The current clinical practice of assessing the quality and suitability of a donor liver for human transplantation does not exclude cases of primary graft dysfunction of the transplanted organ and, at the same time, leads to an unreasonable refusal to transplant a significant number of functionally suitable organs. In this regard, searching for new methods for additional objective assessment and monitoring of the state of donor organs in the peritransplant period is relevant.The aim of the study was to determine the clinical utility of monitoring interstitial concentrations of glucose and its metabolites to assess the viability and functional state of a donor liver before and after human transplantation.A retrospective observational single-center study included 32 cases of liver transplantation. Along with standard methods for assessing the initial function of grafts during the first week after surgery, interstitial (in the transplanted liver) concentrations of glucose and its metabolites were monitored. In 18 cases, the interstitial glucose metabolism was also studied during static cold storage (SCS).With the development of early allograft dysfunction (EAD), compared with the uneventful post-transplant period, statistically significantly higher interstitial lactate concentrations were observed as early as 3 h after reperfusion: 12.3  mmol/L versus 7.2  mmol/L (p=0.003). A value above 8.8 mmol/L may be considered as a criterion for the immediate diagnosis of EAD .Interstitial lactate concentration at the end of SCS and the area under the “lactate concentration–SCS duration” curve were associated with the initial graft function. Values of these parameters greater than 15.4 mmol/L and 76.1 mmol/L·h, respectively, with a sensitivity of 100% in both cases and a specificity of 77 and 85%, may be used to assess the risk of primary EAD.Monitoring of interstitial concentrations of glucose and its metabolites, primarily, lactate, is an objective additional method for the assessment of the donor liver viability both during SCS and in the early postoperative period. Over the past two decades, the number of liver transplants performed annually in Russia has increased almost fiftyfold: from 12 operations in 2000 to 584 in 2019  and EuroObviously, the extension of the criteria for a deceased donor liver suitability for transplantation, on the one hand, increases the number of procedures performed and reduces mortality among transplant candidates, and, on the other hand, it increases the risk of primary non-function or early allograft dysfunction (EAD) after transplantation, which affects the immediate and long-term outcomes of the operations and increases the need for repeated transplantations.Current clinical practice involves the assessment of the quality of a donor organ and the feasibility of its subsequent transplantation based on the results of a number of standard laboratory and instrumental tests of a potential donor (a person with an established diagnosis of brain death) before the procurement, as well as during the surgery based on the subjective visual assessment. In some cases, an urgent histological study is acceptable, which, however, is not common due to the possible increase in the time of graft preservation and only an indirect assessment of the functional suitability of the organ. The existing approaches allow for the risks of primary non-function (PNF) graft and at the same time lead to unreasonable refusal to transplant a significant number of organs, which have been found unsuitable because of an erroneous subjective assessmentTaking into consideration the limited diagnostic and prognostic potential of routine methods, we decided to initiate a scientific clinical study aimed at searching and determining the effectiveness of additional objective methods for assessing the viability and functional state of the donor liver during preservation and in the early post-transplant period. Based on the analysis of the literature and the available technological potential of the clinic, interstitial microdialysis with the assessment of glucose metabolism parameters has been chosen as the study method.The work was carried out in the Laboratory of New Surgical Technologies and subdivisions of the Surgery and Transplantation Center of the Burnazyan Federal Medical Biophysical Center of FMBA of Russia. It was a two-stage observational study ; its resAt stage I , interstitial metabolism was studied only in the early postoperative period: from the completion of transplantation to the end of the 7th postoperative day. This part of the work included 14 observations, in 5 cases of which the right lobe of the liver from a living donor was transplanted.At stage II , the period of sample collection and analysis of the composition of interstitial fluid was extended and lasted since the beginning of graft explantation, during the period of static cold storage (SCS) and transportation of the donor organ, as well as during the first week after surgery. There were 18 observations at stage II, all the organs were obtained from deceased donors.In this way, 32 recipients were monitored for the parameters of interstitial metabolism after transplantation . The analyses of the observations were put together in order to study the dynamics of the interstitial concentrations of glucose, lactate, pyruvate, and glycerol in the early postoperative period, to establish their relationship with the initial function of the grafts (assessed on the 7th day), as well as with the immediate outcomes of operations (assessed on the 7th and 30th days).To study the impact of the parameters of interstitial metabolism during SCS on the severity of ischemic and reperfusion injury (IRI) and the initial function of the transplanted liver, 18 cases were analyzed separately, in which the study was also carried out during SCS and donor organ transportation.Early allograft dysfunction was defined according to criteria by Olthoff et al. : the levTo deal with each of the issues see , all theOut of 18 cases included in the second part of the analysis, 13 patients had an uneventful postoperative course (group C), EAD was diagnosed in 5 recipients (group D), and no cases of PNF were noted.32 patients (21 men and 11 women) aged 38 to 68 years (the median was 53 years) were transplanted. All the procedures were primary. The indications for surgery were liver cirrhosis (LC) caused by viral hepatitis , hepatocellular carcinoma associated with LC of viral etiology (n=8), cholestatic liver diseases (n=3), unresectable liver alveococcosis (n=3), LC as a result of non-alcoholic steatohepatitis (n=2), alcoholic LC (n=2), LC of unknown etiology (n=2). Severity assessment by the MELD score varied from 7 to 40 points (the median was 15).In 5 cases, the graft of the right lobe of the liver was obtained from living-related donors (3 men and 2 women) aged 22 to 49 years (the median was 32 years). Graft weight varied from 732 to 1130 g (median 885 g), the graft-recipient weight ratio ranged from 1.15 to 1.41% (the median was 1.25%).In 27 cases, an organ for transplantation was obtained from deceased donors (18 men and 9 women) with established brain death, resulted from cerebrovascular accident (n=21) and severe traumatic brain injury (n=6). Donor age ranged from 20 to 67 years (the median was 48 years). The mean time spent on mechanical ventilation before retrieval was 3 days (from 1 to 6). In all the cases, hemodynamics was stable, without hypotensive and/or asystolic episodes. The results of the laboratory tests immediately before procurement were as follows: sodium — 147 (129–163) mmol/L, AST — 48 (14–200) U/L, ALT — 38 (7–110) U/L, total bilirubin — 10.2 (2.0–16.6) μmol/L. The median cold ischemia time (CIT) of the organs obtained from deceased donors was 9.0 (from 3.6 to 13.5) h. In 21 cases, aircraft transport was used for transportation. The CIT in living-donor liver transplants ranged from 30 min to 1 h 20 min (the median was 45 min).The principle of microdialysis and its application in liver transplantation are known and described earlier -8, as weWhen an organ was procured from a deceased donor, a microdialysis catheter was placed in segment IV of the liver to obtain interstitial fluid samples immediately after sternolaparotomy and the initial stage of liver mobilization  on the preserved blood flow. The catheter was fixed with a ligature to the falciform ligament, filled with perfusion fluid, and connected to a microdialysis pump. The pump was placed inside a sterile surgical glove, which was hermetically tied with a ligature and attached to the surgical drapes. 20 min after perfusion started, a sterile microtube was placed in the catheter port to collect interstitial fluid. Changing microtubes  was performed once an hour until the organ was delivered to the operating room of the transplantation center. The feed rate of perfusate into the catheter was 0.3 μl/min.After explantation, the organ was packed in the standard manner in three sterile plastic bags, with a microdialysis catheter sequentially passed through the node of each of them. When packing was completed, the sections of the catheter with a port for microtubes and connecting a microdialysis pump became non-sterile. The packed organ was placed in a transport isothermal container. Before unpacking the donor organ, the outer non-sterile part of the catheter was cut off; then unpacking was performed in the traditional way. Before starting the graft processing, the microdialysis catheter placed at the time of excision was removed.A catheter for collecting samples of interstitial fluid in the early postoperative period was placed in the graft parenchyma immediately before suturing the surgical wound, brought out through the counteropening to the anterior abdominal wall and fixed to the skin.In case of transplantation from a living donor at the stage of donor right-sided hemihepatectomy, after liver mobilization, before parenchyma splitting, a microdialysis catheter under ultrasound control was placed at the border of segments VII and VIII and fixed with a ligature to a fragment of the right triangular ligament.After transplantation, the microtubes were changed every 3 h until the 7th postoperative day. During the study, the microdialysis pump was placed and fixed on the anterior abdominal wall of the patient. After sampling was completed, the microdialysis pump was turned off, and the catheter ports were closed. The catheter was removed on the 10–14th postoperative day, then a control abdomen ultrasound was performed.Microdialysis catheters for hepatic tissue , Perfusion Fluid T1, 106 Microdialysis Pump, syringes for microdialysis pump (106 Syringe), and special microtubes with a volume of 200 μl were used to obtain interstitial fluid samples. The composition of interstitial fluid samples was determined 2 times a day on the ISCUS Clinical Microdialysis Analyzer using Reagent Set B. All the equipment and consumables were manufactured by CMA Microdialysis AB (Sweden) and have a registration certificate for a medical device No.FSZ 2007/00697 dated November 28, 2007, valid in the Russian Federation. The results of the study were digitized.Quantitative variables were presented as the median values, with additionally indicating either the minimum and maximum values, when it was them that represented clinical significance, or giving the interquartile range absolute frequencies indicated qualitative features. The significance of differences in quantitative and qualitative variables in two independent samples was determined using the nonparametric two-tailed Mann–Whitney test and two-tailed Fisher’s exact test, respectively. Differences were considered statistically significant at p<0.050. When calculating the odds ratio of a binary outcome, a 95% confidence interval (CI) was also indicated. To find the boundary values of quantitative parameters, ROC analysis was performed, sensitivity and specificity were calculated. Calculations were performed using the Statistica 12 software package .The main characteristics of the recipients, donors, and transplants were matched by comparing groups A and B . By the st, 5th, and 7th days after surgery due to PNF, hepatic artery thrombosis, and progressive multiple organ dysfunction syndrome (MODS), as well as severe EAD after the development of malignant hyperthermia in the intraoperative period. All the early graft losses occurred in group B. By the 30th postoperative day (i.e. over the next three weeks), three more grafts were lost: two in group B (on the 22nd and 26th days as a result of the death of the recipients because of progressive MODS due to sepsis) and one case in group A .Assessment of the renal function of the recipients by the end of the first postoperative week demonstrated a statistically significantly higher frequency of episodes of acute renal injury (“Injury” and higher severity according to the RIFLE classification ) and a nth day because of the patient’s death from progressive MODS due to sepsis.Due to the fact that the observations of groups C and D , PNF was 3% (1/32); by the end of the first month after transplantation, 81% of recipients (26/32) were alive. In 5 of 6 cases of the loss of a transplanted liver, it occurred against the background of EAD/PNF. The odds ratio of graft loss in the development of early dysfunction, including PNF, was 27.5 (95% CI: 2.5–302.2).The dynamics of interstitial concentrations of glucose, lactate, pyruvate, and glycerol is shown in nd–3rd postoperative day;moderately increased, compared with normal values for capillary blood, interstitial glucose concentration during the first day tending to decrease to 5–10 mmol/L during the 2the maximum levels of lactate registered during the first hours after the operation and its subsequent decrease;an increase in the concentration of pyruvate in the first hours after the operation, reaching peak values after 18–24 h and then decreasing to 100–200 μmol/L.Higher concentrations of lactate (compared to the smooth course of the postoperative period) in the first measurement 3 h after reperfusion — 12.3  mmol/L versus 7.2  mmol/L (p=0.003), and after 24 h — 6.1  mmol/L versus 2.4  mmol/L (p<0.001), with subsequent retention of statistically significant differences throughout the entire observation period, should be considered the most important feature of the dynamics of interstitial concentrations of the studied parameters in group B, i.e. with EAD development .The ROC analysis determined the threshold value of interstitial lactate concentration to be 8.8 mmol/L. The use of the threshold value for the diagnosis of EAD provides 89% sensitivity, 65% specificity (the area under the ROC curve is 0.85).th–5th postoperative day, chronologically coincided with the termination of parenteral nutrition. None of the patients in group A received parenteral nutrition during the first week after transplantation.Statistically significant differences in interstitial glycerol concentrations , which pIn all the cases, the conditioning of deceased donors, procurement, preservation and transportation of donor organs were carried out by one surgical team in compliance with a single technology, the same criteria for assessing the quality and suitability of a donor liver for transplantation were used. Despite these facts, interstitial concentrations of the studied substances throughout SCS were ranged widely: glucose varied from 3.3 to 38.5 mmol/L, lactate — from 0.3 to 19.9 mmol/L, pyruvate — from 1 to 239 μmol/L, glycerol — from 6 to 1606 μmol/L. The universal trends were an increase in the concentrations of glucose , lactatein situ cold perfusion and at the end of SCS, the areas under the “concentration–SCS duration” curves ;primary EAD, the causes of which are the specific characteristics of the donor , the donor organ , as well as preservation , rejection, infections, cardiovascular and respiratory complications, should be considered as a separate condition.The methods for assessing the quality of the deceased-donor liver used in real clinical practice are, to a certain degree, subjective, and this is what complicates the differential diagnosis of primary and secondary EAD. Normothermic perfusion with oxygenated erythrocyte-based media becomes a solution to this problem and, in the vast majority of cases, makes it appropriate to use grafts of subjectively non-ideal  quality, excluding the risk of severe primary EAD and PNF . It shouIt is these circumstances, as well as a unique feature of the Coordination Center for Organ Donation of the Burnazyan Federal Medical Biophysical Center  that have become decisive for initiating and conducting stage II of this study, i.e. studying the features of interstitial glucose metabolism in the deceased-donor liver during SCS, assessing of their relationship with the IRI severity and the initial graft function. In the analysis of previously published works, we have found only one similar clinical study performed by Silva et al. , consistDespite the described advantages of the method of interstitial microdialysis, the practicability of its routine use in clinical practice is debatable. The retrospective nature of the results of the study of the transported donor organ is supposed to be the main disadvantage since the analysis of the composition of microsamples of the interstitial fluid is performed on the stationary equipment at the transplantation center. This either excludes the use of the results at the time of making a decision on the suitability of the organ for transplantation and the start of the operation in the recipient, or requires additional time to conduct the study after the delivery of the organ to the clinic, which causes a delay in the start of the operation until the results are obtained and, as a result, the SCS duration is extended by up to 2–3 h. Moreover, studying interstitial metabolism requires specialized equipment  and disposable consumables. Compared to the technology of isolated normothermic perfusion, their cost is significantly lower (by a factor of 10 or more), however, it demands leveraging additional financial resources: the study only during the SCS period accounts for about 70 thousand rubles, monitoring extension in the early postoperative period requires about 100 thousand rubles .Obviously, addressing these challenges rests exclusively in the area of technical implementation of the method for obtaining and analyzing the composition of interstitial fluid samples. We consider it to be promising to shift from the photocolorimetric method of measuring metabolite concentrations in the microsamples of interstitial fluid to the use of flow-through electrochemical sensors and obtaining the results of the analysis in real time. The development of a specialized monitoring module coupled with such sensors will provide sending data during transportation, and, if necessary, continuous measurement of other parameters .In our opinion, the creation of a portable medical device for monitoring the state of interstitial metabolism both during preservation and in the postoperative period for early diagnosis of functional disorders and vascular complications would provide adequate clinical studies in order to establish accurate diagnostic and prognostic criteria and be a decisive factor for the subsequent rapid and large-scale introduction of the interstitial microdialysis technology into the clinical practice of organ donation and transplantation. The opportunity of using the same device at all stages and for any options for static and perfusion preservation of organs provides formulation and proposal of a new concept for assessing their quality, predicting the risk of severe primary EAD and PNF . At the It should be underlined that the assessment of the parameters of interstitial metabolism during the preservation period and obtaining additional objective data on the state of the donor organ can be carried out not only for the liver. This is confirmed by the findings in published works on monitoring the state of the kidney in the experiment , 17 and The extension of the criteria for the suitability of donor organs for human transplantation is an inevitable process that has accompanied the entire history of clinical transplantation. The most efficient use of organs from deceased donors implies not only an increase in the number of transplants performed but also the achievement of satisfactory immediate and long-term results. This principle determines the extremely high relevance and need for search work and clinical studies of new technologies for the preservation and assessment of the viability of donor organs. One of the already ongoing activities is the development of methods and devices for isolated normothermic perfusion. Although, static cold storage has been and remains a reliable approach for organ preservation, the main disadvantage of which is the inability to monitor the organs’ condition. The findings of foreign studies, as well as the results of our own practice, allow us to rightly claim that the study of the parameters of interstitial metabolism of glucose (mainly lactate) will solve this problem.Moreover, the use of interstitial microdialysis in the early post-transplant period gives an immediate (within a few hours after reperfusion) assessment of the initial graft function, allows to differentiate primary and secondary EAD, and, accordingly, have a chance to adjust the intensive care plan in a preventive mode. Continued monitoring during the first days after surgery can be considered as a method for early diagnosis of vascular complications.Technical improvement of the process of collecting and analyzing samples of interstitial fluid and the creation of a medical device will be crucial for the further development and widespread implementation of the technology into clinical practice.


The peripartum period, defined as the period from the beginning of the gestation until 1 year after the delivery, has long been shown to be potentially associated with increased levels of stress and anxiety with regard to one’s transition to the status of parent and the accompanying parental tasks. Yet, no research to date has investigated changes in intrapersonal factors during the peripartum period in women at risk for pregnancy-induced hypertension (PIH).The aim of this study is to explore and describe changes in intrapersonal factors in participants at risk for PIH.We used an explorative design in which 3 questionnaires were sent by email to 110 participants the day following enrollment in the Pregnancy Remote Monitoring program for pregnant women at risk for PIH. Women were invited to complete the questionnaires at the beginning of their participation in the Pregnancy Remote Monitoring project (mostly at 14 weeks of gestation) and after approaching 32 weeks of gestational age (GA). The Generalized Anxiety Disorder-7 Scale (GAD-7) and the Patient Health Questionnaire-9 were used to assess anxiety and depression, and adaptation of the Pain Catastrophizing Scale was used to measure trait pain catastrophizing.P=.01; and Patient Health Questionnaire-9 score=6, range 4-10 vs 4, range 2-7; P<.001). The subscale scores of the Pain Catastrophizing Scale were all lower at 32 weeks of GA compared with 14 weeks of GA . The proportion of women with a risk for depression (GAD-7 score >10) was 13.3% (10/75) at enrollment and had increased to 35.6% (26/75) at 32 weeks of GA.Scores were significantly higher at 32 weeks of GA than at the moment of enrollment (GAD-7 score=7, range 4-11 vs 5, range 3-8; This study shows that pregnant women at risk for PIH have higher levels of stress and anxiety at 32 weeks of GA than at the moment of enrollment. Further research is recommended to investigate potential strategies to help pregnant women at risk for PIH manage feelings of stress and anxiety.ClinicalTrials.gov NCT03246737; https://clinicaltrials.gov/study/NCT03246737 The peripartum period, defined as the period from the beginning of gestation until 1 year after delivery, has long been shown to be potentially associated with increased levels of stress and anxiety with regard to one’s transition to the status of parent and the accompanying parental tasks . ElevateA medically high-risk pregnancy is defined as “any pregnancy in which there is evidence of an actual or potential threat of harm to the life or health of the mother or the baby because of a disorder or situation coincidental with or unique to pregnancy” . Health Pregnancy-induced hypertension (PIH) complicates between 6% and 10% of all pregnancies and can turn a low-risk pregnancy into a high-risk pregnancy. It is defined as an in-office measurement with a systolic blood pressure (BP) above 140 mm Hg and a diastolic BP above 90 mm Hg. Severe range BP is above 160 mm Hg systolic and 110 mm Hg diastolic. PIH refers to one of four conditions: (1) preexisting hypertension, (2) gestational hypertension, (3) preeclampsia, and (4) unclassified hypertension. PIH is one of the leading causes of maternal morbidity and mortality. Hypertensive disorders may result in fetal complications such as growth restriction, oligohydramnios, placental abruption, preterm birth, and perinatal death ,24. The New techniques to support these strategies have recently been developed, including remote monitoring (RM), which can broadly be defined as the use of telecommunication technologies to facilitate the transmission of medical information and services between health care providers and participants . RM is aIn developing those new strategies (including RM) to optimize the obstetric care of pregnant women at risk for PIH, it is important to investigate patient characteristics and intrapersonal factors. To the best of our knowledge, no research to date has been conducted about changes in the intrapersonal factors during the peripartum period in women at risk for PIH. Therefore, the primary aim of this study was to explore potential changes in anxiety and depression during pregnancy, from the moment of enrollment in the PREMOM I study  to 32 weeks of GA. Our hypothesis was that anxiety and depression would have increased by 32 weeks of GA compared to the moment of enrollment due to the fact that delivery and associated complications are imminent. The secondary aim of this study was to study the level of catastrophizing at both measurement moments. We hypothesized that the levels of catastrophizing would increase between the inclusion enrollment and 32 weeks of GA due to pregnancy-related symptoms.The PREMOM I study was set up in January 2015 as a collaboration in Belgium between Hasselt University, Ziekenhuis Oost-Limburg (Genk), and 7 other hospitals . Women who participated in the PREMOM I study received obstetric surveillance through a BP monitor, an activity tracker, and a weight scale. They were asked to perform 2 BP measurements each day (morning and evening), to wear the activity tracker continuously, and to register their weight once a week in the app. This information was to be recorded until the moment of their delivery or until they were admitted to the hospital. The data collected using these devices were transferred to a web-based dashboard developed by the Mobile Health Unit . Predefined alarm signals were developed. Alarm signals were communicated to the responsible obstetrician so that treatment options could be agreed upon with the midwife before the pregnant woman was contacted. The therapeutic interventions were in line with local treatment procedures. The workflow is summarized in In the past few years, our research team has published several articles related to the PREMOM I study that demonstrated the benefit of RM for pregnant women at elevated risk of developing PIH. Two articles made comparisons between women who received RM and women who had an increased risk of developing PIH but did not participate in the PREMOM I study  based on a retrospective and observational design. In both studies, prenatal hospitalization to a prenatal ward (until the moment of delivery), diagnosis of preeclampsia, and number of inductions were reduced in the RM group compared with the CG. However, women in the RM group had significantly higher risks of developing gestational hypertension and a spontaneous start of the birth process compared with the CG. In the study conducted in 2015, the total number of neonatal hospitalizations in the neonatal intensive care unit was lower in the RM group than in the CG group; these findings were not confirmed in the study conducted in 2015-2016. In the later study, the total number of prenatal visits was lower in the RM group than in the CG group; this difference was not apparent in the earlier study -35.The process of patient enrollment is shown in For this study, an explorative and descriptive quantitative design was used. Pregnant women were given written information about the study when they received their BP monitor and activity tracker at the start of their RM program. The following day, all participants received an email containing a SurveyMonkey link. After logging in, the participants were asked to complete 3 questionnaires (see subsection Questionnaires) at 2 moments in time: the day following their enrollment in the RM program and at 32 weeks of GA. Demographic and obstetric characteristics of the participants were collected at the moment of enrollment in the PREMOM program and after delivery, through the hospital administration or billing records.The Generalized Anxiety Disorder-7 scale (GAD-7) was used to detect anxiety disorders. The GAD-7 was developed within the classical theory as a brief, dimensional screening instrument that aims at identifying probable cases of anxiety disorder and also assessing symptom severity . Simpsont tests (parametric) or Mann-Whitney U tests (nonparametric) were used for between-group comparisons. Both dimensional and categorical analyses were performed. For the PCS, catastrophizing was dichotomized as described by Olsson et al [P values <.05 were considered statistically significant.Data analysis was performed using R statistical software . No data imputation was performed for missing data. The study sample size was based on an a priori sample size calculation with a power of minimum 70 participants. The Shapiro-Wilk test was used to assess whether or not the data were normally distributed. Nonparametric tests were used in case where the normality assumption was violated. Skewed data are expressed as a median and IQR. Independent on et al . The 2 cThe study was approved by the Ethical Committee of the Ziekenhuis Oost-Limburg (15/093U - B371201526777) and all participants provided written informed consent. The study was also registered at ClinicalTrails.gov (NCT03246737).In total, 75 participants completed all questionnaires at both time points. Patient mean age was 30 (28.0-32.5) years, and 28 (37.3%) of the women were pregnant for the first time. P=.01 at the moment of enrollment; and PHQ-9 score=6, range 4-11 at 32 weeks of GA; and 4, range 2-7; P<.001 at the moment of enrollment). Only magnification was significantly lower at 32 weeks of GA compared to the moment of enrollment .The results  showed tIn Based on the PCS, 25 (33.33%) pregnant women of the 75 crossed the cutoff value of more than 17 for the total sum described by Olsson et al  at the tWe sought to explore and describe potential changes in some intrapersonal factors of participants at risk for PIH. To the best of our knowledge, this is the first publication targeting this change in psychological factors during pregnancies at risk of this complication. Two interesting sets of findings emerged.First, in line with our expectations, scores on the GAD-7 and PHQ-9 were higher at 32 weeks of GA compared to the moment of enrollment. The scores on the subscales of the PCS were all lower at 32 weeks of GA compared with 14 weeks of GA. Regarding the primary end point (higher score for anxiety and depression at 32 weeks compared to 14 weeks), this hypothesis can be adapted. This study showed that pregnant women with PIH followed a normal pattern of increased pregnancy scores, as described by Biaggi et al . The proRegarding the second research aim of this study, catastrophizing in women included in this study decreased significantly for the subscale “magnification,” but was relatively stable for the subscales “rumination” and “helplessness,” and for the categorical approach. This is in line with the reported stability of catastrophizing over time during a normative pregnancy . HoweverFor the GAD-7, Zhong et al  reportedAt 16 weeks of GA, 13.71% (159/1160) of the study population in the study of Avalos et al  were diaAt both 14 weeks of GA and at 32 weeks of GA, 33.3% (25/75) of participants reported catastrophizing; 4% (3/75) of this catastrophizing was found clinically depressed at enrollment, compared to 5.33% (4/75) at 32 weeks of GA. These numbers are higher than the 27.75% (72/242) of women who catastrophize at 19-21 weeks of GA and the 30.16% (73/242) of catastrophizing women at 34-37 weeks of GA reported by Olsson et al .Our study is the first to show a significant change in psychological factors during pregnancies at risk for PIH. These results indicate a need for additional psychological support during pregnancies with this kind of complication.Although the results of this study are promising, there are a number of limitations that should be considered. First, the generalizability of the results may be limited by the single-center design of the study. Second, the study results relied on self-reported data only. To complement the questionnaire data, clinical diagnostic interviews are required. Aside from circumventing shared method variance, this could have the additional advantage of offering the possibility to determine whether the study participants think the symptoms are pregnancy-related ,49, as sIt is known that depression rates tend to increase with each trimester, and the risk of generalized anxiety disorder and pain interference significantly increases over time during the third trimester ,42,50. IThe peripartum period has long been known to be associated with increased levels of stress and anxiety, which can be exacerbated by PIH. This study shows that pregnant women at risk for PIH have higher scores on the GAD-7 and PHQ-9 at 32 weeks of GA, compared to the moment of enrollment. The subscale scores of the PCS were all lower at 32 weeks of GA compared with 14 weeks of GA. Further research is recommended to explore if the GAD-7, PHQ-9, and PCS scores of these pregnant women with PIH at the moment of enrollment and at 32 weeks of GA are significantly lower or higher compared to women with a no- or low-risk pregnancy. The knowledge that follows from this research can help implement strategies to manage pregnant women at risk for PIH with their feelings of stress and anxiety.


In the presented study, we have synthesized six nanocomposites based on various magnetic nanoparticles and a conducting polymer, poly (P3HT). Nanoparticles were either coated with squalene and dodecanoic acid or with P3HT. The cores of the nanoparticles were made of one of three different ferrites: nickel ferrite, cobalt ferrite, or magnetite. All synthesized nanoparticles had average diameters below 10 nm, with magnetic saturation at 300 K varying between 20 to 80 emu/g, depending on the used material. Different magnetic fillers allowed for exploring their impact on the conducting properties of the materials, and most importantly, allowed for studying the influence of the shell on the final electromagnetic properties of the nanocomposite. The conduction mechanism was well defined with the help of the variable range hopping model, and a possible mechanism of electrical conduction was proposed. Finally, the observed negative magnetoresistance of up to 5.5% at 180 K, and up to 1.6% at room temperature, was measured and discussed. Thoroughly described results show the role of the interface in the complex materials, as well as clarify room for improvement of the well-known magnetoelectric materials. Having both electrical properties and magnetic response, with addition of possible flexibility and ease of synthesis, nanocomposites based on conducting polymers and magnetic nanoparticles are of high interest both in the scientific and commercial worlds ,2. ContiAmong many interesting and adjustable properties of such composite materials, the alteration of their properties under the influence of the magnetic field (magnetic field effects—MFE) is of high interest. The influence of the magnetic field was observed to have an impact on the photocurrent (magneto-photocurrent) ,10, elecAmong other MFEs, one that is constantly drawing attention to the polymer-magnetic nanoparticle composites is magnetoresistance (MR). It is described as the alteration of the electrical resistivity (R) of the material in the external magnetic field (H).The positive MR is seen as the increase, while the negative MR results in the decrease of the resistivity in the external magnetic field. The use of magnetic semiconducting nanoparticles allows for tuning the conductivity of the material ,18. ThanThis study presents the synthesis of six different core–shell nanoparticles which are later suspended in the electrically conductive polymer matrix to obtain nanocomposites with magnetoelectric properties. The shell of the nanoparticle, made of either insulating material  or conducting material ), covers a magnetic core made of one of three different ferrites. The morphology and magnetic properties of the nanoparticles are thoroughly analyzed to help understand the differences between the obtained nanoparticles. Finally, the electrical and magnetoresistive properties of thin composite films made of nanoparticles suspended in P3HT are carefully studied to establish the influence of the shell-covering nanoparticle on the conductivity mechanism.3 (acac = acetylacetonate) (97%), Ni(acac)2 (97%), Co(acac)2 (97%), dibenzyl ether (98%), squalene (95%), dodecanoic acid (98%), and anhydrous dichlorobenzene were purchased from Sigma Aldrich. Poly (P3HT) Mw = 51,000 u and over 90% regioregularity was purchased from Rieke Metals. All reagents were used as received.Fe(acac)3O4 nanoparticles (Fe(Sq)) was based on the thermal decomposition of the acetylacetonates in a controlled argon gas atmosphere, thoroughly described in our previous work [The synthesis of the Feous work . The synThe synthesis of magnetite nanoparticles capped with P3HT (Fe(P3HT)) was already described in our previous work . The synNanoparticles obtained following the previously described procedures (NP(Sq) for nanoparticles capped with squalene and NP(P3HT) for nanoparticles covered with P3HT) were suspended in P3HT dissolved in dichlorobenzene. The concentration of polymer was set to 14 mg/mL and nanoparticles to 10 mg/mL. The solutions were put in the ultrasonic bath for one hour to ensure good distribution of the nanoparticles in the polymer solution. Six different prepared solutions were further used to obtain nanocomposite films.For the magnetic characterization of obtained nanoparticles, a vibrating sample magnetometer (VSM), type 7407 Lake Shore Cryotronics, Inc.,  was chosen. Before the measurement, the nanoparticles were dried, and as a powder transferred to the apparatus in a Teflon vessel. All measurements were conducted at three temperatures: low (80 or 100 K), nearly room temperature (290 or 300 K), and high (440 K), in an external magnetic field ranging from –1500 mT to 1500 mT.2 wafer/substrate. The distance between electrodes was set to 75 µm.Substrates for the conductivity measurements were custom made. They consisted of two 100 nm thick gold electrodes evaporated on top of the SiO2 ≤ 0.1 ppm and H2O ≤ 0.1 ppm). The samples were annealed at 130 °C for 15 min and left overnight to cool down. Afterward, the contact pads were cleaned with a cleanroom swab dipped in dichlorobenzene. Samples were transferred in the isolated sample holder to the VSM apparatus equipped with a conductivity measurement holder. The continuous nitrogen gas flow in the apparatus ensured the elimination of the oxygen and humidity in the vicinity of the sample. Conductivity measurements were carried out using the two-point method with a Keithley 2400 source meter. The distance between the electrodes was set to 75 µm. The R(T) characteristics were collected at different temperatures ranging from 200 K to 400 K.Nanocomposite solutions were drop cast on the described substrates in the argon-filled glovebox (OSamples were prepared in the same manner as for R(T) measurements. The external magnetic field was applied parallel to the sample’s surface. The magnetic field was applied in the sequence starting at 0 mT, then increasing to 1500 mT, and then changing to −1500 mT, and finishing at 0 mT with the 10 mT/s step and 5 V applied to the sample to measure the magnetoconductivity of the sample. The same measurements were conducted in the temperature regime ranging from 300 K to 200 K, all with the same sequence.. The Fe(Sq) and Co(Sq) samples are characterized by regular cubic and hexagonal shapes with ~10 nm diameter, while Fe(P3HT) samples have the same mean diameter (~10 nm) but their dispersity of size is higher. The Co(P3HT) particles are slightly smaller (~7 nm) and irregular, similar to Fe(P3HT). The most regular shapes, hence least defected structures, were obtained from the pure Fe3O4 and nanoparticles doped with cobalt in the presence of surface agents—squalene and dodecanoic acid. There is a visible distinction between nanoparticles synthesized directly in the polymer matrix and the surface agent—nanoparticles in the presence of polymer become more irregular and smaller. The aggregation of nickel and cobalt ferrite nanoparticles is similar, but pure Fe3O4 nanoparticles synthesized in the presence of polymer are not aggregated at all. A possible explanation is that the magnetic interactions between the particles are much smaller in comparison to the Fe(Sq) or Co(Sq), which can be established during the VSM measurement. Secondly, there is a possibility the polymer coverage is stabilizing small nanoparticles. The dispersity of sizes between NP(Sq) and NP(P3HT) is similar in two out of three types of nanoparticles, which is surprising and shows that the use of size- and shape-controlling mediums during the synthesis, such as squalene and dodecanoic acid, has little effect on the distribution of sizes, but affects the regularity of obtained shapes.The morphology with the corresponding histograms of all six types of obtained nanoparticles is presented in Figure 1s) of all synthesized nanoparticles with corresponding bulk values taken from the literature are presented in s is a characteristic value of the field that aligns all of the magnetic moments in the sample. The comparison of alterations of values between the bulk and the nanoparticles allows making some assumptions about the magnetic dead layer (MDL) [s of the nanoparticle is observed for Co(P3HT) and Ni(Sq) nanoparticles, which is probably caused by the structural distortions present at the surface of the nanoparticles in the samples. Additionally, almost no difference of Ms is observed for magnetite nanoparticles, showing that the magnetic properties are similar regardless of the less regular size of Fe(P3HT) and different outer layers. The Ms of nickel nanoparticles is four times smaller than magnetite , which is a result of the highest proportion between the surface and the core. Since the surface may be treated as a defected structure, the MDL will have the biggest impact on the magnetic properties when the nanoparticles’ size is decreasing. The results for Co(P3HT) nanoparticles support this hypothesis: Co(Sq)’s Ms and the nanoparticle’s diameter are two times bigger than those of Co(P3HT). Worth pointing out is the lack of (or very low) coercivity in almost all samples (Co(Sq) in 100 K being one exception), which shows that the addition of polymer to the nanoparticles does not have a negative, insulating impact on the magnetic properties of the composite, which was observed for a similar P(VDF-H FP)/Cobalt ferrite nanocomposite [The magnetic hysteresis loops of as-received nanoparticles at three different temperatures are presented in er (MDL)  and the omposite .Next, the electrical properties of nanocomposites based on the nanoparticles described above were checked. The materials were studied without and with the magnetic field applied during the conductivity measurements.To determine the electrical conductivity mechanism of obtained nanocomposites, the resistivity of the samples was measured at temperatures ranging from 200 to 400 K. Because the resistivity is decreasing with the increase of temperature, the nanocomposites are typical semiconducting materials with a negative temperature coefficient , and n is the constant <1,3>, which reflects the dimension of the system. Mott temperature (T0) is related to the decay length of the localized wave function of the charge carriers and the DOS at the Fermi level and is also known as a hopping barrier [T0 is correlated with the disorder of the polymer [T0 increase for samples covered with P3HT. This correlation and the fact that samples follow the function trend very well suggest a quasi-3D VRH electrical conduction mechanism for the four measured samples. We believe that the hopping of the carriers may occur between P3HT covering NP(P3HT) and the polymer matrix, and at the same time, the transport may occur along the polymer backbone [In Equation (2),  barrier . The res polymer , the resbackbone ,32. On t0  and theIn conclusion, we have created six different nanocomposites, based on magnetic nanoparticles, covered with two types of shells (insulating and conducting), and an electrically conductive polymer matrix. Electrical conductivity measurements have proven a significant influence of the nanoparticles on the charge carrier transport. Results suggest a quasi-3D VRH electrical conduction mechanism for nanocomposites in which magnetite, cobalt, or nickel ferrite nanoparticles were used as fillers. Moreover, we have shown that the choice of shell-covering for the magnetic nanoparticle has a major impact on both the conduction paths in the nanocomposites and the probability of charge carrier scattering. Furthermore, we have shown higher negative magnetoresistance for nanocomposites based on nanoparticles covered with a conductive polymeric shell. We have observed the relationship between the saturation magnetization of nanoparticles and the magnetoresistance change. The highest magnetoresistance variation, of up to 5.5% at a magnetic field of 1500 mT, was measured for the nanocomposite based on the magnetite nanoparticles covered with a conductive shell. As a takeaway summary, our nanocomposites which combine electrical conductivity with a magnetic response can be used as easily made thin sensors of magnetic fields or as new scalable materials for organic spintronic applications.


In the process of specimen deformation, unstable, metastable, and stable areas of plastic deformation localization are formed and replaced, and the formation of stable areas of localized plastic deformation, in which the specimen fails at the end of the test, can be detected at the initial stages of testing. In specimens, during the test in the zone of localized plastic deformation, bands are formed which pass through the entire surface of the specimen at an angle of 35 to 55 degrees to the tensile axis, and their development leads to the formation of stable zones of localized plastic deformation and to the failure of the specimen.This paper presents the results of uniaxial tensile tests on specimens of the hypoeutectic aluminum-silicon alloy A319. According to the results, the influence of surface treatment by pulsed electron beam on the mechanical properties of the material was determined. The peculiarities of deformation localization in the material caused by grinding of the surface layer material structure due to rapid crystallization during electron beam treatment were revealed. The surface treatment up to the depth of 100 µm leads to the formation of a fine dendritic columnar structure of silumin and to an increase in the plasticity of the samples. The influence of the surface treatment affects the increase in the deformation localization in the region of the stable concentrator before failure. The greatest increase in ductility and localization of deformation occurs during treatment with an energy density of 15 J/cm Changing the surface properties of structural materials can lead to an increase in the strength or plasticity of the product as a whole. Elimination of surface layer defects, refinement of grain structure, formation of optimal structural phase composition from the point of view of plastic deformation and fracture localization peculiarities can contribute to change the plastic deformation and fracture characteristics. High-energy pulsed electron beam is one of the promising tools for modifying the surface layer of metals and alloys . As a reA number of research groups are studying the behavior of the structure, defect substructure, elemental and phase composition ,5,6,7, iSeveral studies ,11 have In works ,12 it isA brief review of modern studies of the effect of electron beam treatment on the deformation behavior of metals allows us to conclude that this issue is a promising area of research and requires further development. At the same time, it is still unknown how a change in the structure and properties of a thin surface layer of the material can contribute to a change in the characteristic features of deformation localization and fracture of the samples as a whole. Therefore, the purpose of the present work is to study the influence of pulsed electron beam surface treatment of A319 grade hypoeutectic silumin on the characteristics of its plastic deformation and fracture under tensile stress.−1, electron beam energy density 15 and 25 J/cm2. As shown in [The samples were obtained from a hypoeutectic aluminum-silicon alloy of A319 grade (Al-(4-6)Si-1.3Fe-0.5Mn-0.5Ni-0.2Ti-2.3Cu-0.8Mg-1.5Zn, wt%). Samples in the form of bilateral proportional blades with the working area dimensions of 55 mm × 9.6 mm × 3.8 mm were prepared a. The saTensile testing of the specimens was performed on an Instron 3386 testing machine at a tensile speed of 0.2 mm per minute. The test scheme is shown in yy—along the Y axis, axis directed along the applied stress), transverse deformation  were determined and analyzed [Measurements of the development of deformation fields on the surface of the investigated specimens were carried out using the VicSnap program on the basis of the obtained synchronous recording of images from two cameras c. As a ranalyzed ,20. The Electron beam treatment of the surface causes rapid melting of the surface layer and subsequent crystallization at a sufficiently high rate. This results in the refinement of the alloy structure in the thin surface layer and the formation of a peculiar morphology on the surface. This, in turn, determines the characteristics of deformation and fracture of the material during testing. yy>  of untreated specimens and specimens treated with 15 and 25 J/cm2 electron beam energy density (ES).The plastic deformation of the specimens under test is fairly uniform until ultimate strength and fracture are reached. 2 increased by 55%, and with ES = 25 J/cm2 by 27%. The maximum relative strains of the untreated specimen were 0.234%, at ES = 25 J/cm2 were 0.297%, and at ES = 15 J/cm2 were 0.363%. The Young’s modulus of the untreated and electron beam-treated samples at ES = 25 J/cm2 is the same and is equal to 60 GPa, and at ES = 15 J/cm2 it decreases by 3.3% and is equal to 58 GPa. The tangent modulus of deformation at the point of failure of the specimen without treatment was 15 GPa. For the specimens treated with ES = 15 J/cm2 and 25 J/cm2, it decreased by 47 and 27%, respectively, which is equal to 8 and 11 GPa.Electron beam treatment of the surface does not result in significant changes in tensile strength. The maximum stress before failure of the specimens varies within 4%. However, analysis of the change in strain of the specimens during the test shows that the plasticity of the specimens changes quite significantly. Maximum relative strains of specimens treated by pulsed electron beam with energy density 15 J/cmThe increase in plasticity of samples treated by pulsed electron beam is caused by a significant change in the structure of the surface layer of silumin. The conducted studies show that in the cast state the structure of silumin A319 is represented by dendrites of solid solution based on aluminum, Al-Si eutectics, inclusions of silicon and needle-shaped intermetallides, which is clearly marked on the fracture surface a. The de2  was used to determine the overall deformed state of the specimen along the edges of the work area. Since the stress-strain diagram  over the sample surface (relative to the raw sample). The increase in plasticity (+27%) of silumin samples at electron beam treatment with energy density 25 J/cm2 due to both increased values of maximum longitudinal deformations <εyy> (+17%) and increased values of minimum deformations (+10%) across the sample surface (relative to the raw sample without treatment).The increase in plasticity (+55%) of silumin samples at electron beam treatment with energy density 15 J/cmxx> on a surface of silumin sample without treatment made 0.282%; at energy density ES = 15 J/cm2 values of deformations have increased on 89% and are equal to 0.535%; at energy density ES = 25 J/cm2 values of deformations have increased on 5% and are equal to 0.296%. The increase in ductility (+55%) of silumin specimens at electron beam treatment with energy density ES = 15 J/cm2 is due both to high values of maximum transverse strains <εxx> (+89%) along the specimen surface (in comparison with the starting specimen) and to increased values of minimum strains (+82%) along the specimen surface . The smaller increase in ductility (+27%) of silumin specimens at electron beam treatment with energy density ES = 25 J/cm2 is due to both smaller increase in values of maximum transverse deformations <εxx> (+5%) and smaller increase in values of minimum deformations (+23%) over the specimen surface (in comparison with the raw specimen).Values of maximum transverse deformations <ε2. However, the greatest ductility is characteristic of the specimens treated with an electron beam with an energy of 15 J/cm2.The conducted studies show that by treating the surface of hypoeutectic aluminum alloy A319 with pulsed electron beam it is possible to form in the surface layer a structure of the fine dendritic cell (columnar) type without inclusion of secondary phases of needle (lamellar) shape, which leads to a significant increase in plasticity of the material with a small change in strength properties. The depth of the treated zone varies from 15 to 100 μm. The greatest depth of the surface layer is characteristic of samples treated at 25 J/cm2, while the deformation bands are most pronounced in specimens treated with energy 25 J/cm2. Plastic deformation localization zones can be of stable, metastable, and unstable types. Zones of the first type form from small amounts of deformation and develop throughout the test. Zones of the second type may develop over a long period of time, but their effects then diminish or cease. Third type zones form for a short period of time and then disappear. The fracture structure of the base metal of treated and untreated specimens is represented by brittle chipping along the boundaries of the silicon inclusions. The destruction of the treated surface layer is characterized by intergranular fracture along the boundaries of columnar dendrite arms.The obtained data testify to the localization of deformation in all types of specimens during testing. This process begins with the formation of a chaotic or staggered distribution of localized areas of plastic deformation. Further development of the plastic flow leads to the formation of deformation bands from individual concentrators located at an angle of 45 degrees to the deformation axis. Bands of two orientations intersecting each other are present in the specimens. Areas of maximum localization of plastic deformation are formed at the intersection of such bands. The tendency to band formation increases after surface treatment with electron beam, and the deformation localization is maximum in specimens treated with electron beam of energy 15 J/cmThus, the results obtained demonstrate the effectiveness of electron beam surface treatment of aluminum-silicon alloys in reducing their brittleness and increasing their ductility.


In “Impact of a Postintensive Care Unit Multidisciplinary Follow-up on the Quality of Life (SUIVI-REA): Protocol for a Multicenter Randomized Controlled Trial” :e30496) the authors made three clarifications.In the sample size section of the manuscript, the passage:Therefore, we estimated that at least 50% had a very poor outcome, combining death and moderate to severe impairment of at least one EQ5D dimensionhas been corrected to:Therefore, we estimated that at least 50% had a very poor outcome, combining death and severe to extreme impairment of at least one EQ5D dimension.In the sample size section of the manuscript, the passage:The study was then powered to detect a decrease from 50% to 37% of patients with very unfavorable outcome with a power of 90% and a 2-sided 5% alpha risk, assuming this rate would be 50% in the control arm.has been corrected to:The study was then powered to detect a decrease from 50% to 37% of patients with very unfavorable outcome with a power of 80% and a 2-sided 5% alpha risk, assuming this rate would be 50% in the control arm.In the “statistical methods” section of the manuscript, the passage:The 1-year survival rate without major deterioration in QoL  will be compared between both arms using a piecewise exponential model considering any censorship and the repeated nature of observations, prohibiting the use of conventional methods of analysis of censored datahas been corrected to:The 1-year survival rate without major deterioration in QoL  will be compared between both arms using a piecewise exponential model considering any censorship and the repeated nature of observations, prohibiting the use of conventional methods of analysis of censored data.The correction will appear in the online version of the paper on the JMIR Publications website on April 14, 2023, together with the publication of this correction notice. Because this was made after submission to PubMed, PubMed Central, and other full-text repositories, the corrected article has also been resubmitted to those repositories.


Thus, analysis of the influence of demographic factors described by the age structure and gender breakdown of the population over the course of the COVID-19 pandemic was performed. This allowed the identification of local anomalies in the course of the COVID-19 pandemic. Analyses were carried out for the area of Poland. The results obtained may be useful for local authorities in developing strategies to further counter the pandemic.A growing number of various studies focusing on different aspects of the COVID-19 pandemic are emerging as the pandemic continues. Three variables that are most commonly used to describe the course of the COVID-19 pandemic worldwide are the number of confirmed SARS-CoV-2 cases, the number of confirmed COVID-19 deaths, and the number of COVID-19 vaccine doses administered. In this paper, using the multiscale geographically weighted regression, an analysis of the interrelationships between the number of confirmed SARS-CoV-2 cases, the number of confirmed COVID-19 deaths, and the number of COVID-19 vaccine doses administered were conducted. Furthermore, using maps of the local R The COVID-19 pandemic became one of the major health challenges of the 21st century and has changed the world today. The pandemic has inflicted almost unimaginable harm on the life, health, and economy of many nations [The available scientific databases are particularly full of studies on the impact of the COVID-19 pandemic on human health ,9,10,11.The issue of the COVID-19 vaccine has become a basis of the research carried out by various scientists ,27,28,29One consequence of the COVID-19 pandemic was also an increase in mortality ,38. SpecThe studies related to the COVID-19 pandemic also address the impact of the pandemic on many aspects of human life. The pandemic has changed the perception of green spaces in cities ,48,49,50Analysis of the interrelationships between the three variables that are most commonly used to describe the course of the COVID-19 pandemic worldwide—the number of confirmed COVID-19 deaths, the number of COVID-19 vaccine doses administered, and the number of confirmed SARS-CoV-2 cases.Analysis of the influence of demographic factors described by the age structure and gender breakdown of the population over the course of the COVID-19 pandemic.Identification of the local anomalies over the course of the COVID-19 pandemic.Worldwide studies have reported that the COVID-19 pandemic has a varying course in different areas in different countries ,58,59,60p-values. Only after rejecting the null hypothesis was it possible to accomplish research objectives #1 and #2, using multiscale geographically weighted regression (MGWR) by comparing R2 indices. Next, research objective #3 was accomplished, again using MGWR, but by comparing maps of local R2 estimates. The final step of the analysis was to examine the validity of the applied regression model by testing the level of autocorrelation of the residuals in the model, using the spatial autocorrelation tool , and by evaluating z-score indices. To summarize and outline the research process and accompanying research methods, these elements are presented in the graph in The first step in the research process was to determine the statistical significance of the analyzed variables using the null hypothesis. This step was accomplished using the spatial autocorrelation tool , by evaluating the Fulfillment of the above research process and the results obtained from the analyses may be useful for local authorities in developing strategies to further counter the pandemic.Analysis of the interrelation between the number of confirmed SARS-CoV-2 cases, the number of confirmed COVID-19 deaths, and the number of COVID-19 vaccine doses administered, as well as analysis of the influence of demographic factors described by the age structure and gender breakdown of the population over the course of the COVID-19 pandemic, were carried out for the territory of Poland.In terms of administrative division, the territory of Poland is divided into three levels: voivodships, counties, and municipalities. The first level (‘voivodships’) is the largest in the area and represents large regions; the third level  is the smallest in the area and represents towns or rural areas. The second level, the county level, is the most detailed level for which data over the course of the COVID-19 pandemic have been published in Poland: the number of confirmed SARS-CoV-2 cases, the number of confirmed COVID-19 deaths, and the number of COVID-19 vaccine doses administered. For this reason, and because of the high precision of the analysis based on the level of the county, this level was chosen for further study. Poland is divided into 380 counties with an average area of approximately 822 square kilometers (with a standard deviation of 520.55); a high number of analyzed counties is advantageous in this because the chosen regression model requires a large amount of data to achieve the best results . Figure Three variables that are most commonly used to describe the course of the COVID-19 pandemic worldwide were obtained from the database published by Michal Rogalski and Konrad Kalemba ,63, compThe first vaccine against COVID-19 was administered in Poland at the end of 2020. Initially, medical personnel and others at high risk of exposure to the virus were vaccinated. In 2021, the vaccination program covered all citizens of the country, regardless of age, occupation, and exposure to the virus. The year 2021 was the most challenging year of the COVID-19 pandemic in Poland, due to the high number of cases, as well as the frequent lockdowns ,75. For In order to study the influence of the demographic factors described by the age structure of the population over the course of the COVID-19 pandemic, accurate demographic data were obtained for the year 2021, for the counties of Poland. The data come from Statistics Poland, the official government statistical service for Poland. Data from this source are validated and reliable, and are used in a wide range of studies ,77,78.The first step of the research was to establish the null hypothesis: the analyzed data are not statistically significant, and the results obtained from the data are the result of random chance. To assess the likelihood of the null hypothesis being true or false, a spatial autocorrelation analysis  was carried out using ArcGIS Pro 3.1 software. Spatial autocorrelation is the presence of systematic spatial variation in a variable, the most common method to measure spatial autocorrelation is to calculate the Moran’s I index ,81,82,83i is the dependent variable of the i-th, xik is the explanatory variable of the i-th, ui and vi are the spatial coordinates of the i-th , βbwk  is the estimated coefficient of the k-th explanatory variable for the i-th with the bw bandwidth, and εi is the residual at the location .Once the null hypothesis is rejected , it was possible to conduct research using geographically weighted regression. This article uses the multiscale geographically weighted regression method (MGWR), the extended and advanced version of GWR. This spatial regression technique explores geographically varying relationships between dependent variables and explanatory variables; MGWR is being used to analyze a variety of problems in geography, urban planning, and various other disciplines ,85; studThe MGWR method can be used to estimate the effects of explanatory variables on the dependent variable, and also to identify counties in which the influence of variables differs, to explore and interpret spatial nonstationarity. Due to the complexity of the study objectives, variables V1 and V3 will be treated as both dependent and explanatory variables in subsequent analyses, while the variables V2 and V4–V15 will only be used as explanatory variables. ArcGIS Pro 3.1 software was used to perform the MGWR analysis. GIS software is widely used for spatial analysis in a large variety of scientific fields ,92,93,942 (or R-squared) index; it is the proportion of the variance of the dependent variable explained by the regression model. By comparing the values of the R2 index, it is possible to draw conclusions about the variables.The degree of influence of the explanatory variables on the dependent variable is described by the R2 values present a picture of the analyzed phenomena for the whole of Poland. This is a generalized picture that does not allow an in-depth analysis of such a complex issue as the COVID-19 pandemic. The MGWR regression model allows for the mapping of local R2 values, thus exploring spatially varying relationships between variables. Mapping local R2 estimates can provide clues about important variables that may be missing from the regression model, i.e., whether the course of the pandemic in Poland may have been influenced by other factors not included in the model.The R2 > 0.8), and a weak or insignificant level of spatial autocorrelation in the residuals [The final step in the analysis was to examine the level of autocorrelation of the residuals in the regression model. The level of autocorrelation, which indicates the nonrandom nature of the residuals indicates that the regression model is somehow biased by other factors. Spatial autocorrelation analysis  was once again performed using ArcGIS Pro 3.1 software. The explanatory variable explains the dependent variable well only if two conditions are met: a high value of the coefficient of determination  tool measures spatial autocorrelation based on feature locations and feature values, and assesses whether the expressed pattern is clustered, dispersed, or random. The graph displays the z-score values. The graph is bell-shaped, with z-score values between −1.65 and 1.65 indicating that the data are the result of random chance. Values on the left, with a z-score below −1.65, indicate a tendency of the data to be dispersed, and values on the right (z-score > 1.65) indicate a tendency of the data to form clusters.All analyzed variables are characterized by a tendency to form clusters. A complete summary of the information obtained from the spatial autocorrelation analysis is presented in p-value, all variables are statistically significant . The results allowed the rejection of the null hypothesis and to continue the study with the regression model.According to the reports, all variables tend to form clusters. Concluding from the 2 indices are shown in The next step was to analyze the interrelationships between the variables that are most commonly used to describe the course of the COVID-19 pandemic worldwide—the number of confirmed COVID-19 deaths, the number of COVID-19 vaccine doses administered, and the number of confirmed SARS-CoV-2 cases , as well as to analyze the influence of demographic factors described by the age structure and gender breakdown of the population over the course of the COVID-19 pandemic. The stated research objectives were realized using the MGWR regression model, in ArcGIS Pro 3.1 by Esri, and the results of the R2 value among the relations of the first research objective . The relations: V3→V1, which describes the effect of the number of confirmed SARS-CoV-2 cases on the number of registered deaths as a result of COVID-19, and V2→V3, denoting the effect of the number of COVID-19 vaccine doses administered on the number of confirmed SARS-CoV-2 cases, both showed a value of 0.96. All three analyzed relationships showed very high R2 values.The V2→V1 relation, that is, the influence of the number of COVID-19 vaccine doses administered on the number of registered COVID-19 deaths, shows the lowest R2 value is 0.87 (for the V6→V2 relation). This confirms other studies showing population clusters as the most important factor in the development of the COVID-19 pandemic [2 index confirm this research by refining it to variable V6, i.e., the population in the 10–19 age range .All analyzed variables explain the dependent variables to a very high degree—the lowest Rpandemic ,97,98. Ppandemic . The res2 estimates, the third established research objective, i.e., to find local anomalies over the course of the COVID-19 pandemic, was achieved. The voivodships in Poland do not have full autonomy, but possess a certain degree of administrative independence, including decision-making and resource allocation. By superimposing the boundaries of the voivodships on the maps of the local R2 estimates, it is possible to additionally examine the influence of the voivodship governments on the analyzed phenomena.Using maps of local R2 values for Polish counties are shown in In order to thoroughly examine such a complex phenomenon as the COVID-19 pandemic, the two variables V1 and V3 were treated as both explanatory and dependent variables. The local R2 value that differs significantly from the R2 value for the country as a whole. Analyzing the spatial distribution of counties in specific classes in relation to the overlapping voivodship boundaries, there is a great deal of similarity in the V2→V1 relationship—often voivodship boundaries coincide with class boundaries. For the second V3→V1 relationship, the extent to which the explanatory variable V3 explains the dependent variable V1 was analyzed. The northern part of Masovian Voivodship (primarily Ostrołęka County), the eastern part of West Pomeranian Voivodship, the southwestern part of Lower Silesian Voivodship, as well as the boundary counties of Lesser Poland and Subcarpathian Voivodships can be considered as anomalies, i.e., areas with a local R2 value significantly lower than the R2 value for the whole country. The last V2→V3 relationship gave very uniform results of local R2 values. The exception is the counties of Subcarpathian Voivodship, where there is a cluster of counties assigned to the lowest class of 0.00–0.40, and also none of the counties is in the highest class of 0.91–1.00.The first relationship V2→V1 indicates to what extent the explanatory variable V2 explains the dependent variable V1. In the case of this relationship, the northwestern part of the Masovian Voivodship, almost the entire area of the Subcarpathian Voivodship, and the eastern part of the West Pomeranian Voivodship can be considered as anomalies, i.e., areas with a local R2 values with age ranges. The values of local R2 for the counties of Poland, explaining the variable V1 “the number of confirmed COVID-19 deaths”, are shown in The next step was to analyze deviations and anomalies in terms of local R2 values, nor does the map for the total population. In these maps, the local R2 values for counties are mainly contained in two contiguous classes, with minor deviations representing individual counties.The five population maps for the 10–19 age range and in the 40–79 age range show no clear anomalies in local RThe largest anomalies appear on the map of the 20–29 age range. This is especially noticeable in the north of the Masovian Voivodship (Ostrołęka and Przasnysz Counties), and in the bordering counties of the Lesser Poland and Subcarpathian Voivodships (mainly Gorlice County). Slightly lesser, but also noticeable deviations occur in the eastern part of the West Pomeranian Voivodship, the southeastern part of the Greater Poland Voivodship, and the eastern part of the Masovian Voivodship.Anomalies of lesser intensity can be observed in other age ranges of the population. The map of the 0–9 population  shows similar relations to the 20–29. The largest anomaly is Koszalin County, located in the eastern part of the West Pomeranian Voivodeship. Slightly smaller anomalies are found in the eastern part of Greater Poland Voivodship, the northwestern and southern parts of Masovian Voivodship, a large area of Holy Cross Voivodship, and the bordering counties of Lesser Poland and Subcarpathian Voivodship. On the population map 30–39, anomalies can again be seen in the north and west of the Masovian Voivodship, the eastern part of West Pomeranian Voivodship, and the eastern part of Greater Poland Voivodship. In the oldest age range, population over 80, anomalies again appear in the north of Masovian Voivodship, the eastern part of West Pomeranian Voivodship, and the adjacent counties of Lesser Poland and Subcarpathian Voivodship; additionally, anomalies can be seen in the bordering counties of Warmian-Masurian and Podlaskie Voivodships, the western part of Lower Silesian Voivodship, and the central-eastern part of Opole Voivodship.2 for the counties of Poland, explaining the variable V2 “the number of COVID-19 vaccine doses administered”, are shown in The values of local R2 values for the counties are in two adjacent classes.Three population maps in the 0–9, 30–39, and 40–49 ranges, as well as the total population show no counties with anomalies. In these maps, the local RAgain, the largest anomalies appear on the map of the 20–29 age range. Anomalies are clearly visible in the southeastern part of the country  and on the borders of the Greater Poland and Kuyavian-Pomeranian Voivodships.2 maps. It covers the entire area of the Subcarpathian Voivodship, as well as individual surrounding counties in the Lublin and Holy Cross Voivodships. In addition, the map of the 10–19 age range shows a large concentration of counties with anomalies, covering the central-northern part of Greater Poland province, along with adjacent counties of Lubusz, West Pomeranian, Pomeranian, and Kuyavian-Pomeranian Voivodships. Gender breakdown maps show almost no anomalies.There is a clearly visible anomaly in the southeastern part of the country, which is repeatable for the rest of the local R2 for the counties of Poland, explaining the variable V3 “the number of confirmed SARS-CoV-2 cases”, are shown in The values of local RThe four population maps in the 30–39, 40–49, 70–79, and over 80 ranges do not show any counties with clear anomalies. 2 maps for the variables V1 and V2, the largest anomalies are observed in the map of the age range 20–29. This is most evident in the counties on the Subcarpathian and Lesser Poland Voivodship boundaries (primarily Gorlice county). Such a situation also occurs in the north and west of Masovian Voivodship , the eastern part of Masovian Voivodship (Łosice County), the southeastern part of Greater Poland Voivodship, and the southeastern part of West Pomeranian Voivodship (mainly Wałcz County).As in the case of the local R2 , where anomalies are found in the same counties, only showing lower intensity.Similar relations can be seen on the map of the 10–19 age range, where the areas with the largest anomalies occur in the same locations. Similar conclusions can be drawn for the other maps of the local RThe occurrence of residual spatial autocorrelation was analyzed to assess the performance of the MGWR regression model. The spatial autocorrelation tool  was again used to measure residual spatial autocorrelation. The results are shown in Considering the z-scores, the distribution of the residuals does not appear to be significantly different from random. Out of the 39 relations, only 6 values indicating a weak dispersed pattern were registered (z-score ranging from −1.91 to −1.68). These results indicate the random nature of the residuals and confirm the validity of the MGWR regression model.2 values obtained confirm other studies showing population clusters as the most important factor in the development of the COVID-19 pandemic.Previous research by the authors has shown a lesser influence of Poland’s younger population on the spread of the pandemic in Poland , which h2 makes it possible to identify the age ranges that deviate most from the picture of the country’s demography. In the case studied in the article, this is noticeable in the 20–29 age range . For the dependent variable V2, these are the counties of Wałbrzych and Walbrzych City (located in Lower Silesia Voivodeship) and the county of Wieluń (Łódź Voivodship). For the dependent variable V3, a large group of representative counties located in the western part of the West Pomeranian region can be noted. These are the counties of Stargard, Świnoujście, Pyrzyce, Gryfino, Szczecin City, Police, Kamień Pomorski, Myślibórz, and Goleniów. In addition, the representative county of this variable is Kazimierski County, located in Holy Cross Province. Representative counties, due to minimal deviations in R2 values, can be taken as a marker or determinant of the pandemic situation nationwide. The selection of representative counties can be useful for assessing the impact of pandemic control activities. The location of the counties discussed is depicted in The conducted analyses also identify areas with the largest deviations from the picture of the country as a whole in all age groups and for all explanatory variables, as well as areas that can be identified as representative of the country in terms of local R2 = 0.93), which may indicate the impact of other variables on the dependent variable. Therefore, it can be concluded that other nondemographic phenomena not included in this study could have influenced the level of vaccination in society. This could be the basis for further research to investigate the influence of cultural, social, or ideological variables over the course of the COVID-19 pandemic.The second research objective was to analyze the impact of demographic aspects over the course of the COVID-19 pandemic. The demographic aspects were described by variables V4–V15 representing the structure of the population; the course of the COVID-19 pandemic was described by three variables—the number of confirmed COVID-19 deaths, the number of COVID-19 vaccine doses administered, and the number of confirmed SARS-CoV-2 cases. The analysis using the MGWR method showed the smallest influence of demographic aspects on the V2 variable “the number of COVID-19 vaccine doses administered”. The regression model explains the V2 variable by approx. 93% (R