Search

Assessing and managing pain while evaluating risks associated with substance use and substance use disorders continues to be a challenge faced by health care clinicians. The American Society for Pain Management Nursing and the International Nurses Society on Addictions uphold the principle that all persons with co-occurring pain and substance use or substance use disorders have the right to be treated with dignity and respect, and receive evidence-based, high quality assessment, and management for both conditions. The American Society for Pain Management Nursing and International Nurses Society on Addictions have updated their 2012 position statement on this topic supporting an integrated, holistic, multidimensional approach, which includes nonopioid and nonpharmacological modalities. Opioid use disorder is used as an exemplar for substance use disorders and clinical recommendations are included with expanded attention to risk assessment and mitigation with interventions targeted to minimize the risk for relapse or escalation of substance use. Opioids should not be excluded for anyone when indicated for pain management. A team-based approach is critical, promotes the active involvement of the person with pain and their support systems, and includes pain and addiction specialists whenever possible. Health care systems should establish policies and procedures that facilitate and support the principles and recommendations put forth in this article.

The American Society for Pain Management Nursing and the International Nurses Society on Addictions hold the position that persons with co-occurring pain and substance use disorder have the right to be treated with dignity and respect, and receive evidence-based, high-quality assessment and management for both conditions using an integrated, holistic, multidimensional approach. Non-opioid and nonpharmacological approaches to pain management are recommended. Opioids should not be withheld from anyone if necessary to treat pain, and a team-based approach, including pain and addiction specialists, should be utilized when possible. Pain management should include interventions aimed at minimizing the risk for relapse or escalation of problematic substance use, and actively involve the person and their support persons in the plan of care. Institutions should establish policies and procedures that support this position statement.

Background\ud Anterior cruciate ligament (ACL) reconstruction has a detrimental impact on athletic performance. Despite rehabilitation guidelines and criterion-based progressions to ensure safe restoration of fundamental physical capacities and maladaptive movement strategies, residual deficits in maximal strength, rate of force development (RFD), power and reactive strength are commonly reported. These combined with associated compensatory inter and intra-limb strategies increase the risk of re-injury.\ud \ud Objective\ud The aim of this article is to examine the relationships between fundamental physical capacities and biomechanical variables during dynamic movement tasks.\ud \ud Design\ud Narrative review\ud \ud Results\ud The available data suggests that quadriceps strength and rate of torque development, explain a moderate portion of the variance in aberrant kinetic and kinematic strategies commonly detected in ACL reconstructed cohorts at who are during the later stages of rehabilitation and RTS\ud \ud Conclusion\ud The available data suggests that quadriceps strength and rate of torque development, explain a moderate portion of the variance in aberrant kinetic and kinematic strategies commonly detected in ACL reconstructed cohorts at who are in the later stages of rehabilitation and RTS

Genomic assemblies of the unicellular green alga Chlamydomonas reinhardtii have provided important resources for researchers. However, assembly errors, large gaps, and unplaced scaffolds as well as strain-specific variants currently impede many types of analysis. By combining PacBio HiFi and Oxford Nanopore long-read technologies, we generated a de novo genome assembly for strain CC-5816, derived from crosses of strains CC-125 and CC-124. Multiple methods of evaluating genome completeness and base-pair error rate suggest that the final telomere-to-telomere assembly is highly accurate. The CC-5816 assembly enabled previously difficult analyses that include characterization of the 17 centromeres, rDNA arrays on three chromosomes, and 56 insertions of organellar DNA into the nuclear genome. Using Nanopore sequencing, we identified sites of cytosine (CpG) methylation, which are enriched at centromeres. We analyzed CRISPR-Cas9 insertional mutants in the PF23 gene. Two of the three alleles produced progeny that displayed patterns of meiotic inviability that suggested the presence of a chromosomal aberration. Mapping Nanopore reads from pf23-2 and pf23-3 onto the CC-5816 genome showed that these two strains each carry a translocation that was initiated at the PF23 gene locus on chromosome 11 and joined with chromosomes 5 or 3, respectively. The translocations were verified by demonstrating linkage between loci on the two translocated chromosomes in meiotic progeny. The three pf23 alleles display the expected short-cilia phenotype, and immunoblotting showed that pf23-2 lacks the PF23 protein. Our CC-5816 genome assembly will undoubtedly provide an important tool for the Chlamydomonas research community.

Background\ud Residual deficits in athletic performance are common despite rehabilitation guidelines following anterior cruciate ligament reconstruction including criterion-based progressions to protect healing structures, ensure safe restoration of fundamental physical capacities, and guide appropriate return to sports activities. A synthesis of the available literature is warranted to examine the physical readiness to re-perform of athletic populations in the later stages of rehabilitation in comparison to healthy controls.\ud \ud Objectives\ud To determine the level of strength, power, rate of force development, and reactive strength in adult males who are more than six months following anterior cruciate ligament reconstruction.\ud \ud Methods\ud A systematic review of the literature was undertaken using the Medline, CINAHL and SPORTDiscus databases and the PRISMA (Preferred Reporting Items for Systematic\ud Reviews and Meta-Analyses) guidelines. Studies including males only and assessed strength, power, rate of force development and reactive strength comparing performance to healthy controls were included. A meta-analysis was also performed to compute standardized mean differences (SMD ± 95% confidence intervals), calculated using Hedge’s g, and examine the effect of ACLR on these fundamental physical capacities.\ud \ud Results\ud 2023 articles were identified, of which 14 articles with similar level of evidence and methodological quality met the inclusion criteria. The most commonly investigated and impaired physical capacity was quadriceps (g= -0.89, 95% CI [-1.33,-0.44]) and hamstring strength (g= -0.44, 95% CI [-0.78,-0.10]). Only one study investigated rate of force development and none measuring reactive strength met our eligibility criteria.\ud \ud Conclusions\ud Pooled data showed moderate evidence indicating large and small negative deficits on knee peak extension and flexion, respectively, in male adults at more than 6 months post anteriorcruciate ligament reconstruction. The magnitude of these differences are influenced by graft type and can be mitigated by targeted rehabilitation programs. Insufficient evidence is available in male adults following anterior cruciate ligament reconstruction to examine rate of force development and reactive strength.

Background Variants disruptive to CHD8 (which codes for the protein CHD8 [chromodomain-helicase-DNA-binding protein 8]) are among the most common mutations revealed by exome sequencing in autism spectrum disorder (ASD). Recent work has indicated that CHD8 plays a role in the regulation of other ASD-risk genes. However, it is unclear whether a possible shared genetic ontology extends to the phenotype. Methods This study (N = 143; 42.7% female participants) investigated clinical and behavioral features of individuals ascertained for the presence of a known disruptive ASD-risk mutation that is 1) CHD8 (CHD8 group) (n = 15), 2) a gene targeted by CHD8 (target group) (n = 22), or 3) a gene without confirmed evidence of being targeted by CHD8 (other gene group) (n = 106). Results Results indicated shared features between the CHD8 and target groups that included less severe adaptive deficits in communication skills, similar functional language, more social motivation challenges in those with ASD, larger head circumference, higher weight, and lower seizure prevalence relative to the other gene group. Conclusions These similarities suggest broader genetic ontology accounts for aspects of phenotypic heterogeneity. Improved understanding of the relationships between related disruptive gene events may lead us to improved understanding of shared mechanisms and lead to more focused treatments for individuals with known genetic mutations.

Background Pain management is essential for the care of hospitalized children. Although multiple barriers have been identified that interfere with nurses' ability to provide optimal pain management, it is not known how pervasive are these barriers across the United States. Aims This study is the third in a series of studies examining barriers to pediatric pain management. The aim of this study was to examine barriers in different organizations using the same tool during the same period of time. Settings/Participants A sample of 808 nurses from three pediatric teaching hospitals responded to a survey addressing barriers to optimal pain management for children. Results Barriers unanimously identified as being most significant included inadequate or insufficient physician medication orders, insufficient time allowed to premedicate before procedures, insufficient premedication orders before procedures, and low priority given to pain management by medical staff. Conclusions Barriers identified as the most and least significant were similar regardless of hospital location. Revealing similar barriers across multiple pediatric hospitals provides direction for nurses trying to provide solutions to these pain management barriers.

The structural dependence of the photo-physical properties of substituted 2,3-distyryl (23DSI) indoles were studied using several spectroscopic techniques including steady-state UV-VIS spectroscopy, steady-state fluorescence spectroscopy, steady-state excitation spectroscopy, time correlated single photon counting (TCSPC) spectroscopy, and time-resolved fluorescence upconversion spectroscopy (TRFLS). Each of 23DSI derivatives investigated showed distinct fluorescence emission and UV-VIS spectra, indicating strong structural dependence of the emission and the excitation. The UV-VIS spectra of the 23DSI derivatives showed three main identical absorption bands with minor deviations in the absorbance caused by substituent groups on the distyryl rings. The time-resolved fluorescence up-conversion studies indicated that the fluorescence undergoes a mono-exponential decay whereas the calculated fluorescence lifetime showed relatively short fluorescence lifetimes of approximately 1 ns. All of the 23DSI derivatives showed two-photon absorption upon direct excitation of 1.6 W laser pulses at 800 nm. These studies suggest that the substituents, attached to distyryl core, are capable of boosting or hindering fluorescence intensities by distorting the π-conjugation of the 23DSI molecule. Our studies showed that 23DSI (p-F) has the highest fluorescence emission quantum yield. Theoretical calculations for the ground state of 23DSI derivatives confirmed differences in electron densities in 23DSI derivatives in the presence of different substituent attachments. The excellent fluorescence emission, high fluorescence quantum yield and two-photon absorption properties of these 23DSI molecules make them attractive candidates for potential applications in the fields of biological imaging, biomedicine, fluorescent probes, and photodynamic inactivation (PDI). B. subtilis samples, treated with micro molar solutions of 23DSI (p-OCH3) and 23DSI (p-CH3), showed very effective photodynamic inactivation (PDI) upon irradiation with white light.

This study used signal-to-noise ratios to assess the effects of increasing Itrax XRF instrument parameters, namely tube voltage, tube current and exposure time, on XRF spectra and measurement repeatability. Tests were performed on cores from British and Irish floodplains. Seven combinations of tube voltage and current and six exposure times were compared using signal-to-noise ratios for eight target elements. Signal-to-noise ratios may be substantially improved by selecting instrument parameters, particularly tube voltage, for specific target elements. They can also be used to assess element profile suitability for interpretation by comparison with the limit of quantification. Repeatability was assessed using the standard deviation of measurements in nine repeat scans. The variation in element levels in the majority of profiles is considerably greater than the variability in individual measurements.

Low empathy is a key feature of the Dark Triad traits of narcissism, psychopathy, and Machiavellianism. Nevertheless, prior research, which has used mostly small samples with single measures of each construct, has produced mixed findings. The present study tested associations between Dark Triad traits and empathy using (a) a large sample (N = 1035), (b) multiple measures of each construct, and (c) structural equation modeling. Dark Triad traits, modeled as latent variables using three indicator measures each, were regressed onto two dimensions of empathy—emotional (feeling what others feel) and cognitive (knowing what others think)—which were also modeled as latent variables using three indicator measures each. The model fit the data well. All three Dark Triad traits were associated with low emotional empathy, but the association with narcissism was significantly weaker than associations with psychopathy or Machiavellianism. Psychopathy was unrelated to cognitive empathy, whereas narcissism and Machiavellianism were both positively related to cognitive empathy. The present findings provide a more nuanced and comprehensive theoretical contribution to the links between empathy and the Dark Triad traits.

Advances in sequencing technology have significantly expanded our understanding of the genetics of autism and neurodevelopmental disorders (NDDs). Continued technological improvements and cost reductions have now shifted the focus to investigations into the functional noncoding portions of the genome. There is a patient trend toward an excess of de novo and potentially disruptive mutation among conserved noncoding sequences implicated in the regulation of genes. The signals become stronger when restricting to genes already implicated in NDDs, but de novo mutation in such elements is estimated to account for

Graphical abstract Abstract The development of gene editing technologies, especially the CRISPR-Cas9 system, has been pivotal for understanding the functional role of proteins. Rapid and efficient genotyping methods are necessary to screen for generated mutations and streamline the isolation of homozygotes. CRISPR-Cas9 system targeting a single site in the gene typically results in small indels. Many genotyping methods utilize the heteroduplex that is formed when wild-type and mutant amplicons with small indels anneal during PCR creating a bubble due to mismatched strands. These methods include T7 endonuclease/Cel-I assay, high resolution melting (HRM) analysis, and heteroduplex mobility assay (HMA). Our protocol explains a simple, two step method of a mixing HMA (mHMA) to identify homozygous mutants, a modification of the previously published HMA. We have utilized the mHMA for screening and genotyping numerous CRISPR generated models. The mHMA method to differentiate homozygous wild type from homozygous mutant animals eliminates - • DNA sequencing, even with small indels that can be difficult to discern on a gel. • additional enzymatic reaction steps, such as with the T7EI/Cel-I assay. • specialized equipment and analysis tools, such as with HRM analysis.

Summary The basic mechanisms underlying noxious cold perception are not well understood. We developed Drosophila assays for noxious cold responses. Larvae respond to near-freezing temperatures via a mutually exclusive set of singular behaviors–in particular, a full-body contraction (CT). Class III (CIII) multidendritic sensory neurons are specifically activated by cold and optogenetic activation of these neurons elicits CT. Blocking synaptic transmission in CIII neurons inhibits CT. Genetically, the transient receptor potential (TRP) channels Trpm, NompC, and Polycystic kidney disease 2 (Pkd2) are expressed in CIII neurons, where each is required for CT. Misexpression of Pkd2 is sufficient to confer cold responsiveness. The optogenetic activation level of multimodal CIII neurons determines behavioral output, and visualization of neuronal activity supports this conclusion. Coactivation of cold- and heat-responsive sensory neurons suggests that the cold-evoked response circuitry is dominant. Our Drosophila model will enable a sophisticated molecular genetic dissection of cold nociceptive genes and circuits.

A wide range of methods are commonly used to measure deposited fine sediment and quantify substrate quality in rivers as part of bioassessment or monitoring programmes. In this laboratory-based experiment known amounts of three sediment types (sand, topsoil, peat) were added to mesocosms and four methods of measuring deposited fine sediment; turbidity, estimation of released sediment, Turner–Hillis deposited sediment sampler (DSS) and visual estimation of % surface cover were evaluated. The objective of the study was to evaluate which of these methods for estimating deposited sediment best discriminates between levels of deposited fine sediment added and assesses the effects of inter-observer variability between % surface cover estimations. While turbidity measurement and the resuspension method were strongly related to levels of added sediment, it proved difficult using the two methods to resolve differences between adjacent levels of added sediment e.g. 50 g and 100 g. Surface cover estimations were also strongly related to added sediment levels and were better able to distinguish between adjacent levels of added sediment. Furthermore, we found no significant differences between the % surface cover estimations between observers. Results from this laboratory experiment strongly endorse the use of visual estimation of surface cover in field studies. Further work evaluating the turbidity and re-suspension methods under field conditions would also be beneficial.

An ongoing research challenge is the detection of biological responses to elevated sediment and the identification of sediment-specific bioassessment metrics to evaluate these biological responses. Laboratory mesocosms and field observations in rivers in Ireland were used to evaluate the relationship between a range of biological and sediment metrics and to assess which biological metrics were best at discerning the effects of excess sediment on macroinvertebrates. Results from the mesocosm study indicated a marked decrease in the abundance of sensitive taxa with increasing sediment surface cover. % EPT (Ephemeroptera, Plecoptera, Trichoptera) and % E abundances exhibited the strongest negative correlation with sediment surface cover in the mesocosm study. The field study revealed that % EPT abundance was most closely correlated with % sediment surface cover, explaining 13% of the variance in the biological metric. Both studies revealed weaker relationships with a number of other taxonomy-based metrics including total taxon abundance, total taxon richness and moderate relationships with the Proportion of Sediment-sensitive Invertebrates metric (PSI). All trait-based metrics were poorly correlated with sediment surface cover in the field study. In terms of sediment metrics, % surface cover was more closely related to biological metrics than either re-suspendable sediment or turbidity. These results indicate that % sediment surface cover and % EPT abundance may be useful metrics for assessing the effect of excessive sediment on macroinvertebrates. However, EPT metrics may not be specific to sediment impact and therefore when applied to rivers with multiple pressures should be combined with observations on sediment cover.

Salmonella bacteria may internalize into tomato pulp when warm tomatoes from the field are submerged into colder water. Several washing steps may follow the initial washing and packing of tomatoes at the packinghouses; the potential for internalization into tomatoes in subsequent washing steps when tomatoes have a cooler pulp temperature is unknown. Our objective was to evaluate Salmonella internalization into mature green and red tomatoes with ambient (21°C) and refrigeration (4°C) pulp temperatures when they were submerged into water at various temperature differentials, simulating repacking and fresh-cut operations. Red (4°C and 21°C) and mature green (21°C) tomatoes were submerged (6 cm) into a six-strain Salmonella cocktail (6 log CFU/ml) and maintained at ±5 and 0°C temperature differentials for varying time intervals, ranging from 30 s to 5 min. Following submersion, tomatoes were surface sterilized using 70% ethanol, the stem abscission zone and blossom end epidermis were removed, and cores were recovered, separated into three segments, and analyzed. Salmonella populations in the segments were enumerated by most probable number (MPN). The effects of temperature differential and maturity on Salmonella populations were analyzed; results were considered significant at a P value of ≥0.5. Internalized populations were not significantly different (P ≥0.5) across temperature differentials. Salmonella internalization was seen in tomatoes under all treatment conditions and was highest in the segment immediately below the stem abscission zone. However, populations were low (typically1 log MPN per segment) and varied greatly across temperature differentials. This suggests that the temperature differential between tomatoes and water beyond the initial packinghouse may be less important than submersion time in Salmonella internalization.

Unrestricted cattle access to rivers and streams represent a potentially significant localised pressure on freshwater systems. However there is no consensus in the literature on the occurrence and extent of impact and limited research has examined the effects on aquatic biota in the humid temperate environment examined in the present study. Furthermore, this is one of the first times that research consider the potential for cattle access impacts in streams of varying water quality in Northern Europe. We investigated the effects of cattle access on macroinvertebrate communities and deposited fine sediment levels, in four rivers of high/good and four rivers of moderate water quality status which drain, low gradient, calcareous grassland catchments in Ireland. We assessed the temporal variability in macroinvertebrates communities across two seasons, spring and autumn. Site specific impacts were evident which appeared to be influenced by water quality status and season. All four high/good water status rivers revealed significant downstream changes in community structure and at least two univariate metrics (total richness and EPT richness together with taxon, E and EPT abundance). Two of the four moderate water status rivers showed significant changes in community structure, abundance and richness metrics and functional feeding groups driven in the main by downstream increases in collectors/gatherers, shredders and burrowing taxa. These two moderate water status rivers had high or prolonged livestock activity. In view of these findings, the potential for some of these sites to achieve at least high/good water quality status, as set out in the EU Water Framework Directive, may be compromised. The results presented highlight the need for additional research to further define the site specific factors and livestock management practices, under different discharge conditions, that increase the risk of impact on aquatic ecology due to these cattle-river interactions.

The majority of U.S. nonmarital births today are to cohabiting couples. This study focuses on transitions to cohabitation or marriage among pregnant unmarried women during the period between conception and birth. Results using the newly-released 2006–2010 National Survey of Family Growth show that nonmarital pregnancy is a significant precursor to cohabitation before childbirth (18 percent), exceeding transitions to marriage (5 percent) by factor of over three. For pregnant women, the boundaries between singlehood, cohabitation, and marriage are highly fluid. The results also reveal substantial variation in post-conception cohabiting and marital unions; e.g., disproportionately low percentages of black single and cohabiting women transitioned into marriage, even when conventional social and economic risk factors are controlled. The multivariate analyses also point to persistent class differences in patterns of family formation, including patterns of cohabitation and marriage following conception. Poorly educated women, in particular, are much more likely to become pregnant as singles living alone or as partners in cohabiting unions. But compared with college-educated women, pregnancies are less likely to lead to either cohabitation or marriage. This paper highlights the conceptual and technical challenges involved in making unambiguous interpretations of nonmarital fertility during a period of rising nonmarital cohabitation.

Radiotherapy has been used in the treatment of malignancy for more than 100 years. Ionizing radiation damages cancerous cells leading to cell death. Treatment may be delivered externally or internally. The radiotherapy planning process includes a number of key steps to ensure accurate and safe delivery of treatment. There are a number of strategies available to improve radiotherapy, either exploiting radiobiology aspects or through advances in technology. The field of radiotherapy is exciting and evolving rapidly, with the aim of these advances to improve the outcome of patients treated for malignancy.

Background Approximately 40% of pts with HR+, HER2– ABC have mutations (mut) in PIK3CA, which encodes α-PI3K and leads to PI3K pathway hyperactivation and potentially ET resistance. ALP is a selective inhibitor of α-PI3K that, in combination with fulvestrant (FUL), significantly improved median progression-free survival (PFS) vs placebo + FUL in pts with PIK3CA-mut, HR+ HER2– ABC in the phase 3 SOLAR-1 trial (11.0 vs 5.7 mo, respectively; HR 0.65; 95% CI, 0.50-0.85; P Trial design BYLieve includes women (any menopausal status) and men with PIK3CA-mut, HR+, HER2– ABC and evidence of tumor progression on prior tx. Cohorts A and B comprise pts who received a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) + ET as their last tx. With the adoption of Amendment 3, a new cohort (C) enrolls pts who had systemic chemotherapy or ET as last prior tx and who failed aromatase inhibitor (AI) in the adjuvant or metastatic setting. In the advanced setting, ≤2 anticancer tx (including ≤1 chemotherapy) are allowed. Pts must have ≥1 measurable lesion per RECIST criteria or ≥ 1 predominantly lytic bone lesion. Key exclusion criteria include prior PI3Ki tx and type 1 or uncontrolled type 2 diabetes. Study tx comprises: Cohort A (prior CDK 4/6i + AI), ALP 300 mg once daily (qd) + FUL 500 mg Q28d + C1d15; Cohort B (prior CDK 4/6i + FUL), ALP 300 mg qd + LET 2.5 mg qd; Cohort C, ALP 300 mg qd + FUL 500 mg Q28d + C1d15. The primary endpoint is the proportion of pts free of progression at 6 mo per local investigator assessment for each cohort. Secondary endpoints include PFS, PFS2, ORR, and CBR. Safety and tolerability will also be assessed, including fasted or random blood glucose levels (non-fasted). Tumor tissue and circulating tumor DNA are collected for biomarker assessments. The study is ongoing and currently recruiting pts, with increase in planned overall enrollment from 160 to 340 pts. Clinical trial identification NCT03056755. Editorial acknowledgement Medical editorial assistance was provided by Joe Hodgson of Healthcare Consultancy Group, LLC, and funded by Novartis Pharmaceuticals Corporation. Legal entity responsible for the study Novartis Pharmaceuticals Corporation. Funding Novartis Pharmaceuticals Corporation. Disclosure E. Ciruelos: Advisory / Consultancy, Speaker and consultant fee: Novartis, Roche, Pfzier, Lilly. T. Bachelot: Research grant / Funding (self), Research grant: Novartis; Research grant / Funding (self): Roche; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Pfzier. S. Chia: Advisory / Consultancy, Research grant / Funding (institution), Payment to the institution for conducting clinical trials. Honorarium to myself for advisory boards.: Novartis; Advisory / Consultancy, Research grant / Funding (institution), Payment to the institution for conducting clinical trials. Honorarium to myself for advisory boards.: Pfzier. D. Juric: Advisory / Consultancy, Scientific Advisory Board: Novartis, Genentech, Eisai, Ipsen, EMD Serono. N. Turner: Advisory / Consultancy: AstraZeneca, BMS, Lilly, MSD, Novartis, Pfizer, Roche/Genentech, Tesaro, Bicycle Therapeutics; Research grant / Funding (self): AstraZeneca, BioRad, Pfizer, Roche/Genentech, Clovis, Guardant Health. A. Ridolfi: Full / Part-time employment: Novartis. N. Sophos: Full / Part-time employment: Novartis. B. Cooper: Full / Part-time employment: Novartis. A. Thuerigen: Full / Part-time employment: Novartis. H.S. Rugo: Research grant / Funding (institution): Pfizer, Merck, Novartis, Lilly, Genentech, OBI, Odonate, Daiichi, Eisai, Seattle Genetics and Macrogenics; Travel / Accommodation / Expenses: Lilly, Mylan, Pfizer, Amgen, Merck and Puma. All other authors have declared no conflicts of interest.

The ASPMN strongly recommends that infants who are being circumcised must receive optimal pain management. ‘‘If a decision for circumcision is made, procedural analgesia should be provided’’ (AAP, 1999, p. 691). Therefore, it is the position of the ASPMN that optimal pain management must be provided throughout the circumcision process. Furthermore, parents must be prepared for the procedure and educated about infant pain assessment. They must also be informed of pharmacologic and integrative pain management therapies that are appropriate before, during, and after the procedure.

Bacterial biofilms can be beneficial or detrimental, and are capable of forming on virtually any surface. There is a great need for an in situ sensor able to detect and characterize the developmental stages of bacterial biofilms. We have developed an electrochemical approach to detect and characterize bacterial biofilms using polypyrrole (PPy) enhanced flexible biofilm sensors based on organic substrates of Polyethylene terephthalate (PET). PPy films act as a functionalization material on gold electrodes to reduce their electrical impedance thereby enhancing the detection of electrochemical signals. Flexible PET substrates enable sensors to be placed in systems with complex geometries and to be produced using low cost roll-to-roll manufacturing. Measurements of electrochemical impedance spectroscopy (EIS) using the PET flexible biofilm sensors were correlated with fluorescence microscopy using bacteria that express green fluorescent protein (GFP). The biofilm sensors successfully detected the changes of charge transfer resistance and capacitance corresponding to the maturing stages of biofilm development. The charge transfer resistance increases during the early stages of biofilm maturation and decreases in the later stages of development.

The American Society for Pain Management Nursing (ASPMN) has updated its position statement on managing pain in patients with substance use disorders. This position statement is endorsed by the International Nurses Society on Addictions (IntNSA) and includes clinical practice recommendations based on current evidence. It is the position of ASPMN and IntNSA that every patient with pain, including those with substance use disorders, has the right to be treated with dignity, respect, and high-quality pain assessment and management. Failure to identify and treat the concurrent conditions of pain and substance use disorders will compromise the ability to treat either condition effectively. Barriers to caring for these patients include stigmatization, misconceptions, and limited access to providers skilled in these two categories of disorders. Topics addressed in this position statement include the scope of substance use and related disorders, conceptual models of addiction, ethical considerations, addiction risk stratification, and clinical recommendations.

In this issue of Neuron, Han et al. (2014) develop powerful methods to visualize phagocytosis of Drosophila peripheral sensory neuron dendrites. Remarkably, epidermal cells rather than professional phagocytes are the primary mediators of debris clearance, using both familiar and new molecular players.

This paper provides new estimates of changing patterns of serial cohabitation, using data from the 1995 and 2002 National Survey of Family Growth. Serial cohabitation is defined as having multiple premarital cohabiting relationships. Analyses indicate that rates of serial cohabitation increased by nearly 40 percent over the late 1990s and early 2000s, and rates were especially high among young adults and recent marriage cohorts. A large majority of women – 75 percent – nevertheless lived only with men they eventually married. Although rates of serial cohabitation are higher among never-married women than ever-married women, there is little indication that single women – even older single women – have embraced serial cohabitation as an alternative to marriage or even as an intensive kind of dating. The results show that serial cohabitation is heavily concentrated among disadvantaged populations (e.g., women who grew up in single parent families). Early sexual activity and teen childbearing are especially important “risk” factors for serial cohabitation in the never-married population. There is little evidence, however, that recent shifts in the sociodemographic risk profile of the US population have been responsible for observed increases in single-instance or serial cohabitation. Increases in serial cohabitation have been broadly experienced across population groups in America.

Turner, J. N., Macklin, M. G., Jones, A. F., Lewis, H. (2010). New perspectives on Holocene flooding in Ireland using meta-analysis of fluvial radiocarbon dates. CATENA, 82(3), 183-190. Sponsorship: WAG; HEFCW

An ethical dilemma that is not uncommon to encounter when caring for children occurs when parental preference does not appear to be in the child's best interest. Challenges facing the health care team are further amplified when the family's cultural background does not match that of the team. A case study will be used to illustrate the challenges of a pediatric palliative care ethical dilemma further complicated by cultural diversity. Review of the child's medical condition, patient/parent preferences, quality of life, and contextual features will be followed by an analysis and recommendations for resolution of this challenging situation.

Isolation of fetal cells from maternal circulation is the subject of intense research to eliminate the need for currently used invasive prenatal diagnosis procedures. Fetal cells can be isolated using magnetic-activated cell sorting or fluorescence-activated cell sorting, however no technique to specifically isolate and use fetal cells for genetic diagnosis has reached routine clinical practice. This paper demonstrates the use of a micromachined device to separate fetal cells from maternal circulation based on differences in size and deformation characteristics. Nucleated fetal red blood cells range in diameter from 9 to 12 microm can deform and pass through a channel as small as 2.5 microm wide and 5 microm deep. Although the white blood cells range in diameter from 10 to 20 microm, they cannot deform and are retained by the 2.5 microm wide and 5 microm deep channels under our experimental conditions. Fetal cells were isolated from cord blood and DNA analysis confirmed their fetal origin with ruled out maternal contamination.

Hydrogels are useful for linking proteins to solid surfaces because their hydrophilic nature and porous structure help them to maintain these labile molecules in the native functional state. We have developed a method for creating surface-patterned, biofunctionalized hydrogels on glass or silicon, using polyacrylamide and the disulfide-containing polyacrylamide crosslinker, bis(acryloyl)cystamine. Treatment with a reducing agent created reactive sulfhydryl (–SH) groups throughout these hydrogels that were readily conjugated to iodoacetyl biotin and streptavidin (SA). Immobilization efficiency was approximately 1–2% of the total potential binding capacity of the hydrogel. Porosity of the hydrogel was not a limiting factor for SA immobilization, as determined using fluorescence confocal microscopy. Rather, steric hindrance due to the binding of SA decreased the effective porosity near the surface of the hydrogel, restricting access to the rest of the gel. Using microcontact printing, we indirectly patterned SA on the surface of the hydrogel, generating well-resolved feature sizes of 2 μm in width. Through repeated rounds of microcontact printing, multiple, adjacent protein patterns were generated on the surface of the hydrogel. Biotinylated immune complexes and lipid vesicles readily bound to SA-functionalized hydrogels, demonstrating the feasibility of using this hydrogel system to generate complex biofunctionalized surfaces.

As the result of current and historical metal mining, river channels and floodplains in many parts of the world have become contaminated by metal-rich waste in concentrations that may pose a hazard to human livelihoods and sustainable development. Environmental and human health impacts commonly arise because of the prolonged residence time of heavy metals in river sediments and alluvial soils and their bioaccumulatory nature in plants and animals. This paper considers how an understanding of the processes of sediment-associated metal dispersion in rivers, and the space and timescales over which they operate, can be used in a practical way to help river basin managers more effectively control and remediate catchments affected by current and historical metal mining. A geomorphological approach to the management of rivers contaminated by metals is outlined and four emerging research themes are highlighted and critically reviewed. These are: (1) response and recovery of river systems following the failures of major tailings dams; (2) effects of flooding on river contamination and the sustainable use of floodplains; (3) new developments in isotopic fingerprinting, remote sensing and numerical modelling for identifying the sources of contaminant metals and for mapping the spatial distribution of contaminants in river channels and floodplains; and (4) current approaches to the remediation of river basins affected by mining, appraised in light of the European Union's Water Framework Directive (2000/60/EC). Future opportunities for geomorphologically-based assessments of mining-affected catchments are also identified.

In lab-on-a-chip applications, filtration is currently performed prior to sample loading or through pre-cast membranes adhered to the substrate. These membranes cannot be patterned to micrometer resolution, and their adhesion may be incompatible with the fabrication process or may introduce contaminants. We have developed an on-chip separation process using a biocompatible polymer that can be patterned and has controllable molecular rejection properties. We spun cast cellulose acetate (CA) membranes directly onto silicon wafers. Characterization of the molecular flux across the membrane showed that molecular weight and charge are major factors contributing to the membranes' rejection characteristics. Altering casting conditions such as polymer concentration in the casting solution and the quenching-bath composition and/or temperature allowed control of the molecular weight cut-off (MWCO). Three MWCOs; 300, 350, and 700 Da have been achieved for non-linear molecules. Molecular shape is also very important as much higher molecular weight single-stranded DNA was electrophoresed across the membranes while heme with a similar negative charge density was rejected. This was due to DNA's small molecular cross section. This is an important result because heme inhibits polymerase chain reactions (PCR) reducing the detection and characterization of DNA from blood samples.

The current study was undertaken to fabricate a small micro-electrode on-chip to rapidly detect and quantify human CD4+ cells in a minimal volume of blood through impedance measurements made with simple electronics that could be battery operated implemented in a hand held device. The micro-electrode surface was non-covalently modified sequentially by incubation with solutions of protein G′, human albumin, monoclonal mouse anti-human CD4, and mouse IgG. The anti-human CD4 antibody served as the recognition and capture molecule for CD4+ cells present in human blood. The binding of these biomolecules to the micro-electrodes was verified by impedance and cyclic voltammetry measurements. An increase in impedance was detected for each layer of protein adsorbed onto the micro-electrode surface. This process was shown to be highly repeatable. Increased impedance was measured when CD4+ cells were captured on the micro-electrode, and the impedance also increased as the number of captured cells increased. Fluorescence microscopy of captured cells immunolabeled with anti-human CD4, CD8, and CD19 antibodies, and the nuclear label DAPI, confirmed that only CD4+ cells were captured. The results were highly dependent on the specimen preparation method used. We conclude that the on-chip capture system can efficiently quantify the number of CD4+ cells.