TDT and SCD patients, only 10% of non‐TTCs/non‐SCTCs perform upfront extended phenotyping for all TDT/SCD patients. Similarly, the types of RBC products routinely provided to SCD and TDT patients differed among institutions. Prophylactic matching for Rh C/c, E/e and K in addition to ABO/Rh(D) was reported by all SCTCs and TCCs; but only 20 (71%) non‐SCTCs and two (20%) non‐TTCs follow this practice  reported that they do not employ this method to evaluate the red cell phenotype for SCD patients. One of the three SCTCs performs RBC genotyping for all SCD patients, and two SCTCs and nine (33%) non‐SCTCs utilise RBC genotyping on a case by case basis – most commonly for patients with complicated antibody reactivity and/or to determine whether an autoantibody vs an alloantibody is present (e.g. anti‐e in an e+ patient because of an Rh variant haplotype). Other indications included: new SCD patients without appropriate transfusion or antibody history, or if the immunohaematology reference laboratory (IRL) recommends molecular testing based on a complex workup.N = 30, incorporating responses from multiple staff at the same institution) included: obtaining a reliable and complete transfusion and antibody history across multiple hospital systems , lack of standardised procedures for notifying transfusion services that a patient has either SCD or TDT ; a lack of standard policies/procedures  for RBC phenotyping and product matching  and securing appropriately matched RBC units for alloimmunised patients .The main challenges identified in the transfusion management of SCD and TDT patients , 10 (32·3%) institutions indicated they have no routine system in place for identifying SCD patients who may have been transfused elsewhere. Nine (29%) depend on the patients' clinical provider to obtain a transfusion history to identify whether transfusions have occurred at other institutions . If there is a history of multisite transfusions, the provider notifies the transfusion service to contact the institution(s) where the patient was transfused to obtain antibody history prior to cross‐matching units. Fourteen (45·2%) contact the provider who orders a type/cross on a new SCD patient to obtain a transfusion history. A subgroup five (16·1%) institutions stated that their transfusion service contacts the provider ordering a type/cross on a SCD patient based on certain qualifications to obtain an interim transfusion history. These qualifications included if the direct antiglobulin test or antibody screen is positive, or if no RBC phenotype is on file for a given patient.et al.,et al.,et al.,The findings of this survey provide insights into the inconsistencies in transfusion practices of SCD and thalassemia patients in a geographic region densely populated with these patient populations. Similar to previously published reports  to reduce life‐threatening transfusion‐related complications for patients with haemoglobinopathies.Despite prophylactic matching for Rh  and Kell antigens to prevent alloimmunisation, this phenomenon does occur and sometimes results in DHTRs, one of the most life‐threatening consequences of RBC alloimmunisation. This is especially the case with SCD patients because of their potential for bystander haemolysis of the patient's own erythrocytes and exacerbation of other sickle related complications. Whereas non‐SCD patients may have haemolysis of the transfused unit(s), patients with SCD may also have haemolysis of the transfused units in addition to their own endogenous sickle cell erythrocytes resulting in a post‐transfusion haemoglobin level that is significantly lower than the pre‐transfusion haemoglobin level, approximately 1 to 3 weeks after the inciting transfusion , and approximately a third state there is no routine system in place for identifying SCD patients who may have been transfused elsewhere, thereby limiting their ability to prevent DHTRs from occurring.et al.,RH variant. This highlights the blood bank community's increased awareness that despite serologic matching for Rh antigens, SCD patients continue to form antibodies against blood group antigens within the Rh system because of the high prevalence of RH variants in this population , through increased education and training, or centralising their use in resource limited geographic areas. With regard to RBC genotyping, only one institution (a SCTC) reported to perform RBC genotyping to predict a RBC phenotype in all SCD (and TDT) patients; whereas 60% of transfusion services described not using RBC genotyping at all. This is despite the fact that automated DNA extraction and the ability to test large patient groups on high‐throughput molecular platforms are now readily accessible, and there currently is at least one molecular platform that is US food and drug administration approved as ‘test of record’, which means that the RBC phenotype determined by molecular testing does not require confirmation by serologic methods  would result in a transfer to a centre with an apheresis service. This finding highlights the fact that acute erythrocytaphaeresis may be unavailable for many SCD patients with severe life‐threatening sickle‐related complications, and that chronic erythrocytaphaeresis may be under‐utilised as an iron‐sparing transfusion therapy for SCD patients in need of long‐term chronic transfusion therapy, despite considerable data showing its beneficial effects . Furthermore, these responding institutions accounted for 2037 (83%) of the 2458 transfusions given collectively to this population. Geographically, the 25 Georgia counties from which we received responses were distributed across the state, ranging from dense urban areas (metro Atlanta and suburbs) to sparsely populated rural locations . Therefore, despite not having access to non‐responding institutions, we feel that the response sample is a good representation of institutions within Georgia that transfuse patients with haemoglobinopathies.Although the number of responding institutions is relatively small, analysis of hospital discharge statistics from our data use agreement with Georgia Department of Public Health indicates that the Georgia hospitals in the survey that reported transfusing haemoglobinopathy patients represent approximately one‐third of all those that transfused such patients in 2016 , through increased education and training, or centralising their use in resource‐limited geographic areas. In an expanding world of high‐quality, cost‐effective care, future support of transfusion‐based multi‐centre prospective randomised clinical trials along with implementation science research is critically needed to determine and promote the widespread adoption of evidence‐based practices in the transfusion management of patients with haemoglobinopathies.C. D. J. has functioned as a consultant for Octapharma, Immucor and Biomet Zimmer. R. M. F. has served as an advisory board member for Immucor, and gives educational talks for Terumo BCT. All authors have no relevant conflicts of interest.Figure S1. Blood bank survey.Table S1. Response institution and respondent characteristics.Click here for additional data file.


Speaking up is an important communication strategy to prevent patient harm. The aim of this study was to examine speak up‐related behaviour and climate for the first time in psychiatric hospitals. A cross‐sectional survey was conducted among healthcare workers (HCWs) in six psychiatric hospitals with nine sites in Switzerland. Measures assessed speak up‐related behaviour with 11 items organized in three scales . Speak up‐related climate was assessed by 11 items organized in 3 subscales . Statistical analyses included descriptive statistics, reliability, correlations and multiple regression analysis, confirmatory factor analysis, and analysis of variance for comparing mean scores between professional groups. A total of 817 questionnaires were completed (response rate: 23%). In different items, 45%–65% of HCWs reported perceived safety concerns at least once during the past four weeks. Withholding voice was reported by 13–25% of HCWs, and speaking up was reported by 53%–72% of HCWs. Systematic differences in scores were found between professional groups  and hierarchical groups (lower vs higher status). The vignette showed that hierarchical level and perceived risk of harm for the patient were significant predictors for the self‐reported likelihood to speak up. Situations triggering safety concerns occur frequently in psychiatric hospitals. Speaking up and voicing concerns should be further promoted as an important safety measure. A study in psychiatric units from medical centres in the Veterans Health Administration (VHA) hospital system identified a patient safety event in 28% of all discharges reviewed  the frequency of perceived safety concerns (3 items); ii) the frequency of withholding voice, that is NOT speaking up in specific situations (4 items); and iii) the frequency of speaking up (4 items). Response options for the items in these scales are anchored to ‘in the last four weeks’ and include ‘never’ (0 times), ‘rarely’ (1‐2 times), ‘sometimes’ (3‐5 times), ‘often’ (6‐10 times), and ‘very often’ (more than 10 times). Higher mean scale values indicate higher frequencies of past speaking up and withholding voice behaviours, respectively. Speak up‐related climate is assessed by 11 items organized in 3 subscales: i) the psychological safety for speaking up scale (5 items), ii) the encouraging environment for speaking up scale (3 items), and iii) the resignation scale (3 items). The answers are coded in a 7‐point Likert scale from ‘strongly disagree’ to ‘strongly agree’. Higher mean scale scores indicate higher levels of perceived psychological safety at workplace, higher levels of perceiving the workplace as encouraging for speaking up, and higher levels of resignation with speaking up, respectively. Perceived barriers to speaking up are surveyed with one multiple‐choice item asking for the relevance (yes/no) of 6 predefined reasons for inhibiting one’s own speaking up (e.g. presence of patients). Finally, the survey includes a vignette describing a hypothetical situation in which patient safety is jeopardized . Participants are instructed to consider their anticipated likelihood to speak up if they would find themselves in the situation. They are asked to complete four questions addressing realism of the situation, patient harm, discomfort with, and likelihood of speaking up. These questions each used a 1‐ to 7‐response scale with specifically labelled poles.We used the SUPS‐Q survey instrument which was developed for staff working in acute care (somatic) hospitals. Development and psychometric evaluation of the SUPS‐Q are reported elsewhere  to promote speaking up in the participating hospitals prior to the survey. The target population consisted of all HCWs with direct patient contact. HCWs from the target population were identified by local study coordinators. They received an invitation to participate and a link to the online survey by e‐mail. The survey was open for five weeks (Sept – Nov 2018), and depending on each site, one or two reminders were sent during this period. Participation was anonymous and voluntary; the completion of the survey was considered informed consent.et al.,et al.,P < 0.05 was considered statistically significant. All analyses were performed with Stata 13 .Statistical procedures comprised descriptive analyses of items, subscales, and total scores. Missing data were excluded pairwise. Cronbach’s alpha was calculated as a measure of internal consistency of scales with values >0.7 indicating acceptable consistency. In order to assess convergent and divergent validities, correlations between items and scores or rest scores were inspected. A confirmatory factor analysis (CFA) was conducted to test the defined three‐factor structure of the speaking up climate data using maximum likelihood estimation methods. Model fit was tested using CFI , RMSEA (good fit ≤ 0.06), and SRMR (good fit ≤ 0.08)  (BASEC‐Nr. Req‐2018‐00681).n = 3519), 817 individuals completed the questionnaire . Sample characteristics are provided in Table Of invited staff n = 359, 817 inpsych 1.4 meandoc 1.7 meannurs 1.9, P < 0.001), withholding voice , and speaking up . Staff of higher versus lower hierarchical level reported similar frequencies of perceiving concerns , but higher frequencies of speaking up  and lower frequencies of withholding voice .Responses to the three behavioural scales are reported in Table P = 0.0024).Responses to the climate items are reported in Table Perceived barriers to speaking up among nurses, doctors, and psychologists are illustrated in Figure Responses to the vignette are reported in Table P < 0.001) and perceived risk of harm for the patient  were significant predictors for the self‐reported likelihood to speak up.Regression analyses revealed that after adjusting for professional group (non‐significant), hierarchical level . This result indicates that psychologists may need to be more familiar with rules and expectations that apply in a given situation, in order to feel comfortable to speak up when violations of such rules occur. Our study design, however, does not allow us to draw any further conclusions about the nature of concerns and the type of speak up situations for psychologists. Research to date has largely focused on the dynamics between nursing and medical staff, and future studies should consider including other professions with direct patient contact to better understand their role and contributions to safety.et al.,et al.,We also found systematic differences between the scores of HCWs of higher vs lower hierarchical level. Even though they had similar frequencies of perceiving concern, HCWs of lower hierarchical level had lower frequencies of speaking up, higher frequencies of withholding voice, and generally less positive climate scores. These results support previous research which has shown that authority gradients and power dynamics greatly inhibit the decision to speak up (Morrow et al.,et al.,The SUPS‐Q has been validated and successfully used to assess different speak up dimensions in the acute care setting (Richard et al.,Responses to the clinical scenario confirm previous findings stating that personal assessment of harm and hierarchical level is a strong predictor for speaking up (Lyndon et al.,This study has some limitations. The response rate across all participating hospitals was low. We cannot exclude bias, including selection bias in this study. The survey was administered online and invitations were sent by e‐mail, which may to some extent explain the low participation rate. While web‐based surveys present many advantages over traditional paper‐based surveys, it has been well established that response rates for web surveys are lower than for paper (Dykema et al.,The SUPS‐Q was intentionally designed to be short so that it can easily be used as a monitoring instrument by healthcare organizations. Such initial survey results can demonstrate the importance of voicing concerns to increase patient safety and can be used by organizations and teams to discuss frequent safety concerns and appropriate communication strategies, clarify expectations regarding speaking up, and foster a supportive environment for voicing concerns. However, the instrument does not allow us to fully capture the underlying cultural, social and individual factors that inform speaking up behaviour within mental health care. The results from our survey study should thus serve as starting point for further qualitative research aimed at understanding typical situations that require staff to speak up, and to contextualize their decision to voice concerns or to remain silent. Ethnographic observation would also be a valuable approach to study voicing behaviours in complex social environments. However, one major problem with this approach is that withholding voice is a non‐behaviour not easily observable. Descriptive research of the inpatient psychiatric care setting, for example on the nature of interprofessional collaboration within healthcare teams, the different types of mental health services provided, and existing institutional policies regarding voicing concerns, is needed to interpret the findings from the survey in more detail. This type of research would also allow us to determine transferability of our findings to other countries. It is, for example, plausible that the roles and responsibilities of psychologists in psychiatric hospitals vary among the different healthcare systems. National cultures and different norms influence speaking up behaviour, and thus, the frequency of certain behaviours and perceptions may differ between countries (Kobayashi With this study, we demonstrated that speaking up for patient safety is an important topic in the psychiatric healthcare setting. Speaking up to prevent harm to patients should be further promoted in psychiatric clinics as an important safety measure. In order to fully enact their role as advocates for patient safety, nurses should be empowered to voice concerns even in difficult situations. Further research is needed to gain more insights into the complex trade‐offs and considerations that influence decisions to speak up or withholding voice in the psychiatric healthcare setting.Safety concerns, speaking up and withholding voice are commonly reported by staff working in psychiatric hospitals. Adoption of training programmes in assertive communication to the psychiatric setting may support nurses in taking a lead role in developing personal competencies and shaping organizational culture in psychiatric hospitals. The adapted SUPS‐Q‐PSYCH can be used by psychiatric hospitals to systematically assess and monitor important dimensions of speak up and identify areas for improvement.


HIV testing is one of the key strategies in the HIV/AIDS prevention and control programmes. However, studies examining utilization of this service by men in Malawi are limited. The aim of this study was to assess the uptake and determinants of HIV testing among men in Malawi.Secondary data analysis was conducted on cross–sectional household data for 7478 men aged 15 to 54 years drawn from the 2015–16 Malawi Demographic and Health Survey. Descriptive statistics, bivariate and multivariable logistic regression analyses were performed to identify the socio–demographic, behavioral and health service related factors that are associated with HIV testing service utilisation by men in Malawi. All analyses were performed using the complex sample analysis procedure of the Statistical Package for the Social Sciences version 22.0 to account for the multistage sampling used in Demographic Health Survey.Overall, 69.9% of the participants had ever been tested for HIV. The results indicate that age, region of residence, marital status, covered by health insurance, education and age at first sexual debut are significant predictors of HIV testing among men in Malawi. In particular, men who were in the age group 30–39 years , married , those with secondary or above education , and those who had health insurance  were likely to utilise HIV testing service than their counterparts.The findings suggest that HIV testing services and programmes need to target younger unmarried men aged 15–19, men with low level or no education and expand HIV testing services to the central and southern regions of Malawi. Targeting the undiagnosed men living with HIV in a timely manner is a crucial and necessary step not only for achieving the UNAIDS’ 90–90–90 targets but for individuals to benefit from antiretroviral treatment and to sustainably reduce population–level HIV transmission. Malawi is making progress in the fight against HIV: The HIV prevalence for adult population aged 15–49 has declined over the past 5 years, from 10.6% in 2010 to 8.8% in 2016 . In ordeHIV testing is an essential strategy for reducing HIV related morbidity, mortality and may improve patient outcomes –6. The WMalawi has been implementing rapid HIV testing services since early 2000. The services are provided free of charge in public health facilities and some private clinics/hospitals . DespiteSecondary data analysis was conducted on cross–sectional household data drawn from the 2015–16 Malawi Demographic and Health Survey (MDHS) which is the fifth national sample survey that aims to provide current estimates of basic demographic and health indicators at national, regional and district level. The survey was implemented by the National Statistical Office (NSO) in joint collaboration with the Ministry of Health. The International Classification of Functioning, Disability, and Health (ICF) provided technical support for the survey and stakeholders including the government of Malawi, the United States Agency for International Development (USAID), the United Nations Children’s Fund (UNICEF), and others provided financial support. The field work for data collection was carried out between October 2015 and February 2016. Samples were obtained using a multistage stratified sampling strategy in which 24,562 women of reproductive aged 15–49 years and 7478 men aged 15–54 years were interviewed separately. For the purpose of this study, our analyses included data for 7478 men which were collected using the men’s questionnaire. The questionnaire collected different types of information from the respondents on socio–demographic characteristics, sexual behaviour history, HIV/AIDS–related knowledge, and HIV/AIDS–related stigma. The methodology used in the 2015–2016 MDHS has been reported in detail elsewhere [yes or no. The ‘yes’ category included those who had ever tested for HIV at least once in their lifetime prior to this survey and the ‘no’ category included those who had never tested for HIV in their lifetime.The outcome variable for this study was based on a self–reported previous HIV testing status. This was measured by asking the participants this question: ‘Have you ever tested for HIV?’ HIV testing was treated as a binary variable and the responses were coded as The potential covariates of HIV testing were selected based on literature review –21 and cThe 2015–2016 MDHS data collection procedures were approved by the ICF Macro , the Malawi’s National Health Sciences Research Committee (NHSRC) and informed consent was obtained from respondents at the start of the individual interviews [P ≤ 0.25 in bivariate analysis (logistic regression) were entered together into a multiple logistic regression model [P-value < 0.05 was considered statistically significant.Descriptive statistics (frequencies) were calculated to describe the characteristics of men included in this study and the results were presented as proportion (%). The association between each categorical covariate with the outcome variable (HIV testing) was tested by using Pearson chi-square test (χ2). Logistic regression was then used to establish the magnitude and direction of the associations. All variables that were significant at on model . Crude aP < 0.001). However, religion showed a marginal association with HIV testing (P = 0.046).Table Correlates of HIV testing among men in Malawi based on unadjusted and adjusted logistic regression are presented in Table The study findings demonstrate that over two–third (69.9%) of men in Malawi had been tested for HIV. The results highlight that several socio–demographic, behavioral and health service related factors influence the uptake of HIV testing services among men in Malawi. In particular, participants’ age was an important factor associated with HIV testing in this study. Men who were aged 20 years or older were more likely to have had HIV testing compared to adolescent men (15–19 years). This finding is in accordance with a recent study in Haiti which revealed that older men were more likely to have been tested for HIV than men aged 15 to 19 years . SimilarThe present study demonstrated that having higher educational level was associated with ever being tested for HIV. Educated men might have higher levels of exposure to HIV/AIDS–related information, better knowledge of the advantages of HIV testing as well as ability to make good decision to go for HIV testing than their uneducated counterparts. Other studies conducted elsewhere have also shown that having higher educational status was associated with ever being tested for HIV , 27, 28.Region of residence was also associated with ever being tested for HIV even after adjusting for other variables. We observed that men residing in central and southern region were less likely to test for HIV than those from northern region. Similar findings have also been reported in other studies conducted in Ethiopia and Mozambique, where regional variations in uptake of HIV testing was observed , 29. CulThe results further indicate that HIV testing among men was positively associated with marital status. Men who were married and formerly married were more likely to have been tested for HIV than men who were never married. The possible explanation for this association is that the ministry of health in Malawi encourages male involvement in reproductive health and other care services. As a result, men may have opportunity of being tested for HIV because of frequent interaction with the health care providers when they accompany their partners to the clinic than their unmarried counterparts. Moreover, men are also likely to undergo for HIV testing when they are planning for marriage to know their HIV sero–status than those who have never been married. This result is consistent with the findings of previous studies conducted in Kenya and Mozambique , 30.This study revealed that being covered by health insurance was associated with increased likelihood of HIV testing among Men in Malawi. This finding concurs with the results of a previous study in Haiti which reported that men who had health insurance were likely to have been tested for HIV compared to those who had no health insurance . The mosWhile the body of existing evidence suggests that key socio–demographic factors such as wealth index, area of residence and religion are associated with HIV testing , 31, 32,It is imperative that our results be interpreted under a set of limitations. First, the study was limited to only the variables collected in the MDHS. As such, other important variables  that may affect HIV testing but were not available in MDHS could not be examined. Second, the cross-sectional nature of MDHS limits the capacity to draw any causal inferences. Third, assessment of the outcome variable and some of the covariates was based on self-reported, thereby potentially introducing social desirability bias in participants’ responses. Furthermore, the present study assessed the lifetime occurrence of HIV testing by the participants. It did not focus on recent HIV test seeking behaviour . It is therefore possible that HIV testing happened before the exposure status. Finally, the outcome measure ‘ever been tested for HIV’, while being useful indicator to assess the overall uptake of HIV testing services, does not assess whether the participants who took HIV test received the results of their test or not. Taking an HIV test without knowing the ‘results of the test’ might not have implication for HIV prevention. Further research is needed to complement the findings of the current study by addressing the above limitations.Despite these limitations, this study is the first to analyze the correlates of HIV testing among men in Malawi using a nationally representative sample. Given the representativeness of our sample, the current findings are generalizable to the entire country.This paper provides nationally representative statistics related to HIV testing among men aged 15–54 years in Malawi. The findings suggest the need for health policy makers as well as other stakeholders to sustain current efforts to target younger unmarried men aged 15–19, men with low level or no education and expand HIV testing services to the central and southern regions of Malawi. Targeting the undiagnosed men living with HIV in a timely manner is a crucial and necessary step not only for achieving the UNAIDS’ 90–90-90 targets but for individuals to benefit from antiretroviral treatment and to sustainably reduce population–level HIV transmission.


To evaluate the short‐term cost‐effectiveness of insulin degludec (degludec) vs insulin glargine 100 units/mL (glargine U100) from a Canadian public healthcare payer perspective in patients with type 2 diabetes (T2D) who are at high risk of cardiovascular events and hypoglycaemia.A decision analytic model was developed to estimate costs (2017 Canadian dollars [CAD]) and clinical outcomes  with degludec vs glargine U100 over a 2‐year time horizon. The model captured first major adverse cardiovascular event, death, severe hypoglycaemia and insulin dosing. Clinical outcomes were informed by a post hoc subgroup analysis of the DEVOTE trial (NCT01959529), which compared the cardiovascular safety of degludec and glargine U100 in patients with T2D who are at high cardiovascular risk. High hypoglycaemia risk was defined as the top quartile of patients (n = 1887) based on an index of baseline hypoglycaemia risk factors.In patients at high hypoglycaemia risk, degludec was associated with mean cost savings (CAD 129 per patient) relative to glargine U100, driven by a lower incidence of non‐fatal myocardial infarction, non‐fatal stroke and severe hypoglycaemia, which offset the slightly higher cost of treatment with degludec. A reduced risk of cardiovascular death and severe hypoglycaemia resulted in improved effectiveness (+0.0132 QALYs) with degludec relative to glargine U100. In sensitivity analyses, changes to the vast majority of model parameters did not materially affect model outcomes.Over a 2‐year period, degludec improved clinical outcomes at a lower cost as compared to glargine U100 in patients with T2D at high risk of cardiovascular events and hypoglycaemia. Health economic analyses, including CUAs, are an important tool to assist healthcare professionals in deciding how best to allocate resources efficiently between therapy areas and interventions to achieve maximum healthcare gains within a limited budget.Prior to the DEVOTE trial, CEAs of degludec compared with glargine U100 captured the effects of hypoglycaemia rates and insulin dosing over a short‐term (1‐year) time horizon in patients with type 1 (T1D) or type 2 (T2D) diabetes, based on the phase 3 clinical trial programme.The aim of the present post hoc analysis was to evaluate, from a Canadian public healthcare payer perspective, the short‐term cost‐utility of degludec vs glargine U100 in patients with T2D who are at high risk of hypoglycaemia and cardiovascular events.22.1N = 7637) were randomly assigned 1:1 to receive once‐daily degludec (100 units/mL) or glargine U100, in addition to standard care. The primary endpoint in the DEVOTE trial was time to first MACE, a composite of cardiovascular death, non‐fatal myocardial infarction (MI) or non‐fatal stroke. Severe hypoglycaemia was self‐recorded in the DEVOTE trial and was defined according to the American Diabetes Association definition as an event requiring third‐party assistance.The trial design and primary results of the DEVOTE trial have been published previously.The DEVOTE trial was conducted in accordance with the provisions of the Declaration of Helsinki and the International Conference on Harmonisation Good Clinical Practice Guidelines, the DEVOTE protocol was approved by the independent ethics committee or institutional review board at each trial centre and written informed consent was obtained from each patient before any trial‐related activities.2.2A decision analytic model built in Microsoft Excel 2016 was used to evaluate the short‐term cost‐utility of degludec vs glargine U100, informed by data concerning clinical outcomes and baseline characteristics for the DEVOTE subgroup at high risk of hypoglycaemia . The analysis was conducted over a 2‐year time horizon from a Canadian public healthcare payer perspective. Details of the model structure have been published previously, alongside the findings of a short‐term CUA informed by data from the DEVOTE basal‐bolus subgroup.2.3In this analysis, the subgroup at high risk of hypoglycaemia was defined as the top quartile of patients in the DEVOTE trial, based on an index of established risk factors for severe hypoglycaemia at baseline, including age, diabetes duration, HbA1c, sex and insulin regimen. This internal index of high risk of severe hypoglycaemia was estimated using a Cox regression model of time to first event of severe hypoglycaemia for the full DEVOTE trial population Table . At baseAnalyses were conducted to estimate treatment effects (degludec vs glargine U100) in the DEVOTE subgroup at high risk of hypoglycaemia for the following endpoints: time to first MACE, death from other causes, number of severe hypoglycaemic events, insulin dose and change in HbA1c from baseline to the 24‐month visit . The resulting relative rates for MACE, death from other causes and severe hypoglycaemia (hazard or rate ratios) were applied to the event rates (events/patient‐year of observation) observed in the DEVOTE trial in the glargine U100 arm, to derive event rates for input into the model for the degludec arm, if there was a statistically significant difference between treatment arms , based on the observed distribution of MACE components in the corresponding treatment arm in the DEVOTE trial. Adopting a conservative approach, subsequent cardiovascular events after first MACE were not incorporated into the model. Annual survival was estimated using data for cardiovascular death from first MACE and death from other causes, applied in each of the two annual time periods. Events rates for non‐fatal MI, non‐fatal stroke and severe hypoglycaemia were applied to the surviving cohort in the two annual time periods. In the glargine U100 arm, the basal insulin dose was modelled as the arithmetic mean of the start‐ and end‐of‐year glargine U100 basal doses to approximate the area under the curve, adjusted for survival in each annual time period. This was repeated for bolus insulin, but the mean annual bolus dose was estimated by multiplying the proportion of patients receiving bolus insulin at baseline, 12 or 24 months by the mean bolus dose for each time point. In the case of significant differences between treatment arms, the dose ratio (degludec/glargine U100) was applied to the mean annual glargine U100 basal or bolus dose to derive corresponding doses in the degludec arm (Table P = 0.603), as would be expected in a treat‐to‐target trial.HbA1c was not captured in the model as there was no significant difference in change in HbA1c from baseline to 24 months with degludec vs glargine U100 for the DEVOTE subgroup at high risk of hypoglycaemia  using the Health and Personal Care component of the Canadian Consumer Price Index , obviating assumptions regarding the longevity of clinical effects. It is also highly relevant to the healthcare payer, aligning with the short‐term budget considerations commonly involved in healthcare planning.2.5Deterministic sensitivity analyses were conducted to identify key drivers of outcomes in the base case analysis. Annual discount rates of 0%, 3% or 5% were explored, along with variations in cardiovascular costs  or severe hypoglycaemia costs . Additional sensitivity analyses were performed, in which treatment effects  were applied, regardless of whether they were statistically significant or not, and the glargine U100 distribution of individual MACE components was applied to both arms. Alternative disutilities were explored for cardiovascular events and severe hypoglycaemia, and analyses were conducted in which a utility associated with the flexible dosing of degludec was captured.In an additional sensitivity analysis, long‐term costs and clinical outcomes with degludec vs glargine U100 were simulated over a 50‐year time horizon in the IQVIA CORE Diabetes Model version 9.0  using cardiovascular risk equations from the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model 2 and parameters detailed in Table A probabilistic sensitivity analysis (PSA) was conducted to quantify the effect of statistical uncertainty around all relevant input parameters concerning cost and effectiveness outcomes Table . Uncerta33.1Our evaluation of discounted direct costs suggested that there would be a mean cost saving of CAD 128.58 per patient with degludec as compared to glargine U100 over a 2‐year time horizon Table . The mos3.2Favourable cost‐utility results with degludec as compared to glargine U100 were insensitive to changes in most parameters Table . DegludeThe vast majority of points on the incremental cost‐utility scatterplot were on the right‐hand side, indicating improved effectiveness with degludec as compared to glargine U100, with most points specifically in the lower right quadrant, demonstrating that costs were also lower with degludec over the 2‐year time horizon  uniform requirements for authorship and that they have contributed to critical analysis and interpretation of the data, to drafting and/or critically revising the article, and they share final responsibility for the content of the manuscript, as well as the decision to submit for publication.The datasets generated and/or analysed during the current study are available from the corresponding author upon reasonable request.FIGURE S1 Schematic illustration of the cost‐utility modelFigure S2 Long‐term modelling extension scenariosTable S1 Cox regression model of time to first event of severe hypoglycaemia in DEVOTE (N = 7637)Table S2 Baseline characteristics for the DEVOTE subgroup at high risk of hypoglycaemiaTable S3 Overview of cost and QALY calculations for complicationsTable S4 Long‐term extension modelling parameters (at baseline)Table S5 Overview of the long‐term extension sensitivity analysis methodology and simulated resultsTable S6 Parameter inputs for the probabilistic sensitivity analysisClick here for additional data file.


Recent advancements in bioanalytical techniques have led to the development of novel and robust diagnostic approaches that hold promise for providing optimal patient treatment, guiding prevention programs and widening the scope of personalized medicine. However, these advanced diagnostic techniques are still complex, expensive and limited to centralized healthcare facilities or research laboratories. This significantly hinders the use of evidence‐based diagnostics for resource‐limited settings and the primary care, thus creating a gap between healthcare providers and patients, leaving these populations without access to precision and quality medicine. Smartphone‐based imaging and sensing platforms are emerging as promising alternatives for bridging this gap and decentralizing diagnostic tests offering practical features such as portability, cost‐effectiveness and connectivity. Moreover, towards simplifying and automating bioanalytical techniques, biosensors and lab‐on‐a‐chip technologies have become essential to interface and integrate these assays, bringing together the high precision and sensitivity of diagnostic techniques with the connectivity and computational power of smartphones. Here, we provide an overview of the emerging field of clinical smartphone diagnostics and its contributing technologies, as well as their wide range of areas of application, which span from haematology to digital pathology and rapid infectious disease diagnostics. With the escalating use of smartphone devices in everyday life, there has been a rapid growing trend for adapting them into sensing and diagnostic needs related to medical health care In principle for m‐Health applications, pictures of physical signs can be captured, shared and used remotely for an initial assessment by a physician. By this, the diagnosis can be delivered quickly, and the proper encryption data can not only be efficiently recorded but also instantly shared with healthcare professionals in different locations. Mere physical signs, on most of the cases, are however, insufficient to provide an accurate diagnosis or drive a medical decision. Therefore, additional routine tests are performed at a centralized clinical laboratory to provide a specific analysis that can lead to evidence‐based decisions. This is critical for a successful treatment, management and the delivery of an integral and quality health care Smartphones, albeit not being designed and developed for clinical applications, can be adapted for this purpose using compatible attachments that include the necessary hardware to perform microscopic imaging, and interface with diagnostic tests integrated in lab‐on‐a‐chip devices Fig.  8, 9, 10The aim of this review was to provide a comprehensive overview of the parallel technology advancements that have contributed to the emergence of smartphone‐based diagnostics. These include advances in bioanalytical methods, as well as technologies such as CMOS imagers, light‐emitting diodes (LEDs) and 3D‐printing techniques that are used to engineer the interfacing smartphone attachments Fig. . A note Developments in the fields of analytical chemistry, molecular biology and biosensors have enabled the detection of biomarkers with an unprecedented resolution, precision and clinical relevant sensitivities. A number of techniques and methods have become available and have evolved into well‐stablished and routinely practised tests and platforms used for clinical analysis of samples such as saliva, blood, urine, stools and tissue sections. From the plethora of clinical tests available at centralized laboratories, there are a number of methods that hold a great value in improving the efficiency of health care delivery if they could be performed at POC settings Since its introduction by Kircher in the 17th century 2O2, and second horseradish peroxidase (HRP) in the presence of the generated H2O2 acts upon a chromogenic substrate producing an apparent colour change  tests such as enzyme‐linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR), and in situ analysis techniques such as immunohistochemistry (IHC) and in situ hybridization (ISH).With the continuous advancements in the field of molecular biology, the detection of biomolecules such as DNA, RNA and proteins with sequence and single‐molecule resolution in complex clinical samples has become practically relevant and possible. Although most of the modern molecular techniques are restricted to research purposes mainly due to their high cost, specialized training and required infrastructure, a number of tests are becoming gold standards in routine clinical analysis. These include Enzyme‐linked immunosorbent assay is an extensively used IVD immunoassay to determine serum protein concentrations and the presence of viral or bacterial antigens Regarding nucleic acid IVD tests, PCR is the most commonly adapted technique and it is currently becoming a gold standard for viral diseases including rhinovirus, influenza and HIV Nucleic acid testing also offers the possibility for highly multiplexed assays that allow parallel detection and discovery of sequences, which is valuable for complex genetic diseases such as cancer. Therefore, the use of additional read‐out technologies such as microarrays and sequencing permits for higher throughput and to obtain information with higher precision and detail. Popular methods including microarray‐based IVD tests are being implemented for diagnosing diseases such as breast cancer, monitoring therapeutic response and generally genetic screening for congenital anomalies in situ methods that allow to perform immunoassays or nucleic acid detection directly on histological preparations have also become relevant for clinical practice, such is the case of IHC and ISH techniques in situ hybridization (FISH) is used for the analysis of cytogenetic abnormalities such as aberration copy number variations, duplications and translocations that are used to diagnose a number of diseases including chronic myeloid leukaemia and breast carcinomas Furthermore, Besides these routinely used methods, there are a number of emerging molecular technologies that despite being limited to research laboratories, and in an early stage of commercialization, hold a great promise in transforming the clinical diagnostic field. Of particular interest are a number of microscopy‐based methods used for spatially resolved genomics, transcriptomics and proteomics because they allow for the quantification and analysis of biomarkers at the single cell level with an unprecedented precision and detail. The clinical validation of these methods as well as developments that allow to bring them to a clinical use is of high relevance for the development of personalized precision medicine.in situ sequencing (ISS), aiming to provide parallel detection of nucleic acid targets with spatial, sequence and single‐molecule resolution in preserved cells and tissues in situ and in vitro diagnostics In the forefront of microscopy‐based spatial analysis methods lies The development and implementation of the above‐mentioned analytical techniques have heavily relied on its integration with technologies that allowed to extend their use for clinical purposes. Towards POC diagnostics, biosensing and microfluidic platforms have permitted the development of rapid and affordable concepts based on methods that were confined to research laboratories. In this section, we provide an overview of the principles and importance of these fields for the development of portable diagnostics systems.Biosensors are analytical devices designed to detect biomarkers by transducing a biological response/interaction into a detectable output signal, for instance optical, electrical or magnetic. Biosensors are comprised of three main parts: (i) the biological recognition element for target identification, (ii) a physical transducer that converts the biorecognition event into a measurable signal and (iii) a converter that translates the signal into a readable form Additional biosensing approaches for enhanced optical detection include quantum dots (QDs) Microfluidic systems have become essential for the development of POC diagnostics because they allow consistent miniaturization, integration of complex bioanalytical assay protocols and have been of central importance for the development of biosensors. Going down to the microscale poses several superior properties including small volume requirements, small thermic mass and high surface‐to‐volume ratio, which account for decreased reagent use, shorter incubation times, parallel processing and portability Microfluidic devices can be manufactured using a variety of materials including glass, silicon, thermoplastic polymers and paper Recently, 3D printing has become an emerging technology that holds promise of being production scalable, cost‐effective as well as rapid, versatile for manufacturing custom‐made designs and offering high precision, thus rendering it as a beneficial technology for the production and low‐cost prototyping of POC devices From the read‐out point of view, except for those tests that can be read by naked eye, most of the described platforms and technologies rely on optical or electrical detectors that require either specialized instrumentation, expensive hardware components or computational power to acquire, analyse and deliver data. Smartphones have evolved into powerful portable gadgets that integrate high processing power, together with physical sensors and connectivity. The image sensors within the smartphone's camera module are sensitive enough for many diagnostically relevant applications. Details outlined below highlight the recent progress in developing various optomechanical attachments to turn smartphones into robust read‐out devices for diagnostics without permanently altering the phone. Most of these devices have also been designed to limit manufacturing costs which is essential in lowering the barrier between low resource settings and modern medical techniques.Smartphone cameras use low‐cost CMOS technology, which are able to detect red, green and blue (RGB) light and therefore ideal for optical quantification in the visible wavelength range. An initial application of the integrated CMOS sensors in smartphones was to use them as external cameras for capturing images from the microscope ocular using 3D‐printed adapters 2 can be achieved. By further trading off some of the resolution, the authors were able to increase the effective FOV to 15.7 mm2 whilst still keeping the spatial resolution below 10 μm.A query of the correlation of resolution to pixel density in smartphone image sensors was performed by affixing an objective lens and eyepiece to a smartphone Perhaps the least complicated and most cost‐effective method for converting a smartphone into a brightfield microscope is the inkjet printing of lenses using (polydimethylsiloxane) PDMS Finally, some recent results have also demonstrated the use of machine‐learning techniques, in particular deep neural networks, to enhance mobile microscopy images by correcting the spatial and spectral aberrations in the raw acquired images of mobile phone‐based microscopes Fluorescent microscopy is essential for modern biomedical diagnostics. To this application, smartphones have proven themselves to be more than capable of delivering diagnostically relevant results when equipped with the proper attachments. A typical smartphone fluorescence microscope consists of an excitation light source (LED or laser diode) and an emission filter, in addition to the above‐mentioned external lenses with the brightfield modality. How the samples are illuminated is the key consideration when designing a smartphone‐based fluorescence microscope. For samples such as cuvettes or tubes, an orthogonal illumination to the detection path provides a simple means of high signal‐to‐noise ratio (SNR) fluorescence detection Due to the small pixel sizes and larger operating temperature, smartphone devices are in general not as sensitive to light signals as their commercial counterparts. However, to enhance the fluorescence detection the use of glass capillary tubes as sample containers are useful for both reducing sample volumes and improving detection sensitivity Some approaches are currently investigated to mitigate the limiting SNR that is typical of smartphone image sensors error, for instance, a radiometric method where two different wavelengths corresponding to the analyte were measured simultaneously instead of the typical one. By observing the correlation of the two wavelengths false‐positive and false‐negative signals could be discarded with more accuracy Smartphone‐based spectroscopy has seen much more attention as image sensor quality continues to improve. The high precision requirements of spectroscopic methods have been prohibitive in the past but as smartphones continue to get more sophisticated so do the applications for which they qualify. The optical design to achieve spectrophotometric measurements is relatively simple Fig. c. An incBackground illumination is always a challenge when designing spectroscopic systems. This problem exacerbates when the system must be portable and easily attached to a smartphone. This was addressed in a study using a fibre‐optic bundle to direct light from the smartphones flash directly onto the sample Phase imaging is a desirable capability of portable imaging devices because it allows the analysis of transparent samples without staining or dyeing Smartphone‐based differential phase contrast (DPC) microscopy can also be achieved in a single‐shot image by asymmetric illumination patterns using LED arrays. Images are reconstructed from two sequential images acquired with complementary illumination patterns which in this case are using half of the LEDs Light scattering is an essential method for noninvasive analysis of suspended particles in solution. As such, the adaptation of smartphones into light scatter sensors can be utilized to perform on‐site medical diagnosis. The viability of the smartphone platform for scattering‐based sensing was examined using simple optical elements and a laser to determine the mean size of suspended particles within a 20 nm accuracy The adaption of smartphones as imaging read‐out platforms in the clinic could be used for on‐site data acquisition, analysis in a real‐time mode, management of the generated information at the convenience of the user and enormously fast transfer of data from the site of detection to healthcare professionals. Before the last decade, clinical analytical methods and smartphone technologies were independent disciplines; in this section, we include a review of the smartphone‐based imaging systems that combine these disciplines with diagnostic purposes. Table et al. Bacillus anthracis spores on a microfluidic incubation chip. This system was capable of detecting from 50 to 5000 spores in a period of 3–5 h. Furthermore, field tests in rural Ghana and Côte d'Ivoire were conducted to evaluate the performance of a smartphone‐based brightfield microscope Schistosoma mansoni and S. haematobium eggs in stool and stained urine samples Loa loa filariasis on whole blood thick smears of 300 samples achieving a specificity and sensitivity of 94% and 100%, respectively In a study by Hutchison Moreover, malaria parasites, sickled blood cells and tuberculosis (TB) bacilli have been captured with a high resolution with smartphone microscopes that include brightfield and fluorescence in blood and sputum samples + ions in sweat and saliva samples  DNA without a thermocycler was adapted to a smartphone read‐out. The study reports a clinical evaluation study with 60 samples resulting in assay accuracies of up to 100% Smartphones are equipped with advanced physical sensors including gyroscopes and magnetoscopes. Multiple concepts are being developed to equip smartphones with biosensing capabilities exploiting the advantages of combining established biosensing platforms with the inherent properties of smartphones including analytics, portability and connectivity. To this end, optical paper‐based biosensors are in particular advantageous because the interfaces can be quite simple. Barcode‐like paper sensors with developed apps for image acquisition and analysis have been demonstrated for applications such as blood typing haematocrit level determination, glucose and uric acid measurements Other optical smartphone biosensing platforms based on the SPR properties of gold nanoparticles (AuNPs) have been proposed as diagnostic tools E. coli O157:H7 down to 10 CFU μL−1 with a smartphone using QDs and capillary arrays et al. 3 to 109 copies mL−1. The sensitivity of the fluorescence resonance energy transfer (FRET) between QDs donors and Cy3 acceptors was also exploited as a means to perform radiometric sensing of nucleic acid hybridization events on a μPAD platform Additional approaches have reported the detection of 2 microglobulin with a LOD of 0.1 μg mL−1 using a commercial SPR sensor chip Label‐free smartphone biosensors approaches mainly based on SPR measurement detection for protein detection are also available. Actual smartphones screens provide more than sufficient wide‐angle illumination to perform SPR measurements. For example, using a screen side optical attachment, it was possible to detect human βet al. developed a portable and equipment‐free biosensor for colorimetric detection of the Plasmodium falciparum lactate dehydrogenase enzyme for malaria diagnostics. They reported 90% sensitivity and specificity for clinical samples using their three‐chamber microfluidic chip in combination with automated smartphone read‐out Finally, electrochemical biosensors have also been used in combination with smartphones. Examples include a potentiostat for monitoring lung infections in cystic fibrosis patients by tracking the concentration of secretory leucocyte protease inhibitor. This was achieved using an electrochemical ELISA platform that is plugged into the audio port of the smartphone Fig. f 160. FrSmartphone‐based diagnostics is a powerful approach that could strongly influence how medicine is currently being practised, probably and hopefully in a similar manner as how smartphones revolutionized communications. The implementation of these systems into the medical practice could not only allow the decentralization of medical specialties such as oncology, haematology and virology, but also allow for fast disease data acquisition, storage and management. This could have a significant impact for epidemiology and public health because attached to the diagnostic test result, accurate geographic and demographic data can be stored. Furthermore, exploring and understanding the limitations regarding the viability of these platforms for field use are going to be essential for moving forward towards bedside diagnostics and democratization. For a system to be truly universal, it must be able to be affordable for those with very limited means; therefore, an important direction of research in any of these methods will be further reduction in the costs. This is especially the case for advanced molecular methods that require expensive reagents and special storage/transport conditions. Commercialization approaches that invest on increasing the scalability and robustness of the assay/test are essential to achieve cost‐effective and robust platforms designed for limiting and harsh conditions. Furthermore, assay integration plays a central role in this regard to be able to deliver platforms that can be interfaced with both the optical and electrical components of smartphones.www.fairphone.com) or the shelved project ARA will be crucial to enable scalable manufacturing of smartphone technology‐based diagnostic devices. For instance, CMOS sensors can be used to build lens‐free microscopy systems that hold promise for on‐site diagnostics because they allow for wide FOVs, which could be relevant for infectious diseases such as malaria and TB An important consideration is the availability of off‐the‐shelf smartphone components that would allow their use in a modular fashion. Initiatives like fair phone (The studies mentioned in this review demonstrate that sensitive and specific bioanalytical assays are already available in a number of formats and at different levels of integration with smartphones. However, most of the reported approaches are in a proof‐of‐concept phase or constitute isolated efforts, and just a few are in commercialization or productization stage. Further focus is to be laid on validating these platforms and assessing their feasibility in clinical settings. In the near future, it is certain that smartphone‐based diagnostics would strike the needed balance between molecular methods and compatible technologies for bedside diagnostics, thus becoming a central part of the m‐Health ecosystem, and ultimately democratizing evidence‐based medicine.A.O. reports grants from NSF during the conduct of the study and other from Holomic LLC, outside the submitted work; in addition, A.O. has several pending patents on mobile diagnostics and imaging systems with royalties paid. The remaining authors have nothing to disclose.


Increasing vapor pressure deficit (VPD) increases atmospheric demand for water. While increased evapotranspiration (ET) in response to increased atmospheric demand seems intuitive, plants are capable of reducing ET in response to increased VPD by closing their stomata. We examine which effect dominates the response to increasing VPD: atmospheric demand and increases in ET or plant response (stomata closure) and decreases in ET. We use Penman‐Monteith, combined with semiempirical optimal stomatal regulation theory and underlying water use efficiency, to develop a theoretical framework for assessing ET response to VPD. The theory suggests that depending on the environment and plant characteristics, ET response to increasing VPD can vary from strongly decreasing to increasing, highlighting the diversity of plant water regulation strategies. The ET response varies due to (1) climate, with tropical and temperate climates more likely to exhibit a positive ET response to increasing VPD than boreal and arctic climates; (2) photosynthesis strategy, with C3 plants more likely to exhibit a positive ET response than C4 plants; and (3) plant type, with crops more likely to exhibit a positive ET response, and shrubs and gymniosperm trees more likely to exhibit a negative ET response. These results, derived from previous literature connecting plant parameters to plant and climate characteristics, highlight the utility of our simplified framework for understanding complex land‐atmosphere systems in terms of idealized scenarios in which ET responds to VPD only. This response is otherwise challenging to assess in an environment where many processes coevolve together. We derive a simplified analytical model for ecosystem‐scale evapotranspiration response to changes in vapor pressure deficitEcosystems exhibit a range of behavior, from reductions to increases in evapotransipration, in response to increasing vapor pressure deficitThe choice of stomatal conductance model fundamentally alters the relationship between evapotranspiration and vapor pressure deficit At this stage, any further increase in VPD will most likely drive a (limited) increase in ET, because the increase in atmospheric demand for water overwhelms the limited plant response to conserve water.The objective of the present manuscript is to use reasonable approximations established in prior research as a tool to develop a framework for understanding plant responses to atmospheric drying and the VPD dependence of ET while keeping other variables fixed. This framework will aid interpretation of observations and full complexity models and facilitate the disentanglement of complex land‐atmosphere feedbacks. In particular, our approach has applications for understanding climate change impacts, given expected increases in VPD with rising temperature. In the past, similar simplified approaches were used to understand interactions between stomatal conductance, ET, and the environment , including VPD response, by combining an optimal photosynthesis theory , ET, and VPD over a diurnal cycle at the ecosystem scale. uWUE is also relatively well conserved in the growing season across space and time, within a plant functional type  future research on stomatal conductance and ecosystem‐scale modeling and (2) thoughtful selection of photosynthesis and stomatal conductance models in more sophisticated land surface and Earth system models.2desdT), Rnet is the net radiation minus ground heat flux, ga is aerodynamic conductance, ρa is air density, cp is specific heat of air at constant pressure, γ is the psychometric constant, and gs is the stomatal conductance .The PM equation  by combining an optimal photosynthesis theory  to physical parameters as 1 is presented in units of mol fraction for convenience , Γ* is the CO2 compensation point for photosynthesis (without dark respiration), and λ is the marginal water cost of leaf carbon  uWUE leverages the same assumptions used in Medlyn et al. , and uWUE. For the first time, we have removed the implicit dependence of ET on itself through the stomatal conductance term, and we have also replaced the added complexity of a stomatal conductance reduction factor and a photosynthesis model with a single parameter (uWUE). Both the plant parameters reflect water conservation strategy. The slope parameter is related to the willingness of stomata to trade water for CO2 and to keep stomata open (carbon cost in terms of water). uWUE is a semiempirical ecosystem‐scale constant related to how WUE changes with VPD . It is also roughly proportional to physical constants: 2 compensation point (equation (5) in Zhou et al., uWUE is related to atmospheric CO2 concentration and compensation point and is inversely proportional to the marginal water cost of leaf carbon (λ). This relationship with λ (∝λ−1/2) is important as it is the inverse of g1's relationship with λ (∝λ). So uWUE should increase as λ decreases, and g1 should decrease as λ decreases.By accounting for photosynthesis changes in ecosystem conductance, with equation desdT) and VPD are functionally related, so while taking the derivative, we evaluate ∂ET∂VPD=∂ET∂es∂es∂VPDRH fixed+∂ET∂RH∂RH∂VPDesfixed. RH and es are assumed to be approximately independent, which is supported by data , when relatively high insolation induces instability and convective boundary layers, and we would expect the surface to be generally well coupled. An additional assumption in the formulation of uWUE  is particularly interesting because soil moisture only enters the partial derivative directly through these plant parameters. If the plant parameters are weak functions of soil moisture, then the theory can be directly applied to a broader range of conceptual VPD scenarios, including observed compound events between high VPD and low soil moisture  are fixed with respect to the user's conceptual change in VPD. Care must also be taken with possible indirect effects associated with a change in VPD: For example, a change in ET induced by a change in VPD can cause a change in surface temperature, which would drive a change in net radiation. These types of indirect effects and feedbacks are not considered in equation Because equation 2.1To account for both the variability in plant parameters and the environment, we will systematically analyze how the ET response to VPD equation  varies. g1 and uWUE. In the scaling term, most of the terms are relatively constant with the exception of aerodynamic conductance (ga) and temperature . To determine the range of probable ET responses to VPD, we will systematically vary these parameters according to Table ga and T) and plant physiological parameters (g1 and uWUE) are varied according to literature‐based expectations for a range of growing season conditions and plant types .All code and data used in this analysis, including those used to generate the figures and tables, are publicly available online  at three different values (Table ∂ET∂VPD). To aid visualization, we can examine a subset of nine of these 81 curves, defined by the minimum, median, and maximum values for both the scaling and sign term  or water intensive , and smaller g1 values lead to a larger VPD dependence of the response . However, care should be exercised when interpreting the range of ET responses, because g1 and uWUE should generally be anticorrelated due to their dependencies on λ. As λ increases, g1 should increase, and uWUE should decrease. Because high and low values of uWUE and g1 were determined independently from each other in previous literature, plant types with anomalously high or low values for bothg1 and uWUE should be relatively rare. However, some plant types do exhibit cooccurring high values for g1 and uWUE. For example, C3 crops have both the highest g1 value in Franks et al.  and temperature (controls the efficiency of energy conversion to latent heat through Δ) amplify or suppress the plant response represented in the sign term Figure . Both lo4g1 and uWUE. Equation g1 and uWUE may vary with plant species and environmental conditions like soil moisture, we can still assess the ET response to VPD for a given ecosystem state or for a given soil moisture condition.Interpreting both the derivation and results of this manuscript hinges on an understanding and appreciation for the usefulness of partial derivatives for understanding the behavior of complex systems in a simplified framework. Our results are a conceptual tool for answering the question, “What is the ET response to VPD with all other quantities held fixed?” This is useful, and we would argue that this is critical, for understanding complex responses when many quantities are varying simultaneously  that was demonstrated by Zhou et al. . These differences between leaf‐scale behavior and ecosystem‐scale behavior highlight the importance of understanding how and why slope parameters show increased variability at the ecosystem scale, as argued by Medlyn et al.  and a smaller VPD dependence of the ET response.For all of the above relationships, a higher Our theoretical results highlight the variability of ET response to VPD as a function of both climate and plant characteristics, especially water usage strategy. Whether an ecosystem increases or decreases ET in response to VPD will vary depending on vegetation and climate. Generalizations about ET response to VPD therefore require thoughtful consideration of ecosystem characteristics; statements such as “ET increases with warming due to increases in VPD” may be false depending on the water conservation strategy of a given ecosystem  within a given plant functional type, and research derived from these models often does not acknowledge limitations of this assumption or the difficulty in the literature with quantifying an ecosystem‐scale slope parameter  to remove the implicit dependence of stomatal conductance on ET, is flexible enough to be applied to any stomatal conductance model that contains a dependence on GPP.Additionally, the sensitivity of ET response to plant parameters highlights the importance of understanding and developing stomatal conductance models and parameters for the ecosystem scale. In particular, why and how uWUE based on the assumption that stomata behave to maximize carbon gain while minimizing water loss, which observations also generally support  are held fixed. This result warrants further investigation, because to our knowledge, no earlier work has derived the theoretical ecosystem‐scale relationship between ET and VPD in an energy balance framework while controlling for other environmental conditions. In particular, there is an apparent lack of consensus over whether the shape of the ET‐VPD curve should be concave upward (our result) or concave downward in the absence of dramatic water stress. Given that understanding the ET‐VPD relationship of the one‐way plant response is fundamental to hypothesizing about any feedbacks between the land surface and the atmosphere, we analyze why our derived ET‐VPD relationship is concave upward, particularly with respect to the exponent of VPD dependence in uWUE and the Medlyn unified stomatal conductance model, as other models and empirical results have suggested exponents varying from 1/2 , with respect to VPD: By introducing VPDm/g*). Several important relations reveal themselves from equation n, m = 1/2), the ET‐VPD curve will be concave up regardless of the magnitude of the plant constants g1 and uWUE. Therefore, the general concave up nature of our results, given an assumption of optimal behavior, is insensitive to plant type.For optimal behavior , whether the solution is concave up or concave down does not depend on *WUE.For all physically possible exponents of VPD dependence . Because the exponent of the VPD dependencies is capable of altering the fundamental shape of ET‐VPD dependence, future research investment in understanding the exact VPD dependence of stomatal conductance and further reconciliation of empirical and theoretical stomatal and ecosystem behavior should be prioritized.In general, increasing the exponent of VPD dependence for either *With this result, we have defined the family of curves separating concave up from concave down ET solutions Figure . These cn=m=1/2 as the most likely candidate given current theory and empirical data. Additionally, we argue that a concave up result matches physical intuition more than a concave down result. Plants must maintain nutrient and sugar transport through the phloem and xylem. To accomplish this, stomata must remain slightly open  that in the future, some other form of VPD dependence is derived, at present  environmental conditions over the relatively coarse  flux estimates (which is required to obtain robust eddy covariance statistics). Our results on the shape of the ET‐VPD curve with environmental conditions held fixed can be built upon with future work examining how changes in VPD and environmental conditions  feedback upon one another. In the soil water storage example, over very long time scales, extremely high VPD perturbations coupled with no precipitation could result in decreases in soil water storage such that water becomes limiting. This could be represented by an extension of our framework in which 5uWUE , C4 plants (lower g1), gymnosperm trees (lower g1), and plants in arctic and boreal climates (lower g1) are more likely to exhibit a negative ET response to VPD. However, interpretation of g1‐induced variability is partially muddied by ambiguity in applying leaf‐scale estimations of g1 to the ecosystem scale  to strongly water intensive (ET increasing in response to VPD), which is indicative of the diversity of possible plant water conservation strategies. Higher ∂ET∂VPD=0. However, future research should focus on fully understanding the functional form of VPD dependence, as this concave up result is sensitive to the exponent of VPD dependence, which we currently believe is 1/2 for both uWUE and the stomatal conductance model (Medlyn et al., Our paper builds intuition for how plants respond to VPD perturbations. We show that given optimal stomatal function and fixed environmental conditions, the ET‐VPD dependence is theoretically concave upward, with ET increasing with increasing VPD as VPD increases past some critical value where 2 effects (e.g., Lemordant et al., g1 (e.g., Lin et al., uWUE (e.g., Zhou et al., 2 world.Our results are also applicable to understanding the impact of expected increases in VPD induced by global change. Plant physiological responses to direct COSupporting Information S1Click here for additional data file.