Polyphenic risk score shows robust predictive ability for long-term future suicidality.

Suicides are preventable tragedies, if risk factors are tracked and mitigated. We had previously developed a new quantitative suicidality risk assessment instrument (Convergent Functional Information for Suicidality, CFI-S), which is in essence a simple polyphenic risk score, and deployed it in a busy urban hospital Emergency Department, in a naturalistic cohort of consecutive patients. We report a four years follow-up of that population (n = 482). Overall, the single administration of the CFI-S was significantly predictive of suicidality over the ensuing 4 years (occurrence- ROC AUC 80%, severity- Pearson correlation 0.44, imminence-Cox regression Hazard Ratio 1.33). The best predictive single phenes (phenotypic items) were feeling useless (not needed), a past history of suicidality, and social isolation. We next used machine learning approaches to enhance the predictive ability of CFI-S. We divided the population into a discovery cohort (n = 255) and testing cohort (n = 227), and developed a deep neural network algorithm that showed increased accuracy for predicting risk of future suicidality (increasing the ROC AUC from 80 to 90%), as well as a similarity network classifier for visualizing patient's risk. We propose that the widespread use of CFI-S for screening purposes, with or without machine learning enhancements, can boost suicidality prevention efforts. This study also identified as top risk factors for suicidality addressable social determinants. Supplementary Information: The online version contains supplementary material available at 10.1007/s44192-022-00016-z.

The BeSMART (Best Supportive Management for Adults Referred with Tonsillopharyngitis) multicentre observational study.

Introduction Tonsillopharyngitis is the most common ear, nose and throat emergency admission, with 80,000 episodes recorded in England in 2015-2016. Despite this, there is a paucity of evidence addressing the supportive management of tonsillopharyngitis in inpatients. The aim of this retrospective multicentre observational study was to consider the Best Supportive Management for Adults Referred with Tonsillopharyngitis (BeSMART) in the inpatient setting, and to establish any associations between practice and outcomes. Methods Seven hospitals in North West England and North East Scotland participated in the study. Overall, 236 adult patients admitted with tonsillopharyngitis were included. The main outcome measures were interval to return to soft diet, length of stay (LOS), pain scores and readmissions. Results Women were more likely to seek professional help before presenting to secondary care (p=0.04). Patients admitted at the weekend were more likely to have a shorter LOS (p=0.03). There was no relationship between day of admission and seniority or specialty of the doctor initially seen. Prescription of corticosteroid, analgesia and a higher initial intravenous fluid infusion rate were not related to a shorter LOS. Conclusions This study is the first to yield valuable insights into the inpatient management of tonsillopharyngitis. This work represents part of an ongoing project to establish the evidence for common medical interventions for sore throat. Patient and professional surveys as well as a prospective interventional study are planned for the future.

Depo medroxyprogesterone acetate (DMPA) and combined oral contraceptives and cervical carcinoma in-situ in women aged 50 years and under

Most low-resource settings depend on hormonal contraceptives for their family planning programmes and cervical cancer occurs in higher frequency in these populations. To determine whether hormonal contraception use increases cervical carcinoma in-situ (CIS) risk, a case-control study was conducted in the Kingston and St Andrew Corporate area of Jamaica, using 119 cases from the Jamaica Tumour Registry and 304 population controls matched on year of Papanicolaou (Pap) smear and clinic where Pap smear was obtained. While CIS cases were more likely to have 'ever used' combined oral contraceptives (COC) (OR = 1.4, 95 CI: 0.8, 2.5), depo-medroxyprogesterone acetate (DMPA) use was similar. Compared to women who never used hormonal contraceptives, the risk of CIS was elevated in: women who had used COCs five years or more (OR = 2.1, 95 CI: 1.0, 4.6), women who first used COC for less than 10 years prior to the interview (OR = 1.8, 95 CI: 0.9, 3.7) and women who were 18 to 24 years old when they first used COCs (OR = 1.8, 95 CI: 0.9, 3.4). Similarly, compared to women who never used DMPA, the risk of CIS was elevated in: women using DMPA five years or more (OR = 1.9, 95 CI: 0.7, 4.8), women reporting use within a year prior to interview (OR = 2.8, 95 CI: 0.7, 10.7) and women who initiated use of DMPA when they were 20 and 24 years old (OR = 1.4, 95 CI: 0.7, 3.1). These results suggest that if hormonal contraceptive use confers any risk of CIS, it is confined to long-term users. Increased risk in some groups, however, warrant further study

Depo medroxyprogesterone acetate (DMPA) and combined oral contraceptives and cervical carcinoma in-situ in women aged 50 years and under.

Most low-resource settings depend on hormonal contraceptives for their family planning programmes and cervical cancer occurs in higher frequency in these populations. To determine whether hormonal contraception use increases cervical carcinoma in-situ (CIS) risk, a case-control study was conducted in the Kingston and St Andrew Corporate area of Jamaica, using 119 cases from the Jamaica Tumour Registry and 304 population controls matched on year of Papanicolaou (Pap) smear and clinic where Pap smear was obtained. While CIS cases were more likely to have 'ever used' combined oral contraceptives (COC) (OR = 1.4, 95% CI: 0.8, 2.5), depo-medroxyprogesterone acetate (DMPA) use was similar. Compared to women who never used hormonal contraceptives, the risk of CIS was elevated in: women who had used COCs five years or more (OR = 2.1, 95% CI: 1.0, 4.6), women who first used COC for less than 10 years prior to the interview (OR = 1.8, 95% CI: 0.9, 3.7) and women who were 18 to 24 years old when they first used COCs (OR = 1.8, 95% CI: 0.9, 3.4). Similarly, compared to women who never used DMPA, the risk of CIS was elevated in: women using DMPA five years or more (OR = 1.9, 95% CI: 0.7, 4.8), women reporting use within a year prior to interview (OR = 2.8, 95% CI: 0.7, 10.7) and women who initiated use of DMPA when they were 20 and 24 years old (OR = 1.4, 95% CI: 0.7, 3.1). These results suggest that if hormonal contraceptive use confers any risk of CIS, it is confined to long-term users. Increased risk in some groups, however, warrant further study.

Antibody neutralization of vascular endothelial growth factor inhibits wound granulation tissue formation.

OBJECTIVE: The goal of this work was to test the functional role of vascular endothelial growth factor (VEGF) in promoting the vigorous granulation tissue formation, wound fluid accumulation, and angiogenic responses characteristic of this wound model. BACKGROUND: Formation of vessel-rich granulation tissue is central to wound repair and is thought to be regulated by locally liberated angiogenic factors. Despite the clinical importance of granulation tissue formation in the early stage of wound healing, surprisingly little is known about the molecular identity of signals leading to granulation tissue invasion of a wound space. Methods. A ventral hernia, surgically created in the abdominal wall of 15 swine, was repaired using silicone sheeting and skin closure. An osmotic minipump, inserted in a remote subcutaneous pocket, delivered saline (n = 5), an irrelevant control antibody (n = 5), or neutralizing anti-VEGF antibody (n = 5) into the wound environment. Serial ultrasonography on Days 2, 4, 7, 9, 11, and 14 was used to determine the dimensions of the subcutaneous granulation tissue and wound fluid compartment. VEGF and transforming growth factor beta1 (TGF-beta1) levels in serial wound fluid samples were quantitated by ELISA. On Day 14, animals were sacrificed and the abdominal wall was harvested for histologic, biochemical, and molecular analyses. RESULTS: In animals receiving saline or an irrelevant antibody, a nearly linear 4-fold increase in granulation tissue thickness and 7-fold increase in wound fluid volume were measured over the 14-day study interval. In contrast, in animals receiving anti-VEGF neutralizing antibody, Day 14 granulation tissue thickness and wound fluid volume measurements were essentially unchanged from Day 2 values. Moreover, in the anti-VEGF animals, ultrasonography was unable to resolve the "angiogenic zone" typical of both controls, and correspondingly, wound vessel count and vascular surface area estimates derived from image analysis of histological sections were 3-fold lower in the anti-VEGF animals compared with the saline and antibody controls. Finally, VEGF levels in wound fluid detectable by ELISA analysis were strikingly (10-fold) reduced in anti-VEGF animals on Postsurgery Days 7-14. In contrast, TGF-beta1 levels were unaffected by the anti-VEGF treatment. CONCLUSION: Functional VEGF is a key mediator in wound angiogenesis, fluid accumulation, and granulation tissue formation.

Retrospective analysis of the effect of crossing vessels on successful retrograde endopyelotomy outcomes using spiral computerized tomography angiography.

PURPOSE: Using spiral computerized tomography (CT) angiography, we sought to evaluate the incidence of a crossing vessel in a group of adults with primary ureteropelvic junction obstruction who had previously undergone successful retrograde endopyelotomy. MATERIALS AND METHODS: A total of 16 patients who had undergone successful Acucise balloon incision endopyelotomy for ureteropelvic junction obstruction, all with followup greater than 2 years, underwent a spiral CT angiogram with intravenous contrast material to identify those with a crossing vessel. Contrast enhanced CT was performed with dual phase technique on a Somatom-Plus-S CT scanner using prototype software. After 180-degree linear interpolation of the projection data, transaxial images of the affected kidney were reconstructed. In addition, at the time of the study all patients completed analog followup pain scales and quality of life assessment questionnaires. RESULTS: Among the 16 patients 6 (38%) had anterior or posterior crossing vessels based on spiral CT angiography. No patient had both types. By analog pain scale patients had 80% mean improvement in pain (range 63 to 100). CONCLUSIONS: In our series nearly 40% of patients with anterior or posterior crossing vessels had a long-term (greater than 2 years) successful outcome with retrograde endopyelotomy. Endopyelotomy continues to be our initial mode of therapy among adults with primary ureteropelvic junction obstruction. In our opinion the adverse influence of the crossing vessel is not sufficient to justify the added expense of preoperative angiography, spinal CT or endoluminal ultrasound.

The effects of habitat fragmentation on the genetic structure of small mammal populations.

We present five case studies highlighting the effects of habitat fragmentation on the genetic structure of small mammal populations. The studies reflect different spatial scales and components of genetic variation. In marginal and central populations of Sigmodon hispidus we found less allozymic variation within the marginal population, whereas patterns of morphological variability were the converse. In the rice rat (Oryzomys spp.), nucleotide diversity in mtDNA was similar in an island population in the Florida Keys to mainland populations in the Everglades. This observation contrasts with insular vole populations (Microtus spp.), where isolation on islands results in genetic structuring. Temporal changes in abundance in mainland populations had no effects on genetic differentiation (FST values) because subpopulations did not experience bottlenecks. In an experimentally fragmented landscape, fragmentation influenced demographic processes but not genetic structure. We conclude that (1) with extreme fragmentation, small mammal populations become depauperate of genetic variation and differentiate genetically; (2) different components of genetic variation lead to different genetic structuring; (3) spatial and temporal scales should both be considered when examining genetic structure of populations; (4) demographic and ecological processes are more likely influenced by fragmentation than genetic structure; and (5) there is an interaction between demographic processes and genetic structure.

Using standard situations to measure attention span and persistence in toddler-aged children: some cautions.

This study was conducted with 38 children, 23-25 months old, to evaluate the use of standard situations to measure individuals differences in attention span and persistence. A vigilance task was used to measure attention span and three problem-solving tasks to measure persistence. Three delay tasks were used to measure inhibitory control, a personality trait hypothesized to be a correlate of attention span and persistence. Results showed (a) some consistency in performance within the persistence tasks but not across these tasks, (b) poor consistency in performance within the vigilance task, and (c) good consistency in performance across the delay tasks. No significant interrelations were found among the persistence, attention span, and delay measures. Developmental status, as measured by maternal report, was not related to any of the measures.

High Performance Liquid Chromatographic Analysis of Enantiomeric Composition of Abuse Drugs.

Numerous commonly abused drugs exist in two enantiomeric forms. Identifying the exact enantiomeric form is essential when only one of these two enantiomers is a controlled substance. Enantiomeric composition data may also help the investigation of clandestine laboratory activities. Although generally not as convenient as gas chromatographic methods, liquid chromatographic methods (LC) allow for the selection of larger and hopefully more effective derivatizing groups and the use of an "active" mobile phase. LC-based enantiomeric resolution approaches include derivatization with chiral agents, incorporation of chiral additives in the mobile phase, and the use of chiral stationary phases. Various applications of these approaches are reviewed.Unique detection procedures that were adopted in enantiomeric analysis are also reviewed.

Dynamic incremental CT: effect of volume and concentration of contrast material and patient weight on hepatic enhancement.

PURPOSE: To develop an individualized approach to the intravenous administration of contrast material for hepatic computed tomography (CT). MATERIALS AND METHODS: Two hundred patients were randomized into eight protocols. Each group received different volumes and concentrations of contrast material. For each protocol, maximum hepatic enhancement (MHE) was calculated, with an adjustment for iodine dose and patient weight. The contrast enhancement index (CEI) and optimum scanning interval were calculated for hepatic enhancement thresholds of 10-60 HU. RESULTS: The MHE calculated as a function of patient weight was 96 HU +/- 19 per gram of iodine per kilogram of body weight. CEIs obtained with a contrast material concentration of 240 mg of iodine per milliliter were inferior to those obtained with a concentration of 320 or 350 mg I/mL. At low enhancement thresholds, the volume of contrast material had a more important effect than the concentration on CEI and optimum scanning interval; at high thresholds, concentration had a more important effect. CONCLUSION: For a patient of known weight, one can calculate the iodine dose needed to provide a desired level of hepatic enhancement. Use of a contrast material with a concentration of 240 mg L/mL is not recommended for dynamic incremental hepatic CT, except in small patients (eg, those weighing less than 73 kg).

Diverse and contrasting effects of habitat fragmentation.

Different components of an ecosystem can respond in very different ways to habitat fragmentation. An archipelago of patches, representing different levels of fragmentation, was arrayed within a successional field and studied over a period of 6 years. Ecosystem processes (soil mineralization and plant succession) did not vary with the degree of subdivision, nor did most measures of plant and animal community diversity. However, fragmentation affected vertebrate population dynamics and distributional patterns as well as the population persistence of clonal plant species. The results highlight the dangers of relying on broad community measures in lieu of detailed population analyses in studies of fragmented habitats.

Effect of experimental hemorrhagic shock on hepatic drug elimination.

OBJECTIVE: Exogenous substrates were used to measure hepatic function for the purposes of determining organ dysfunction and to evaluate the effect of experimental hemorrhagic shock with resuscitation on hepatic drug elimination. DESIGN: Prospective, controlled, non-randomized crossover trial. INTERVENTIONS: Eleven chronically instrumented immature swine were studied using a fixed-volume hemorrhage model (45 mL/kg blood removal over 15 mins) followed by resuscitation with lactated Ringer's solution at three times the volume of shed blood. One week before and immediately after hemorrhage and resuscitation, hepatic function markers (indocyanine green and antipyrine) were simultaneously administered intravenously. MEASUREMENTS: Physiologic data and blood samples were collected over 12 hrs after drug administration. Drug clearances, volumes of distribution, and half-lives were determined. MAIN RESULTS: For indocyanine green, there was no substantial change in pharmacokinetics from preshock to postshock, suggesting minimal change in hepatic blood flow. For antipyrine, clearance was decreased by 30% after shock and resuscitation (p = .05), suggesting that oxidative metabolism was acutely impaired. CONCLUSIONS: The information indicates that hepatic oxidative drug metabolism may be impaired early after hemorrhagic shock and that dosages of drugs in this class should be carefully examined when administered to patients who have sustained injury with hemorrhagic shock.

Genetic changes in fluctuating vole populations: selective vs. nonselective forces.

The Lewontin-Krakauer test for selective neutrality of polymorphisms was applied to temporal variation in gene frequency at five electrophoretic loci in each of four fluctuating vole populations over a three-year period. The results indicate that changes in gene frequencies were primarily due to nonselective forces.

Population cycles in small rodents.

We conclude that population fluctuations in Microtus in southern Indiana are produced by a syndrome of changes in birth and death rates similar to that found in other species of voles and lemmings. The mechanisms which cause the changes in birth and death rates are demolished by fencing the population so that no dispersal can occur. Dispersal thus seems critical for population regulation in Microtus. Because most dispersal occurs during the increase phase of the population cycle and there is little dispersal during the decline phase, dispersal is not directly related to population density. Hence the quality of dispersing animals must be important, and we have found one case of increased dispersal tendency by one genotype. The failure of population regulation of Microtus in enclosed areas requires an explanation by any hypothesis attempting to explain population cycles in small rodents. It might be suggested that the fence changed the predation pressure on the enclosed populations. However, the fence was only 2 feet (0.6 meter) high and did not stop the entrance of foxes, weasels, shrews, or avian predators. A striking feature was that the habitat in the enclosures quickly recovered from complete devastation by the start of the spring growing season. Obviously the habitat and food quality were sufficient to support Microtus populations of abnormally high densities, and recovery of the habitat was sufficiently quick that the introduction of new animals to these enclosed areas resulted in another population explosion. Finally, hypotheses of population regulation by social stress must account for the finding that Microtus can exist at densities several times greater than normal without "stress" taking an obvious toll. We hypothesize that the prevention of dispersal changes the quality of the populations in the enclosures in comparison to those outside the fence. Voles forced to remain in an overcrowded fenced population do not suffer high mortality rates and continue to reproduce at abnormally high densities until starvation overtakes them. The initial behavioral interactions associated with crowding do not seem sufficient to cause voles to die in situ. What happens to animals during the population decline? Our studies have not answered this question. The animals did not appear to disperse, but it is possible that the method we used to measure dispersal (movement into a vacant habitat) missed a large segment of dispersing voles which did not remain in the vacant area but kept on moving. Perhaps the dispersal during the increase phase of the population cycle is a colonization type of dispersal, and the animals taking part in it are likely to stay in a new habitat, while during the population decline dispersal is a pathological response to high density, and the animals are not attracted to settling even in a vacant habitat. The alternative to this suggestion is that animals are dying in situ during the decline because of physiological or genetically determined behavioral stress. Thus the fencing of a population prevents the change in rates of survival and reproduction, from high rates in the increase phase to low rates in the decline phase, and the fenced populations resemble "mouse plagues." A possible explanation is that the differential dispersal of animals during the phase of increase causes the quality of the voles remaining at peak densities in wild populations to be different from the quality of voles at much higher densities in enclosures. Increased sensitivity to density in Microtus could cause the decline of wild populations at densities lower than those reached by fenced populations in which selection through dispersal has been prevented. Fencing might also alter the social interactions among Microtus in other ways that are not understood. The analysis of colonizing species by MacArthur and Wilson (27) can be applied to our studies of dispersal in populations of Microtus. Groups of organisms with good dispersal and colonizing ability are called r strategists because they have high reproductive potential and are able to exploit a new environment rapidly. Dispersing voles seem to be r strategists. Young females in breeding condition were over-represented in dispersing female Microtus (17). The Tf(C)/Tf(E) females, which were more common among dispersers during the phase of population increase (Fig. 6), also have a slight reproductive advantage over the other Tf genotypes (19). Thus in Microtus populations the animals with the highest reproductive potential, the r strategists, are dispersing. The segment of the population which remains behind after the selection-via-dispersal are those individuals which are less influenced by increasing population densities. These are the individuals which maximize use of the habitat, the K strategists in MacArthur and Wilson's terminology, or voles selected for spacing behavior. Thus we can describe population cycles in Microtus in the same theoretical framework as colonizing species on islands. Our work on Microtus is consistent with the hypothesis of genetic and behavioral effects proposed by Chitty (6) (Fig. 7) in that it shows both behavioral differences in males during the phases of population fluctuation and periods of strong genetic selection. The greatest gaps in our knowledge are in the area of genetic-behavioral interactions which are most difficult to measure. We have no information on the heritability of aggressive behavior in voles. The pathways by which behavioral events are translated into physiological changes which affect reproduction and growth have been carefully analyzed by Christian and his associates (28) for rodents in laboratory situations, but the application of these findings to the complex field events described above remains to be done. Several experiments are suggested by our work. First, other populations of other rodent species should increase to abnormal densities if enclosed in a large fenced area (29). We need to find situations in which this prediction is not fulfilled. Island populations may be an important source of material for such an experiment (30). Second, if one-way exit doors were provided from a fenced area, normal population regulation through dispersal should occur. This experiment would provide another method by which dispersers could be identified. Third, if dispersal were prevented after a population reached peak densities, a normal decline phase should occur. This prediction is based on the assumption that dispersal during the increase phase is sufficient to ensure the decline phase 1 or 2 years later. All these experiments are concerned with the dispersal factor, and our work on Microtus can be summarized by the admonition: study dispersal.