Recommendations For Monitoring Research Articles

The effect of anti-tuberculosis drug pharmacokinetics on QTc prolongation

Implementation of newer anti-tuberculosis (TB) drugs may prolong the QT interval, increasing the risk of arrythmias and sudden cardiac death. The potential for cardiac adverse events has prompted recommendations for frequent cardiac monitoring during treatment. However, unknowns remain, including the association between drug concentrations and QT interval. An observational prospective cohort study design was used. Patients undergoing treatment for drug-resistant TB in Georgia were assessed. Serial blood samples were collected at 4-6 weeks for pharmacokinetics. Electrocardiograms were recommended to be performed monthly. A generalized estimating equation spline model was used to investigate (1) the effect difference between bedaquiline and delamanid, (2) the cumulative effect of number of anti-TB drugs, and (3) the relationship between serum drug concentrations on QTc interval. Among 94 patients receiving either bedaquiline (n=64) or delamanid (n=30)-based treatment, most were male (82%), and the mean age was 39 years. The mean maximum QTc increase during the first six months was 37.5 ms (IQR: 17.8-56.8). Bedaquiline- and delamanid-based regimens displayed similar increased mean QTc change from baseline during drug administration (P=0.12). Increasing number of anti-TB drugs was associated with an increased QTc (P=0.01), but participants trended back towards baseline after drug discontinuation (P=0.25). A significant association between AUC, Cmin, Cmax, and increased QTc interval was found for bedaquiline (months 1-6) and levofloxacin (months 1-12). Bedaquiline- and delamanid-based regimens and increasing number of QT prolonging agents led to modest increases in the QTc interval with minimal clinical effect.

Vancomycin dosing in high-intensity continuous renal replacement therapy: A retrospective cohort study.

An inverse relationship exists between vancomycin serum concentrations and the intensity of continuous renal replacement therapy (CRRT), reflected through the dialysate flow rate (DFR). There remains a lack of evidence to guide initial vancomycin dosing in the setting of high-intensity CRRT (i.e., DFR >30 mL/kg/h). Additionally, recommendations for pharmacokinetic monitoring of vancomycin have transitioned from a trough-based to area under the curve (AUC)-based dosing strategy to optimize efficacy and safety. Therefore, an improved understanding of the impact of CRRT intensity on AUC/MIC (minimum inhibitory concentration) has the potential to enhance vancomycin dosing in this patient population. The goal of this study is to evaluate current vancomycin dosing strategies and achievement of pharmacokinetic targets in patients on high-intensity CRRT. This was a single-center, retrospective cohort study of adult critically ill patients admitted to Houston Methodist Hospital between May 2019 and October 2021 and received vancomycin therapy while on high-intensity CRRT. High-intensity CRRT was defined by a DFR that was both ≥3 L/h and >30 mL/kg/h. Depending on the initial vancomycin dosing strategy, patients were stratified into either the traditional (15 mg/kg/day) or enhanced (≥15 mg/kg/day) dosing group. The primary outcome was the percent of patients who attained steady-state AUC24 /MIC ≥400 mg*h/L at the first obtained vancomycin level in the enhanced group compared with the traditional group. A total of 125 patients were included in the final analysis, 56 in the traditional and 69 in the enhanced dosing group. The primary end point occurred in 74% and 54% of patients in the enhanced and traditional dosing groups, respectively (p = 0.029). Therapeutic vancomycin trough levels (10-20 μg/mL) were more commonly achieved in the enhanced dosing group compared with the traditional dosing group (66.7% vs. 45%, p = 0.013). As DFR rose, increasingly higher doses of vancomycin, up to 27 mg/kg/day, were required to achieve the therapeutic targets. This is the first study to evaluate the influence of variable CRRT intensities on vancomycin AUC/MIC. Our findings suggest that vancomycin doses of ≥15 mg/kg/day are needed to achieve early therapeutic targets in patients on high-intensity CRRT.

Nephrectomy for kidney tumor increases the risk of de novo arterial hypertension.

Kidney is an essential regulator of arterial blood pressure (BP) via the renin-angiotensin system. The impact of kidney surgery on BP is unclear. To evaluate the consequences of kidney surgery for renal tumor on BP. In a multicenter prospective study, we evaluated 200 patients who underwent nephrectomy for renal tumor between 2018 and 2020 at 7 departments of the UROCCR network. All patients had localized cancer without pre-existing hypertension. BP was measured the week before nephrectomy, one month and six months after nephrectomy, according to the recommendations for home blood pressure measurement. Plasmatic renin was measured one week before surgery and 6 months after surgery. The primary endpoint was the occurrence of de novo hypertension (HTN). The secondary endpoint was a clinically significant increase in BP at six months defined by an increase in systolic and / or diastolic ABP ≥10 mmHg or if medical anti-hypertensive treatment was required RESULTS AND LIMITATIONS: BP and renin measurements were available for 182 (91%) and 136 (68%) patients, respectively. We excluded from the analysis 18 patients who had undeclared HTN detected on preoperative measurements. At six months, 31 (19.2%) patients had de novo HTN and 43 (26.3%) patients had a significant increase in their BP. The type of surgery was not associated with an increased risk of HTN (21.7% PN vs 15.7% RN; p=0.59). There was no difference between plasmatic renin levels before and after surgery (18.5 vs. 16, p=0.46). In multivariable analysis, age (O.R 1.07; CI-95 1.02-1.12; p=0.03) and BMI (O.R. 1.14; CI-95 1.03-1.26; p=0.01) were the only predictors of de novo HTN. Surgical treatment of renal tumors is associated with significant changes in BP. These changes are not impacted by the type of surgery (PN vs RN). In this study we evaluated blood pressure changes after surgery for renal tumors. We found that 19% of the patients developed de novo hypertension 6 months after surgery. We feel that patients who are scheduled to undergo kidney cancer surgery should be informed of these findings and have their blood pressure closely monitored after the operation.

Geological Hazards of Housing Development of a Pliocene Terrace Land Plot in the City of Rostov-on-Don

Introduction. In Rostov-on-Don the industrial and civil construction is carried out under a number of geological hazards: soils subsiding deformations, landslides, underfloodings, suffusions. Building up the new urban districts has always led to the groundwater surge. The Pliocene terrace building conditions in the eastern part of the city are characterised by the high risk of underflooding due to the shallow groundwater, low hydraulic gradients and water permeability of soils. The data on the present state of the groundwater level is not published in the media. Based on the materials on the territory geological structure and hydrogeological conditions, as well as on the numerical hydrogeological modeling, the present paper aims to investigate the groundwater balance determining factors and to develop the geofiltration monitoring recommendations for constraining the underflooding.Materials and methods. The geological structure and hydrogeological conditions of the territory were analysed using the published reading and graphical materials, as well as the engineering and geological survey results. The aquifers’ geometrical parameters analysis and the spatial data visualisation were made by means of the QGIS geographic information system. For creating and analysing the numerical geofiltration models, the Visual Modflow software product of Aquaveo company was used.Research results. The natural and technogenic geofiltration state of the territory under investigation had been forming for many years. The study of the designed numerical hydrogeological model indicates on the high risk of local underflooding as well as defines the conditions of its spreading throughout the entire territory. The role of the ravine-gully system that drains the aquifer and constrains the underflooding has been assessed. To control the territory groundwater balance and to specify the aquifers’ parameters, the layout of the observational hydrogeological wells network has been developed. Discussion and conclusion. The existing groundwater balance is vulnerable. Building up the territory is highly likely to cause additional infiltration of technogenic water and to lead to underflooding. The territory development project should envisage the geofiltration process monitoring and groundwater draining solutions.

A Review of Circumpolar Arctic Marine Mammal Health-A Call to Action in a Time of Rapid Environmental Change.

The impacts of climate change on the health of marine mammals are increasingly being recognised. Given the rapid rate of environmental change in the Arctic, the potential ramifications on the health of marine mammals in this region are a particular concern. There are eleven endemic Arctic marine mammal species (AMMs) comprising three cetaceans, seven pinnipeds, and the polar bear (Ursus maritimus). All of these species are dependent on sea ice for survival, particularly those requiring ice for breeding. As air and water temperatures increase, additional species previously non-resident in Arctic waters are extending their ranges northward, leading to greater species overlaps and a concomitant increased risk of disease transmission. In this study, we review the literature documenting disease presence in Arctic marine mammals to understand the current causes of morbidity and mortality in these species and forecast future disease issues. Our review highlights potential pathogen occurrence in a changing Arctic environment, discussing surveillance methods for 35 specific pathogens, identifying risk factors associated with these diseases, as well as making recommendations for future monitoring for emerging pathogens. Several of the pathogens discussed have the potential to cause unusual mortality events in AMMs. Brucella, morbillivirus, influenza A virus, and Toxoplasma gondii are all of concern, particularly with the relative naivety of the immune systems of endemic Arctic species. There is a clear need for increased surveillance to understand baseline disease levels and address the gravity of the predicted impacts of climate change on marine mammal species.

Review: Failure of current digoxin monitoring for toxicity: new monitoring recommendations to maintain therapeutic levels for efficacy.

The current recommendations for monitoring digoxin, a narrow therapeutic index drug, are limited to confirming medication use or investigating suspicion of toxicity and fail our oath to do no harm. Numerous meta-analyses evaluating digoxin use consistently recommend frequent monitoring to maintain the level of 0.5 to ≤1.0 ng/ml because higher levels lead to increased morbidity and mortality without benefit. Data from the United States National Poison Control Center (2012-2020) show annual deaths due to digoxin of 18-36 compared to lithium's 1-7, and warfarin's 0-2 respectively. The latter drugs also have narrow therapeutic indexes like digoxin yet are more carefully monitored. Recognition of digoxin toxicity is impaired as levels are not being routinely checked after medications are added to a patient's regimen. In addition, providers may be using ranges to guide treatment that are no longer appropriate. It is imperative that monitoring guidelines and laboratory therapeutic levels are revised to reduce morbidity and mortality due to digoxin. In this review, we provide a comprehensive literature review of digoxin monitoring guidelines, digoxin toxicity, and evidence to support revising the ranges for serum digoxin monitoring.

Safety aspects during treatment with clozapine. : Monitoring and rechallenge - a narrative review

Due to its unique efficacy in treatment-resistant schizophrenia, discontinuation of treatment with clozapine is frequently associated with asignificant worsening of symptoms, but also with an increased risk of suicide. Based on the literature, this review aims at summarizing different monitoring recommendations in order to be able to continue this therapy despite the occurrence of side effects. In addition, we provide recommendations when rechallenge of apreviously stopped treatment with clozapine can be considered and when adefinite discontinuation must take place. Medline, the Guideline for the use of clozapine 2013 of the Netherlands Clozapine Collaboration Group, and the S3Guideline for Schizophrenia of the German Association of Psychiatry, Psychotherapy and Psychosomatics were searched for relevant literature, the last query dating from April28th, 2023. If agranulocytosis or cardiomyopathy develops, treatment with clozapine must be discontinued and should not be resumed thereafter. In contrast, treatment with clozapine which had to be discontinued due to myocarditis or prolongation of the QTc interval may be continued if left ventricular function is normal or after normalization of the QTc interval. Other side effects are usually not absolute contraindications for rechallenge but often require the adjunctive use of additional pharmacologic and non-pharmacologic measures. Taking into consideration various monitoring recommendations, cessation of treatment with clozapine can often be prevented or treatment with clozapine that has been discontinued due to side effects can be resumed.

The Urgency of Legislative Measurements Regarding Monitoring of Toshakhana Pakistan

Toshakhana is a government-owned department administered by the cabinet division of Pakistan, has become a contentious issue in the recent decade due to the perception that it is used as a tool for corruption and for making assets by the state functionaries and also having uncertainty in its procedural laws. The masses are unlettered about the concept of Toshakhana which leads to controversies amongst the subjects of the state. The current study looked into its basic concept, regulations and procedural management. It also analyzed defects and misappropriations of valuable items by the state functionaries. Data was collected from secondary sources like existing rules, regulations, E-papers, talk shows and news on different channels and processed through qualitative research analysis. The lack of exclusive procedural laws on this subject and poor implementation of prevailing rules came out as the main conclusion and also led to drawing recommendations for adequate monitoring and management of Toshakhana.

Practices, knowledge, and attitudes about lithium treatment: Results of online surveys completed by clinicians and lithium-treated patients

BackgroundLithium remains the gold-standard medication for acute and prophylactic treatment of bipolar disorder. Understanding clinicians' practices and patients’ experiences, knowledge and attitudes about lithium may improve its clinical use. MethodsOnline anonymous surveys collected information about clinician's practices and level of confidence in managing lithium and patients' experiences with lithium treatment and information received about benefits and side effects. Knowledge and attitudes regarding lithium were assessed with the Lithium Knowledge Test (LKT) and the Lithium Attitudes Questionnaire (LAQ). ResultsAmong 201 clinicians, 64.2% endorsed often treating patients with lithium and reported high levels of confidence in assessing and managing lithium. Practices concerning clinical indications, drug titration, and serum levels were guideline-concordant, but compliance with monitoring recommendations was less frequent. Practitioners were interested in receiving more education about lithium. The patients’ survey recruited 219 participants with 70.3% being current lithium users. Most patients (68%) found lithium helpful and 71% reported experiencing any kind of side effect. Most responders did not receive information about side effects or other benefits of lithium. Patients with higher scores on the LKT were more likely to have positive attitudes about lithium. LimitationsCross-sectional design with predominantly English-speaking participants from Brazil and North America. ConclusionsThere is a discrepancy between guidelines, clinician confidence and knowledge of lithium use and practice. A deeper understanding of how to monitor, prevent and manage long-term side effects and which patients are most likely to benefit from lithium may narrow the gap between knowledge and use.

Genomic conservation of crop wild relatives: A case study of citrus.

Conservation of crop wild relatives is critical for plant breeding and food security. The lack of clarity on the genetic factors that lead to endangered status or extinction create difficulties when attempting to develop concrete recommendations for conserving a citrus wild relative: the wild relatives of crops. Here, we evaluate the conservation of wild kumquat (Fortunella hindsii) using genomic, geographical, environmental, and phenotypic data, and forward simulations. Genome resequencing data from 73 accessions from the Fortunella genus were combined to investigate population structure, demography, inbreeding, introgression, and genetic load. Population structure was correlated with reproductive type (i.e., sexual and apomictic) and with a significant differentiation within the sexually reproducing population. The effective population size for one of the sexually reproducing subpopulations has recently declined to ~1,000, resulting in high levels of inbreeding. In particular, we found that 58% of the ecological niche overlapped between wild and cultivated populations and that there was extensive introgression into wild samples from cultivated populations. Interestingly, the introgression pattern and accumulation of genetic load may be influenced by the type of reproduction. In wild apomictic samples, the introgressed regions were primarily heterozygous, and genome-wide deleterious variants were hidden in the heterozygous state. In contrast, wild sexually reproducing samples carried a higher recessive deleterious burden. Furthermore, we also found that sexually reproducing samples were self-incompatible, which prevented the reduction of genetic diversity by selfing. Our population genomic analyses provide specific recommendations for distinct reproductive types and monitoring during conservation. This study highlights the genomic landscape of a wild relative of citrus and provides recommendations for the conservation of crop wild relatives.

1199-P: Timing of Postprandial Peak CGM Glucose in Gestational Diabetes

Background: Current guideline recommendations for management of gestational diabetes mellitus (GDM) recommend capillary testing of blood glucose levels fasting and one-two hours postprandial. Use of intermittently-scanned continuous glucose monitors (isCGM) during pregnancy in women with GDM has the potential to improve fetal outcomes, however there are limited recommendations for their use. Optimal timing of postprandial testing is unknown. Methods: Women with GDM diagnosed after 24 weeks gestation were recruited and randomized to adjunctive use of isCGM versus capillary testing with blinded CGM. In this subanalysis of 8 participants, timing of peak CGM glucose value is compared to recommended 1-hour postprandial capillary value. Food logs and/or meter data from the first two weeks of participation were used for analysis. Results: A total of 265 meals were analyzed. Gestational age at analysis was 29±1.2 weeks. One participant was treated with insulin. Three participants used blinded CGM; 5 used isCGM. Mean peak CGM glucose was 100±11 mg/dL. Mean time to peak was 96±14 minutes. Seventy-four percent of peak glucoses were after one hour. Conclusions: Current recommendations for glucose monitoring may need to be adapted to use of new technology with isCGM. Our data found that if a user only scanned at one hour postprandial, they could miss the peak glucose for the majority of meals. Repeat scanning or retrospective review of isCGM data may be required to determine the timing of a user’s postprandial peaks in relation to glycemic goals. Factors like the lag in CGM glucose compared to capillary testing and meal content should be considered with isCGM use. Disclosure G.O'malley: Research Support; Dexcom, Inc., Abbott Diabetes, Tandem Diabetes Care, Inc., Omnipod, Eli Lilly and Company. M.Kononenko: None. S.J.Ogyaadu: None. C.Levister: Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc., Abbott Diabetes. E.Ellis: None. D.Arumugam: None. L.Vieira: None. C.J.Levy: Advisory Panel; Dexcom, Inc., Research Support; Abbott Diabetes, Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Inc., T1D Exchange. Funding Abbott Diabetes Care

The multifaceted role of neuropsychology in pediatric solid organ transplant: preliminary guidelines and strategies for clinical practice

ABSTRACT The incidence of pediatric solid organ transplantation (SOT) has increased in recent decades due to medical and surgical advances as well as improvements in organ procurement. Survival rates for pediatric kidney, liver, and heart transplantation are above 85% but patients continue to experience complex healthcare needs over their lifetime. Long-term developmental and neuropsychological sequelae are becoming increasingly recognized in this population, although preliminary work is limited and deserves further attention. Neuropsychological weaknesses are often present prior to transplantation and may be related to underlying congenital conditions as well as downstream impact of the indicating organ dysfunction on the central nervous system. Neuropsychological difficulties pose risk for functional complications, including disruption to adaptive skill development, social-emotional functioning, quality of life, and transition to adulthood. The impact of cognitive dysfunction on health management activities (e.g., medication adherence, medical decision-making) is also an important consideration given these patients’ lifelong medical needs. The primary aim of this paper is to provide preliminary guidelines and clinical strategies for assessment of neuropsychological outcomes across SOT populations for pediatric neuropsychologists and the multidisciplinary medical team, including detailing unique and shared etiologies and risk factors for impairment across organ types, and functional implications. Recommendations for clinical neuropsychological monitoring as well as multidisciplinary collaboration within pediatric SOT teams are also provided.

The Population Development of the Invasive Round Goby Neogobius melanostomus in Latvian Waters of the Baltic Sea

The invasive round goby (Neogobius melanostomus) was established in the coastal waters of the Baltic Sea in the early 1990s. The first observation of the species in Latvian waters was in 2004. In the intervening period, the population grew, the species became of significance for local fisheries, and it likely impacted the local ecosystem in the Baltic Sea. In this study, we characterize the spatial–temporal population development of round goby in Latvian coastal waters using data from three different scientific and fisheries-independent surveys. We also include data from commercial fisheries landings to describe the fisheries targeting the species. Our results suggest an exponential increase in population numbers of round goby in Latvian waters, peaking in 2018, followed by a sharp decline. This observation is also supported by data from commercial fisheries landings. We suggest that intensive commercial fishing had a considerable impact on the rapid decline of the species, but that the decline was potentially amplified through a wider scale decline, as observed in many areas of the Baltic Sea. The results of this study contribute to the knowledge base on the species and how fisheries can aid in limiting the development of invasive fish populations. Based on the results of the study, we also provide recommendations for better future monitoring of the species in the coastal waters of the Baltic Sea.

Intrathecal opioids for the management of post-operative pain.

Intrathecal opioids are highly effective in the management of post-operative pain. The technique is simple with a very low risk of technical failure or complications, and it does not require additional training or expensive equipment such as ultrasound machines and, therefore, is widely practised around the world. The high-quality pain relief is not associated with sensory, motor or autonomic deficits. This study focuses on intrathecal morphine (ITM) which is the only US Food and Drug Administration-approved opioid for intrathecal administration and remains the most commonly used as well as extensively studied. The use of ITM is associated with prolonged analgesia lasting 20-48h after a variety of surgical procedures. ITM has a well-established role in thoracic, abdominal, spinal, urological and orthopaedic surgeries. It is considered the 'gold standard' analgesia technique for caesarean delivery which is generally performed under spinal anaesthesia. As the role of epidural technique in post-operative pain management continues to decrease, ITM has emerged as the neuraxial technique of choice for pain management after a major surgery as a component of multimodal analgesia in Enhanced Recovery After Surgery (ERAS) protocols. ITM is recommended by many scientific groups and societies such as ERAS, PROSPECT, the National Institute for Health and Care Excellence and the Society of Obstetric Anesthesiology and Perinatology. The doses of ITM have decreased successively; today they are a fraction of those used in the early 1980s. With these dose reductions, the risks have decreased; current evidence shows that the risk of the much-feared respiratory depression with low-dose ITM (up to 150 mcg) is no greater than that with systemic opioids used in routine clinical practice. Patients receiving low-dose ITM can be nursed in regular surgical wards. The monitoring recommendations from societies such as the European Society of Regional Anaesthesia and Pain Therapy (ESRA), the American Society of Regional Anesthesia and Pain Medicine and the American Society of Anesthesiologists need to be updated so that the requirements for extended or continuous monitoring at postoperative care units (PACUs), step-down units, high-dependency units, and intensive care units can be eliminated, thereby reducing additional costs and inconvenience and making this simple, versatile and highly effective analgesia technique available to a wider patient population in resource-limited settings.

Management of Muscle Relaxation With Rocuronium and Reversal With Neostigmine or Sugammadex Guided by Quantitative Neuromuscular Monitoring.

The optimal pharmacological reversal strategy for neuromuscular blockade remains undefined even in the setting of strong recommendations for quantitative neuromuscular monitoring by several national and international anesthesiology societies. We evaluated a protocol for managing rocuronium blockade and reversal, using quantitative monitoring to guide choice of reversal agent and to confirm full reversal before extubation. We conducted a prospective cohort study and enrolled 200 patients scheduled for elective surgery involving the intraoperative use of rocuronium. Providers were asked to adhere to a protocol that was similar to local practice recommendations for neuromusculalr block reversal that had been used for >2 years; the protocol added quantitative monitoring that had not previously been routinely used at our institution. In this study, providers used electromyography-based quantitative monitoring. Pharmacological reversal was accomplished with neostigmine if the train-of-four (TOF) ratio was 0.40 to 0.89 and with sugammadex for deeper levels of blockade. The primary end point was the incidence of postoperative residual neuromuscular blockade (PRNB), defined as TOF ratio <0.9 at time of extubation. We further evaluated the difference in pharmacy costs had all patients been treated with sugammadex. A total of 189 patients completed the study: 66 patients (35%) were reversed with neostigmine, 90 patients (48%) with sugammadex, and 33 (17%) patients recovered spontaneously without pharmacological reversal. The overall incidence of residual paralysis was 0% (95% CI, 0-1.9). The total acquisition cost for all reversal drugs was United States dollar (USD) 11,358 (USD 60 per patient) while the cost would have been USD 19,312 (USD 103 per patient, 70% higher) if sugammadex had been used in all patients. A protocol that includes quantitative monitoring to guide reversal with neostigmine or sugammadex and to confirm TOF ratio ≥0.9 before extubation resulted in the complete prevention of PRNB. With current pricing of drugs, the selective use of sugammadex reduced the total cost of reversal drugs compared to the projected cost associated with routine use of sugammadex for all patients.

Challenges and lessons learnt from Northern Territory (NT) Orphan Well project

The Orphan Well project evolved from recommendations in the Final Report of the NT Hydraulic Fracturing Inquiry (HFI). The purpose was to assess wells that were drilled under petroleum permit or licence, and which had subsequently been surrendered by the titleholder and are now the responsibility of the NT Government. The project’s objective was to confirm the current status of these wells and to put forward recommendations for remedial works and/or monitoring for wells assessed to have an integrity risk. The assessment primarily focusses on the risk of fugitive methane gas. Two petroleum engineers were employed to undertake the project of assessing 113 orphan wells scattered over 1.4 million km2 of the NT. As it is a requirement to rehabilitate the land after petroleum activities have ceased, access to orphan wells is often not maintained; therefore, logistical consideration was undertaken. The project involved an initial desktop study of well history (construction) followed by a field site inspection. The drilling of these wells date back to the 1960s. These older wells can often have less detail in the well records including survey location, and being pre-GPS, may include location errors of several kilometres. Remote helicopter travel was used to undertake fieldwork and to locate these wells. The site inspections commenced in February 2022 and as at 31 December 2022 on ground field inspections were delivered to 96 wellsites. This paper provides insight as to how the Orphan Well team developed its processes in both desktop study and site investigations.

A comprehensive early warning system for karst water sources contamination risk, case study of the Unica springs, SW Slovenia

Water suppliers should provide safe drinking water following preventive measures. This is especially important for karst water sources, as they are among the most vulnerable. Recently, there has been a strong focus on the early warning system, which mainly involves monitoring proxy parameters, but does not consider drainage area conditions and other monitoring recommendations. Here, we present an innovative strategy for assessing contamination risk of karst water sources that covers spatio-temporal dimensions and can be integrated into management practices. It is based on event-based monitoring and risk mapping and has been tested in a well-known study area. The holistic early warning system provides accurate spatial hazard and risk assessment and operational monitoring guidelines, including locations, indicator parameters, and temporal resolution and duration. In the study area, the high contamination risk, representing 0.5 % of the area, was spatially delineated. The highest probability of source contamination occurs during recharge events when proxy parameters such as bacteria, ATP, Cl, and Ca/Mg ratio should be monitored in addition to continuous monitoring of turbidity, EC, and T. Monitoring of sinking streams should serve as a preventive measure, since water transfer from ponors to springs has been shown to take about one day, and poor quality water is present for at least another day. Therefore, intensive monitoring should be conducted at intervals of a few hours for at least a week. Although hydrologic systems vary, the proposed strategy is particularly useful in systems where water flows rapidly and where remediation is not feasible.

Variable Clinical Presentation in Individuals with Truncating Variants in DDX41

Background and AimsDefects in DDX41 have previously been associated with increased risk of myeloid neoplasms, lymphoid neoplasms, cytopenia, and red blood cell macrocytosis. DDX41-related phenotypes have a variable age of onset typically in the 60 s. A previous study analyzed a cohort of 1,385 individuals with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), identifying 33 individuals with a pathogenic variant in DDX41, 9 of whom had a familial history of MDS/AML. In our cohort of 6,103 participants with diverse clinical manifestations, we identified 7 individuals with truncating variants in DDX41. We sought to characterize age-related penetrance and the phenotypic spectrum of individuals with DDX41 truncating variants. MethodsWe performed exome or genome sequencing on DNA extracted from blood, saliva, fibroblasts, or EBV-transformed cell lines in individuals referred to the Centralized Sequencing Program at the NIH for immune-related, neurological, psychiatric, and other clinical indications. ResultsWe identified 7 subjects with truncating variants in DDX41, including 3 different frameshift variants in 5 subjects and 2 different nonsense variants in the other 2 subjects. The average age of subjects was 37 years old, ranging from 5 to 76 years old at time of enrollment. There were 3 males and 4 females. Family history of DDX41-related phenotypes was not reported in the families; furthermore, there were no familial cases, thought segregation data was incomplete. Clinical features were highly variable, ranging from a healthy volunteer to an individual with JAK2 p. Val617Phe-associated eosinophilic myeloid neoplasm. Previously associated DDX41-related phenotypes were not observed in the 7 subjects even include those above 60. ConclusionsHere, we report 7 subjects with truncating variants in DDX41. These individuals have variable immune phenotypes and further studies are necessary to delineate whether they are attributed to DDX41 truncating variants. Detection of DDX41-defects in younger individuals prior to symptom onset poses genetic counseling challenges given the long latency period and minimal evidence-based management guidelines at present. Nonetheless, current expert-based clinical recommendations for management and monitoring may provide clinical benefit upon further study. Additional studies of clinical and sub-clinical features in expanded cohorts are warranted to further delineate DDX41-related disease risk.

The importance of monitoring cerebral oxygenation in non brain injured patients.

Over the past few years, the use of non-invasive neuromonitoring in non-brain injured patients has increased, as a result of the recognition that many of these patients are at risk of brain injury in a wide number of clinical scenarios and therefore may benefit from its application which allows interventions to prevent injury and improve outcome. Among these, are post cardiac arrest syndrome, sepsis, liver failure, acute respiratory failure, and the perioperative settings where in the absence of a primary brain injury, certain groups of patients have high risk of neurological complications. While there are many neuromonitoring modalities utilized in brain injured patients, the majority of those are either invasive such as intracranial pressure monitoring, require special skill such as transcranial Doppler ultrasonography, or intermittent such as pupillometry and therefore unable to provide continuous monitoring. Cerebral oximetry using Near infrared Spectroscopy, is a simple non invasive continuous measure of cerebral oxygenation that has been shown to be useful in preventing cerebral hypoxemia both within the intensive care unit and the perioperative settings. At present, current recommendations for standard monitoring during anesthesia or in the general intensive care concentrate mainly on hemodynamic and respiratory monitoring without specific indications regarding the brain, and in particular, brain oximetry. The aim of this manuscript is to provide an up-to-date overview of the pathophysiology and applications of cerebral oxygenation in non brain injured patients as part of non-invasive multimodal neuromonitoring in the early identification and treatment of neurological complications in this population.

A review of gray whales (Eschrichtius robustus) on their wintering grounds in Mexican waters

The Eastern North Pacific gray whale (Eschrichtius robustus) is one population of large cetacean that has recovered from depletion resulting from commercial harvest in the mid- to late-1800s. It is believed that this population may be approaching, or possibly exceeding its carrying capacity as suggested by recent increases in mortality of all age and sex classes. Research on the breeding biology and phenology of gray whales that spend the winter in the coastal waters and lagoons of Baja California, Mexico has been conducted for many years. These studies contribute valuable information on the reproductive biology of this species, and the importance of their coastal lagoon habitats to their reproductive success. This paper reviews and summarises historical exploitation, conservation measures, the findings of research conducted on gray whales in their winter breeding range, potential natural and anthropogenic threats to this population, and makes recommendations for future research and monitoring. This review concentrates on the findings of research conducted since the mid-1970s.