Effects of external influences on synthetic cannabinoid trends in New Zealand, 2014 to 2020.

Over the past decade, synthetic cannabinoids have inundated the global market and now form the largest category of new psychoactive substances. Once these chemicals are available on the global market, they can be applied to plant material in a clandestine environment to create an end-product that is smoked by the user. The synthetic cannabinoids AMB-FUBINACA and 5F-ADB were most frequently detected between 2017 and the beginning of 2019. More recently, these two appear to have been replaced by different synthetic cannabinoids. This investigation summarises the recent trends in synthetic cannabinoids detected in New Zealand between 2017 and 2020 and outlines the potential factors influencing these trends.

The identification and quantification of synthetic cannabinoids seized in New Zealand in 2017.

There has been an explosion of new psychoactive substances (NPS) over the past decade, with synthetic cannabinoids comprising one of the more extensive and chemically diverse groups. Synthetic cannabinoids, like other NPS, are continually evolving with slight alterations in chemical structure, which can lead to unintended and harmful effects for the user. Furthermore, the clandestine preparation of plant material containing one or more synthetic cannabinoid can result in an unevenly distributed product, which poses an additional risk to the user of increased doses. This investigation aimed at providing a snapshot of synthetic cannabinoids in New Zealand in 2017, including the concentrations of synthetic cannabinoids in plant material. Overall, ten different synthetic cannabinoids were detected, with AMB-FUBINACA and 5F-ADB comprising the majority of samples analysed. The synthetic cannabinoid AMB-FUBINACA displayed the greatest range of concentration in plant material, from 5 to over 400 g of synthetic cannabinoid per kilogram of plant material. There was also geographical variation in the synthetic cannabinoids depending on where in New Zealand they were seized from.

Effectiveness of the STOPP/START (Screening Tool of Older Persons' potentially inappropriate Prescriptions/Screening Tool to Alert doctors to the Right Treatment) criteria: systematic review and meta-analysis of randomized controlled studies.

WHAT IS KNOWN AND OBJECTIVE: STOPP/START are explicit screening tools that identify potentially inappropriate prescribing in older adults. Our objective was to update our 2013 systematic review that showed limited evidence of impact, using new evidence from randomized controlled trials (RCTs) assessing clinical, humanistic and economic outcomes in older adults. METHODS: We performed a search of PubMed, EMBASE, CINAHL, Web of Science and grey literature for RCTs published in English since the previous review through June 2014. The Cochrane Risk of Bias Tool was used. We performed a meta-analysis on the effect of STOPP on potentially inappropriate medication (PIM) rates and a narrative synthesis on other outcomes. RESULTS AND DISCUSSION: Four RCTs (n = 1925 adults) from four countries were included, reporting both acute (n = 2) and long-term care (n = 2) patients. Studies differed in implementation. Two studies were judged to have low risk, and two to have moderate-to-high risk of bias in key domains. Meta-analysis found that the STOPP criteria reduced PIM rates in all four studies, but study heterogeneity (I(2) = 86·7%) prevented the calculation of a meaningful statistical summary. We found evidence that use of the criteria reduces falls, delirium episodes, hospital length-of-stay, care visits (primary and emergency) and medication costs, but no evidence of improvements in quality of life or mortality. WHAT IS NEW AND CONCLUSION: STOPP/START may be effective in improving prescribing quality, clinical, humanistic and economic outcomes. Additional research investigating these tools is needed, especially in frail elderly and community-living patients receiving primary care.

Simulating backspatter of blood from cranial gunshot wounds using pig models.

Few studies have examined the biomechanical basis for backspatter from cranial gunshot wounds. Backspatter is material which travels against the direction of fire following ejection from a gunshot entrance wound. Our paper focuses on the use of animals for reconstructing this phenomenon. Five live pigs and several slaughtered pigs were shot using either 9 × 19 mm, 115 grain, full metal jacketed ammunition or .22 long rifle, 40 grain, lead, round-nose ammunition. A high-speed camera was used to record the entrance wound formation and backspatter. A small amount of backspattered material was produced with all targets, and blood backspatter was seen in a few cases. However, we conclude that our model provides an understanding of the phenomenon of backspatter and the physical mechanisms associated with it. The various components of the mechanism of backspatter formation are complex and overlap. The principle mechanism observed in pig cranial gunshots was the high-speed impact response of the skin overlying the skull bone. This study has also produced evidence supporting the view that backspatter can result from the splashing of superficial blood if it is already present on the skin. Subcutaneous gas effects have been demonstrated for backspatter from contact shots. There has been no clear evidence of the role of the collapse of a temporary cavity within the brain.

Probing configuration mixing in 12Be with Gamow-Teller transition strengths.

We present a novel technique for studying the quenching of shell gaps in exotic isotopes. The method is based on extracting Gamow-Teller (ΔL=0, ΔS=1) transition strengths [B(GT)] to low-lying states from charge-exchange reactions at intermediate beam energies. These Gamow-Teller strengths are very sensitive to configuration mixing between cross-shell orbitals, and this technique thus provides an important complement to other tools currently used to study cross-shell mixing. This work focuses on the N=8 shell gap. We populated the ground and 2.24 MeV 0+ states in 12Be using the 12B(1+) (7Li, 7Be) reaction at 80 MeV/u in inverse kinematics. Using the ground-state B(GT) value from ß-decay measurements (0.184±0.007) as a calibration, the B(GT) for the transition to the second 0+ state was determined to be 0.214±0.051. Comparing the extracted Gamow-Teller strengths with shell-model calculations, it was determined that the wave functions of the first and second 0+ states in 12Be are composed of 25±5% and 60±5% (0s)4(0p)8 configurations, respectively.

Lifetime measurement of the 2(1)+ state in 20C.

Establishing how and when large N/Z values require modified or new theoretical tools is a major quest in nuclear physics. Here we report the first measurement of the lifetime of the 2(1)+ state in the near-dripline nucleus 20C. The deduced value of τ(2(1)+)=9.8±2.8(stat)(-1.1)(+0.5)(syst) ps gives a reduced transition probability of B(E2; 2(1)+→0(g.s.)+)=7.5(-1.7)(+3.0)(stat)(-0.4)(+1.0)(syst) e2 fm4 in good agreement with a shell model calculation using isospin-dependent effective charges.

Tobramycin pharmacokinetics in patients with cystic fibrosis before and after bilateral lung transplantation.

STUDY OBJECTIVES: To compare the pharmacokinetics (PK) of tobramycin in patients with cystic fibrosis (CF) before and after bilateral lung transplantation, in order to evaluate optimal dosing practices post transplant. DESIGN: Retrospective, single-center, chart review study, in which tobramycin concentrations from CF patients were used to calculate PK parameters, including elimination rate constant, half-life, volume of distribution (Vd), area under the curve (AUC), and clearance before and after lung transplantation. SETTING: Medical school-affiliated teaching hospital. PATIENTS: Eight patients with CF, who received a bilateral lung transplant from January 1, 2005 through August 1, 2009 (4 males, 4 females; mean age 26.3 years). INTERVENTIONS: None. MAIN RESULTS: Sixty-nine sets of pre- (n=52) and post transplant (n=17) tobramycin concentrations were available. PK parameters were significantly altered post transplant. Elimination rate constant decreased 38% from 0.26±0.1 to 0.16±0.1 h(-1) (P<0.001), with a related increase of 200% in half-life from 2.8±0.8 to 8.4±8.7 h (P<0.001). Clearance decreased 25% post transplant from 67.3±32.3 to 50.2±15.9 mL/min (P=0.04). No statistically significant change occurred in AUC or Vd after transplant, although a trend was seen toward increased Vd. Dosage requirements after transplantation were significantly lower, 10.7±2.5 and 7.6±1.6 mg/kg/day, pre and post transplant, respectively (P<0.001). Concentrations were also evaluated in 2 time periods: 0-3 weeks and ≥6 weeks post transplant, based on available data. Clearance and Vd ≥6 weeks post transplant did not significantly differ from pre-transplant values (P=0.28 and 0.54, respectively), suggesting that these changes may be temporary. CONCLUSIONS: The results suggest that tobramycin PK are altered in patients with CF after bilateral lung transplantation, although no clear trend was seen owing to inter-patient variability. We propose that PK parameters should be reassessed during each treatment course post transplant.

Enhanced quadrupole collectivity at N = 40: the case of neutron-rich Fe isotopes.

The transition rates for the 2(1)+ states in (62,64,66)Fe were studied using the recoil distance Doppler-shift technique applied to projectile Coulomb excitation reactions. The deduced E2 strengths illustrate the enhanced collectivity of the neutron-rich Fe isotopes up to N = 40. The results are interpreted using the generalized concept of valence proton symmetry which describes the evolution of nuclear structure around N = 40 as governed by the number of valence protons with respect to Z ≈ 30. The trend of collectivity suggested by the experimental data is described by state-of-the-art shell-model calculations with a new effective interaction developed for the fpgd valence space.

Pollen on grass clippings: putting the suspect at the scene of the crime.

In a case of alleged sexual assault, the pollen content of samples of grass clippings and soil from the suspect's clothing and shoes was compared to that of a sample of grass clippings from the alleged crime scene (a grassy area) to determine whether or not the suspect had been at the scene. The clothing and shoe samples showed a very strong correlation with each other and with the sample from the alleged crime scene in the combination of the different types of pollen present, very strongly supporting the contention that the suspect had been at the scene.

Molecular phylogenetic analysis of evolutionary trends in stonefly wing structure and locomotor behavior.

Insects in the order Plecoptera (stoneflies) use a form of two-dimensional aerodynamic locomotion called surface skimming to move across water surfaces. Because their weight is supported by water, skimmers can achieve effective aerodynamic locomotion even with small wings and weak flight muscles. These mechanical features stimulated the hypothesis that surface skimming may have been an intermediate stage in the evolution of insect flight, which has perhaps been retained in certain modern stoneflies. Here we present a phylogeny of Plecoptera based on nucleotide sequence data from the small subunit rRNA (18S) gene. By mapping locomotor behavior and wing structural data onto the phylogeny, we distinguish between the competing hypotheses that skimming is a retained ancestral trait or, alternatively, a relatively recent loss of flight. Our results show that basal stoneflies are surface skimmers, and that various forms of surface skimming are distributed widely across the plecopteran phylogeny. Stonefly wings show evolutionary trends in the number of cross veins and the thickness of the cuticle of the longitudinal veins that are consistent with elaboration and diversification of flight-related traits. These data support the hypothesis that the first stoneflies were surface skimmers, and that wing structures important for aerial flight have become elaborated and more diverse during the radiation of modern stoneflies.

Locating and identifying posttranslational modifications by in-source decay during MALDI-TOF mass spectrometry.

A technique is described for identifying and locating posttranslational modifications (PTMs) in peptides and proteins of known sequence by interpretation of c(n) ion signals generated by in-source decay during delayed ion extraction in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Sites of phosphorylation in seven synthetic peptides were determined, as was the location of both the heme group and N,N,N-trimethyllysine in yeast cytochrome c. A semi-automated data analysis process facilitates the identification of segments of the sequence on each side of the PTM, permitting its placement at the junction of the segments and definition of the added mass. A graphical display facilitates illustration of both the location and mass of the PTM.

Quality of life assessment in patients undergoing head and neck surgery as evaluated by lay caregivers.

OBJECTIVES/HYPOTHESIS: Rehabilitation following head and neck cancer surgery has steadily moved into the outpatient realm and become dependent on caregivers with no formal medical background (lay caregivers.) Satisfactory rehabilitation and quality of life (QOL) depend on successful relationships between patients and the lay caregivers. This study evaluates the QOL assessments of patients by themselves and their primary lay caregivers before head and neck surgery. STUDY DESIGN: Institutional Review Board-approved study using validated QOL assessment instrument. MATERIALS AND METHODS: The preoperative QOL status in 50 patients undergoing extensive head and neck surgery was evaluated using the self-administered Medical Outcomes Survey Short Form 36 (SF-36). The patient's primary lay caregiver (spouse, child, or friend) completed a similar questionnaire evaluating the patient's status. RESULTS: Thirty-three (66%) questionnaires were returned. Twenty-five (50%) questionnaire sets were successfully completed by both parties and employable for comparison. Sixty percent of the caregivers were within the 90% confidence interval of the patient's assessment for six or more of the eight parameters evaluated by the SF-36. Likewise, caregiver assessments for specific parameters were consistently congruent with patient evaluation, except for the parameters of bodily pain and general health, for which caregivers demonstrated a trend for overrating pain and underestimating general health. Caregivers of the same generation as the patient demonstrated significantly higher congruence (P = .007). Similarly, a trend for higher congruence was noted in patients with recurrent disease. CONCLUSIONS: The importance of the lay caregiver has increased in the era of greater outpatient rehabilitation. This pilot study indicates that QOL assessment by lay caregivers may be examined with existing instruments and highlights QOL parameters critical to both the head and neck surgery patient and his or her primary lay caregiver.

Stability enhancement for peptide analysis by electrospray using the triple quadrupole mass spectrometer.

Electrospray ionization sources, used with triple quadrupole mass spectrometers from PE/Sciex (API III+), Micromass (Quattro II), and Finnigan (TSQ 7000), were modified with a 35-gauge stainless steel needle. The dimensions of the needle were 63 microm i.d. by 145 microm o.d. with variable length, depending on the specific instrument. This modification led to enhanced signal stability, improved signal/noise ratios, and lowered sample consumption for a wide range of peptides. Stable baselines were observed with flow rates in the range of 50 nL/min to 5 microL/min. An alternative design, based on a metal wire housed within a fused silica capillary, led to the most stable signals of all during infusion, but caused excessive peak broadening with capillary chromatography. The Finnigan interface was further modified with an external postcolumn addition tee, used in conjunction with capillary liquid chromatography columns of 30 and 50 microm internal diameter. The best results with the modified Finnigan interface were acquired using the 50-microm column at a flow rate of 150 to 200 nL/min.

Monitoring calcium-induced conformational changes in recoverin by electrospray mass spectrometry.

Recoverin is a calcium-binding protein that regulates the vertebrate photoresponse by inhibiting rhodopsin kinase in response to high calcium concentrations. It is heterogeneously N-acylated by myristoyl and related fatty acyl residues that are thought to act as "calcium-myristoyl switches," whereby, in the presence of Ca2+, the N-terminal acyl group is extended away from recoverin and, in the absence of calcium, it is more closely associated with the protein. Here we use electrospray ionization mass spectrometry (ESI/MS) to examine hydrogen isotopic exchange rates for specific regions of both acylated and nonacylated recoverin in the presence and absence of calcium. The deuterium exchange rates of three regions in the hydrophobic myristoyl binding pocket of acylated recoverin decreased in the absence of calcium. This effect is most likely due to the closer association of the acyl group with the protein under these conditions. In contrast, rates of deuterium incorporation increased in the absence of calcium for other regions, including the two functional calcium-binding sites. In addition to supporting the calcium-myristoyl switch hypothesis, a comparison of the behavior of acylated and unacylated recoverin revealed that the N-acyl group (N-lauroyl or N-myristoyl) exerts a significant stabilizing influence on the dynamics of recoverin. We demonstrate that the new technique of monitoring hydrogen isotopic exchange by ESI/MS can be used to obtain useful information concerning protein structures in solution using smaller amounts of protein and under more physiologically relevant conditions than is typically possible with NMR or X-ray crystallography.

Interpreting DNA mixtures.

The interpretation of mixed DNA stains is explained in the context of likelihood ratios. The probabilities for the mixed-stain profile are evaluated under alternative explanations that specify the numbers of contributors and the profiles of any known contributors. Interpretations based simply on the frequencies with which random members of a population would not be excluded from a mixed-stain profile do not make use of all the information, and may overstate the strength of the evidence against included people. The effects of the numbers of contributors depends on whether all the alleles at a locus are present in the mixed stain. A general equation is given to allow likelihood ratios to be calculated, and includes the "2p" modification suggested by the 1996 NRC report. This modification is not always conservative. A computer program to perform calculations is available.

Direct sequence analysis of proteins by in-source fragmentation during delayed ion extraction.

Continuous segments of amino acid sequence information as long as 41 residues have been deduced by interpretation of matrix-assisted laser desorption/ionization-generated ion signals dominated by Cn fragmentation within the ion source of a linear time-of-flight mass spectrometer utilizing delayed ion extraction. The technique has been applied successively to five proteins of mass 12.2 kDa to 18.3 kDa, yielding segments of continuous sequence as long as 41 residues without the need for prior proteolytic fragmentation. Intact crosslinks such as disulfides or heme linkages interrupt the generation of these data.

Electrocardiographic markers of late sudden death risk in postoperative tetralogy of Fallot children.

Following surgery for tetralogy of Fallot (TOF), children may develop late onset ventricular arrhythmias. Many patients have both depolarization and repolarization abnormalities, including right bundle branch block (RBBB) and QT prolongation. The goal of this study was to improve prospective risk-assessment screening for late onset sudden death. Resting ECG markers including QRS duration, QTc, JTc, and interlead QT and JT dispersion were statistically analyzed to identify those patients at risk for ventricular arrhythmias and sudden cardiac death. To determine predictive markers for future development of arrhythmia, we examined 101 resting ECGs in patients (age 12 +/- 6 years) with postoperative TOF and RBBB, 14 of whom developed late ventricular tachycardia (VT) or sudden death. These ECGs were also compared with an additional control group of 1000 age- and gender-matched normal ECGs. The mean QRS (+/- SD) in the VT group was 0.18 +/- 0.02 seconds versus 0.14 +/- 0.02 seconds in the non-VT group (P < 0.01). QTc and JTc in the VT group was 0.53 +/- 0.05 seconds and 0.33 +/- 0.03 seconds compared with 0.50 +/- 0.03 seconds and 0.32 +/- 0.03 seconds in the non-VT group (P = NS). There was no increase in QT dispersion among TOF patients with VT or sudden death compared with control patients or TOF patients without VT, although JT dispersion was more common in the TOF groups. A prolonged QRS duration in postoperative TOF with RBBB is more predictive than QTc, JTc, or dispersion indexes for identifying vulnerability to ventricular arrhythmias in this population, while retaining high specificity. The combination of both QRS prolongation and increased JT dispersion had very good positive and negative predictive values. These results suggest that arrhythmogenesis in children following TOF surgery might involve depolarization in addition to repolarization abnormalities. Prospective identification of high-risk children may be accomplished using these ECG criteria.

Beta-methylthio-aspartic acid: identification of a novel posttranslational modification in ribosomal protein S12 from Escherichia coli.

Utilizing microscale chemical derivatization reactions and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, we have identified a novel posttranslational modification of aspartic acid, beta-methylthio-aspartic acid. The modified residue is located at position 88 in ribosomal protein S12 from Escherichia coli, a phylogenetically conserved protein that has been implicated in maintaining translational accuracy of the ribosome.

Arginine 75 in the pseudosubstrate sequence of type Ibeta cGMP-dependent protein kinase is critical for autoinhibition, although autophosphorylated serine 63 is outside this sequence.

Autoinhibitory domains in many protein kinases include either a phosphorylatable substrate-like sequence or a pseudosubstrate sequence. This study shows that Ibeta cGMP-dependent protein kinase (cGK) autophosphorylates Ser-63, which is in an atypical cGK substrate sequence (-59AQKQAS-) that is amino-terminal to the pseudosubstrate motif (-74KRQAI-). cGMP increases the rate of autophosphorylation (approximately 0.8 phosphate/cGK monomer) approximately 3-fold. Autophosphorylation is an intramolecular process since it is independent of cGK concentration. cGMP activation of cGK enhances proteolysis within and near the pseudosubstrate site; treatment of dimeric cGK with three proteases produces three cGK monomers (approximately 67-70 kDa each). Their amino-terminal sequences are 75RQAISAEPT-, 76QAISAEPTAF-, and 86DIQDLSXV-, respectively. cGMP stimulates these kinases by 10-, 2.5-, and 1.4-fold, respectively, compared with a 10-fold effect on intact cGK. Increased basal activity accounts for the diminished stimulation. Thus, the primary autophosphorylation site of Ibeta cGK is well outside the pseudosubstrate site, but Arg-75 in the pseudosubstrate site is critical for autoinhibition. Autoinhibition also involves elements that are carboxyl-terminal to Arg-75.

Autophosphorylation of type Ibeta cGMP-dependent protein kinase increases basal catalytic activity and enhances allosteric activation by cGMP or cAMP.

Autophosphorylation of purified bovine Ibeta isozyme of cGMP-dependent protein kinase (Ibeta cGK) in the presence of cGMP or cAMP increased basal kinase activity (-cGMP) as much as 4-fold and reduced the Ka for both cGMP and cAMP; maximum catalytic activity (+cGMP) was not altered. Autophosphorylation proceeded with at least two rate components. The faster rate correlated with phosphorylation of Ser-63. The slower rate, as well as the increase in basal kinase activity and decrease in Ka for cyclic nucleotides, correlated with phosphorylation of Ser-79. Autophosphorylation of either residue was an intramolecular reaction. Autophosphorylation of a proteolytically generated Ibeta cGK monomer lacking amino-terminal residues 1-64 increased basal activity (3-fold) and decreased Ka for cAMP (15-fold). This indicated that autophosphorylation of Ser-79 did not require dimeric cGK and that the phosphorylation of Ser-79 in the monomer was sufficient to alter enzymatic characteristics of Ibeta cGK. These studies suggested that increases in intracellular cGMP or cAMP could result in autophosphorylation of Ibeta cGK, which would increase basal kinase activity as well as the sensitivity of cGK to activation by cGMP or to cross-activation by cAMP. Autophosphorylation could also prolong the increased kinase activity after decline of the second messenger.