Assessing the effects of transient weather conditions on airborne transmission risk in naturally ventilated hospitals.

BACKGROUND: Many UK hospitals rely heavily on natural ventilation as their main source of airflow in patient wards. This method of ventilation can have cost and energy benefits, but it may lead to unpredictable flow patterns between indoor spaces, potentially leading to the unexpected transport of infectious material to other connecting zones. However, the effects of weather conditions on airborne transmission are often overlooked. METHODS: A multi-zone CONTAM model of a naturally ventilated hospital respiratory ward, incorporating time-varying weather, was proposed. Coupling this with an airborne infection model, this study assessed the variable risk in interconnected spaces, focusing particularly on occupancy, disease and ventilation scenarios based on a UK respiratory ward. RESULTS: The results suggest that natural ventilation with varying weather conditions can cause irregularities in the ventilation rates and interzonal flow rates of connected zones, leading to infrequent but high peaks in the concentration of airborne pathogens in particular rooms. This transient behaviour increases the risk of airborne infection, particularly through movement of pathogens between rooms, and highlights that large outbreaks may be more likely under certain conditions. This study demonstrated how ventilation rates achieved by natural ventilation are likely to fall below the recommended guidance, and that the implementation of supplemental mechanical ventilation can increase ventilation rates and reduce the variability in infection risks. CONCLUSION: This model emphasises the need for consideration of transient external conditions when assessing the risk of transmission of airborne infection in indoor environments.

Diagnostic accuracy of a decision-support software for the detection of intracranial large-vessel occlusion in CT angiography.

AIM: To investigate the real-world clinical performance of the decision-support software "e-CTA" (e-Stroke Suite, Brainomix Limited, Oxford UK) for the detection of acute intracranial large-vessel occlusion (LVO) on computed tomography (CT) angiography at a UK district general hospital. MATERIALS AND METHODS: The retrospective study included 300 consecutive CT angiograms of the head and neck performed between 8 March 2021 and 20 May 2021. e-CTA findings were recorded and compared with the radiologist report. Cases in which there was disagreement between e-CTA and the radiologist were reviewed by a sub-specialist vascular radiologist as the reference standard. RESULTS: The incidence of intracranial LVO was 7%. e-CTA correctly identified 18 of 21 intracranial proximal LVOs (86%). There were 34 false positives. The sensitivity was 0.86 (95% confidence interval [CI], 0.64-0.97), with specificity of 0.88 (95% CI, 0.83-0.91). The positive predictive value was 0.35 (95% CI, 0.27-0.43). The negative predictive value was 0.99 (95% CI, 0.96-1.00). CONCLUSION: Sensitivity, specificity, and negative predictive values were similar to those reported in the literature (Seker et al., Int J Stroke. 2021; 17:77-82); however, the positive predictive value for e-CTA was significantly lower. In practice, this meant that over half of all reported occlusions by the software were false positives. Radiologists should be aware of these metrics in order to assign appropriate weight to software findings when formulating a report. Differences in population demographics, scanners, CT protocols, and incidence are all factors potentially influencing software accuracy. Local validation testing may help provide accuracy metrics more relevant to individual institutions.

'Big Data' informed drug development: a case for acceptability.

Data, which help inform various stages of drug product development, are increasingly being collected using newer, more novel platforms, such as mobile applications, and analysed computationally as much larger 'Big Data' data sets, revealing patterns relating to human behaviour and interactions. Medicine acceptability gauges the ability and willingness of patients to take their dosage forms. It has become a crucial human component of drug product design. Vouching for the age appropriateness of medicinal products, acceptability related data are now expected by regulatory bodies. Shifting from traditional paper-based to electronic data-gathering platforms will allow the pharmaceutical industry to collect real-world, real-time, clinically relevant data, capable of informing current and future drug product development, reducing time and cost, and setting foundations for patient-centric drug product design.

Identification of stable genes in the corpus luteum of lactating Holstein cows in pregnancy and luteolysis: Implications for selection of reverse-transcription quantitative PCR reference genes.

In lactating dairy cattle, the corpus luteum (CL) is a dynamic endocrine tissue vital for pregnancy maintenance, fertility, and cyclicity. Understanding processes underlying luteal physiology is therefore necessary to increase reproductive efficiency in cattle. A common technique for investigating luteal physiology is reverse-transcription quantitative PCR (RT-qPCR), a valuable tool for quantifying gene expression. However, reference-gene-based RT-qPCR quantification methods require utilization of stably expressed genes to accurately assess mRNA expression. Historically, selection of reference genes in cattle has relied on subjective selection of a small pool of reference genes, many of which may have significant expression variation among different tissues or physiologic states. This is particularly concerning in dynamic tissues such as the CL, with its capacity for rapid physiologic changes during luteolysis, and likely in the less characterized period of CL maintenance during pregnancy. Thus, there is a clear need to identify reference genes well suited for the bovine CL over a wide range of physiological states. Whole-transcriptome RNA sequencing stands as an effective method to identify new reference genes by enabling the assessment of the expression profile of the entire pool of mRNA transcripts. We report the identification of 13 novel putative reference genes using RNA sequencing in the bovine CL throughout early pregnancy and luteolysis: RPL4, UQCRFS1, COX4I1, RPS4X, SSR3, CST3, ZNF266, CDC42, CD63, HIF1A, YWHAE, EIF3E, and PPIB. Independent RT-qPCR analyses were conducted confirming expression stability in another set of CL tissues from pregnancy and regression, with analyses performed for 3 groups of samples: (1) all samples, (2) samples from pregnancy alone, and (3) samples throughout the process of CL regression. Seven genes were found to be more stable in all states than 2 traditional reference genes (ACTB and GAPDH): RPS4X, COX4I1, PPIB, SSR3, RPL4, YWHAE, and CDC42. When CL tissues from pregnant animals alone were analyzed, CST3, HIF1A, and CD63 were also identified as more stable than ACTB and GAPDH. Identification of these new reference genes will aid in accurate normalization of RT-qPCR results, contributing to proper interpretation of gene expression relevant to luteal physiology. Furthermore, our analysis sheds light on the effects of luteolysis and pregnancy on the stability of gene expression in the bovine CL.

Long-term impacts of rising sea temperature and sea level on shallow water coral communities over a ~40 year period.

Effects of combined rising sea temperature and increasing sea level on coral reefs, both factors associated with global warming, have rarely been addressed. In this ~40 y study of shallow reefs in the eastern Indian Ocean, we show that a rising relative sea level, currently estimated at ~11 mm y-1, has not only promoted coral cover but also has potential to limit damaging effects of thermally-induced bleaching. In 2010 the region experienced the most severe bleaching on record with corals subject to sea temperatures of >31 °C for 7 weeks. While the reef flats studied have a common aspect and are dominated by a similar suite of coral species, there was considerable spatial variation in their bleaching response which corresponded with reef-flat depth. Greatest loss of coral cover and community structure disruption occurred on the shallowest reef flats. Damage was less severe on the deepest reef flat where corals were subject to less aerial exposure, rapid flushing and longer submergence in turbid waters. Recovery of the most damaged sites took only ~8 y. While future trajectories of these resilient reefs will depend on sea-level anomalies, and frequency of extreme bleaching the positive role of rising sea level should not be under-estimated.

The free-energy barrier to hydride transfer across a dipalladium complex.

We use density-functional theory molecular dynamics (DFT-MD) simulations to determine the hydride transfer coordinate between palladium centres of the crystallographically observed terminal hydride locations, Pd-Pd-H, originally postulated for the solution dynamics of the complex bis-NHC dipalladium hydride [{(MesIm)2CH2}2Pd2H][PF6], and then calculate the free-energy along this coordinate. We estimate the transfer barrier-height to be about 20 kcal mol(-1) with a hydride transfer rate in the order of seconds at room temperature. We validate our DFT-MD modelling using inelastic neutron scattering which reveals anharmonicity of the hydride environment that is so pronounced that there is complete failure of the harmonic model for the hydride ligand. The simulations are extended to high temperature to bring the H-transfer to a rate that is accessible to the simulation technique.

Imaging the pericardium: appearances on ECG-gated 64-detector row cardiac computed tomography.

Multidetector row computed tomography (MDCT) with its high spatial and temporal resolution has now become an established and complementary method for cardiac imaging. It can now be used reliably to exclude significant coronary artery disease and delineate complex coronary artery anomalies, and has become a valuable problem-solving tool. Our experience with MDCT imaging suggests that it is clinically useful for imaging the pericardium. It is important to be aware of the normal anatomy of the pericardium and not mistake normal variations for pathology. The pericardial recesses are visible in up to 44% of non-electrocardiogram (ECG)-gated MDCT images. Abnormalities of the pericardium can now be identified with increasing certainty on 64-detector row CT; they may be the key to diagnosis and therefore must not be overlooked. This educational review of the pericardium will cover different imaging techniques, with a significant emphasis on MDCT. We have a large research and clinical experience of ECG-gated cardiac CT and will demonstrate examples of pericardial recesses, their variations and a wide variety of pericardial abnormalities and systemic conditions affecting the pericardium. We give a brief relevant background of the conditions and reinforce the key imaging features. We aim to provide a pictorial demonstration of the wide variety of abnormalities of the pericardium and the pitfalls in the diagnosis of pericardial disease.

Coral reefs under rapid climate change and ocean acidification.

Atmospheric carbon dioxide concentration is expected to exceed 500 parts per million and global temperatures to rise by at least 2 degrees C by 2050 to 2100, values that significantly exceed those of at least the past 420,000 years during which most extant marine organisms evolved. Under conditions expected in the 21st century, global warming and ocean acidification will compromise carbonate accretion, with corals becoming increasingly rare on reef systems. The result will be less diverse reef communities and carbonate reef structures that fail to be maintained. Climate change also exacerbates local stresses from declining water quality and overexploitation of key species, driving reefs increasingly toward the tipping point for functional collapse. This review presents future scenarios for coral reefs that predict increasingly serious consequences for reef-associated fisheries, tourism, coastal protection, and people. As the International Year of the Reef 2008 begins, scaled-up management intervention and decisive action on global emissions are required if the loss of coral-dominated ecosystems is to be avoided.

Multidetector row CT angiography of the lower limb arteries: a prospective comparison of volume-rendered techniques and intra-arterial digital subtraction angiography.

AIM: To assess whether multi-detector CT angiograms (MDCTA) of the lower limb arteries, compared with conventional digital subtraction angiograms (DSA), could replace invasive arteriography in patients with symptomatic peripheral arterial disease. MATERIALS AND METHODS: In a prospective comparative analysis of MDCTA and DSA in 44 patients, MDCTA was analyzed using volume-rendered images acquired at a workstation and viewed in tandem with the original axial data. Designated arterial segments were graded according to their degree of stenosis. RESULTS: We found agreement for the degree of stenosis in 88.8% and 85.4% of 1024 segments analysed for two observers. The sensitivity for treatable lesions (>50% stenosis) was 79.1% and 72% with a specificity of 93.3% and 92.6%. DSA failed to visualize 7.3% of segments that were visible with MDCTA. These segments were exclusively downstream to long segment occlusions. CONCLUSION: MDCTA using 4-slice machines is insensitive to detecting significant arterial stenoses in the lower limb arteries. MDCTA is superior to DSA in its visualization of arterial territories downstream to significant occlusive disease.

A comparison of a 'J' wire and a straight wire in successful antegrade cannulation of the superficial femoral artery.

AIMS: To evaluate the success of two different types of wire in common use in their ability to successfully cannulate the superficial femoral artery (SFA) using antegrade puncture. METHODS: 50 consecutive patients in whom antegrade infra-inguinal intervention was planned, underwent common femoral arterial puncture and then cannulation with either a standard 3mm 'J' wire or a floppy tipped straight wire (William Cook-Europe). The frequency with which each type of wire entered the SFA or profunda femoris artery without image guidance was recorded. Further analysis was also made of the success of manipulation of the wire into the SFA following profunda cannulation and the use of alternative guide wires. RESULTS: In 19 out of 25 (76%) patients the 'J' wire correctly entered the SFA without image guidance. Only 5 out of 25 (25%) of straight wires entered the SFA with the initial pass (p < 0.0001). Following further manipulation with the same wire all except 1 'J' wire was successfully negotiated into the SFA. The same was true for only 9 of the remaining straight wires with 11 patients requiring an alternative guide wire. CONCLUSIONS: When performing antegrade cannulation of the SFA a 'J' wire is more likely to be successful than a straight guide wire.

The effect of reporting speed on plain film reporting errors.

AIM: To determine whether reporting plain films at faster rates lead to a deterioration in accuracy. METHODS: Fourteen consultant radiologists were asked to report a total of 90 radiographs in three sets of 30. They reported the first set at the rate they would report normally and the subsequent two sets in two thirds and one half of the original time. The 90 radiographs were the same for each radiologist, however, the order was randomly generated for each. RESULTS: There was no significant difference in overall accuracy for each of the three film sets (p=0.74). Additionally no significant difference in the total number of false-negatives for each film set was detected (p=0.14). However, there was a significant decrease in the number of false-positive reports when the radiologists were asked to report at higher speeds (p=0.003). CONCLUSIONS: When reporting accident and emergency radiographs increasing reporting speed has no overall effect upon accuracy, however, it does lead to less false-positive reports.

Effect of cruciferous vegetable consumption on heterocyclic aromatic amine metabolism in man.

The consumption of cooked meat appears to predispose individuals to colonic cancer and heterocyclic aromatic amines (HA), formed during the cooking of meat, have been suggested as aetiological agents. Consumption of cruciferous vegetables is thought to protect against cancer. To study the effect of cruciferous vegetables on heterocyclic aromatic amine metabolism in man, a three-period, dietary intervention study has been carried out with 20 non-smoking Caucasian male subjects consuming cooked meat meals containing known amounts of these carcinogens. A high cruciferous vegetable diet (250 g each of Brussels sprouts and broccoli per day) was maintained during period 2 but such vegetables were excluded from periods 1 and 3. At the end of each period, subjects consumed a cooked meat meal and urinary excretion of the HA 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) was measured. Following a 12 day period of cruciferous vegetable consumption (period 2), induction of hepatic CYP1A2 activity was apparent from changes in the kinetics of caffeine metabolism. Excretion of MeIQx and PhIP in urine at the end of this period of the study was reduced by 23 and 21%, respectively, compared with period 1. This reduction in excretion is probably due to an increase in amine metabolism that might be expected given the observed increase in CYP1A2 activity, since this enzyme has been shown to be primarily responsible for the oxidative activation of MeIQx and PhIP in man. In period 2, urinary mutagenicity was increased relative to period 1 by 52 and 64% in the absence and presence, respectively, of a human liver microsomal activation system, yet no evidence was found of PhIP adduction to lymphocyte DNA, a potential biomarker of the activation process. After another 12 days without cruciferous vegetables (period 3 of the study), the kinetics of caffeine metabolism had returned to original values but excretion of MeIQx and PhIP was still reduced by 17 and 30%, respectively, and urinary mutagenicity (with metabolic activation) was still elevated compared with period 1. This prolonged response of amine metabolism to the cruciferous vegetable diet, shown especially with PhIP, suggests that enzyme systems other than CYP1A2 are involved and affected by a cruciferous vegetable diet.

Massive pericardial effusion with left-to-right intracardiac shunt.

We describe a 31-year-old man with Down's syndrome who presented with severe chronic hypothyroidism and a massive pericardial effusion. Following partial aspiration of this effusion, he rapidly deteriorated and died. Findings at autopsy revealed him to have an atrioventricular septal defect with shunting at the atrial level. We postulate that, by releasing extrinsic pressure on his right heart by the aspiration, there was sudden shunting of blood from left-to-right, resulting in hypotension, shock, and subsequent death. We highlight the difficulties in management of such a case, and suggest alternative strategies.

Lack of effect of furfural on unscheduled DNA synthesis in the in vivo rat and mouse hepatocyte DNA repair assays and in precision-cut human liver slices.

The ability of furfural to induce unscheduled DNA synthesis (UDS) in hepatocytes of male and female B6C3F(1) mice and male F344 rats after in vivo administration and in vitro in precision-cut human liver slices has been studied. Preliminary toxicity studies established the maximum tolerated dose (MTD) of furfural to be 320 and 50 mg/kg in the mouse and rat, respectively. Furfural was dosed by gavage at levels of 0 (control), 50, 175 and 320 mg/kg to male and female mice and 0, 5, 16.7 and 50 mg/kg to male rats. Hepatocytes were isolated by liver perfusion either 2-4 h or 12-16 h after treatment, cultured in medium containing [3H]thymidine for 4 h and assessed for UDS by grain counting of autoradiographs. Furfural treatment did not produce any statistically significant increase or any dose-related effects on UDS in mouse and rat hepatocytes either 2-4 h or 12-16 h after dosing. In contrast, UDS was markedly induced in mice and rats 2-4 h after treatment with 20 mg/kg dimethylnitrosamine and 12-16 h after treatment of mice and rats with 200 mg/kg o-aminoazotoluene and 50 mg/kg 2-acetylaminofluorene (2-AAF), respectively. Precision-cut human liver slices from four donors were cultured for 24 h in medium containing [3H]thymidine and 0-10 mM furfural. Small increases in the net grain count (i.e. nuclear grain count less mean cytoplasmic grain count) observed with 2-10 mM furfural were not due to any increase in the nuclear grain count. Rather, it was the result of concentration-dependent decreases in the mean cytoplasmic grain counts and to a lesser extent in nuclear grain counts, due to furfural-induced cytotoxicity. In contrast, marked increases in UDS (both net grain and nuclear grain counts) were observed in human liver slices treated with 0.02 and 0.05 mM 2-AAF, 0.002 and 0.02 mM aflatoxin B(1) and 0.005 and 0.05 mM 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. This study demonstrates that furfural does not induce UDS in the hepatocytes of male and female B6C3F(1) mice and male F344 rats after oral treatment at doses up to the MTDs. Moreover, human liver slice studies suggest that furfural is also not a genotoxic agent in human liver.

A novel extrinsic reference method for assessing the vitamin A value of plant foods.

BACKGROUND: The amounts of vitamin A that are metabolically derived from specific carotene-containing foods are largely unknown. OBJECTIVE: We sought to develop an improved method for estimating the metabolic vitamin A potential of provitamin A carotenoids by using [2H4]retinyl acetate (d4-RA) as an extrinsic reference standard. DESIGN: Healthy subjects consumed a standardized test meal containing 6 mg beta-carotene as either raw carrot or spinach, either 20 or 1 g added fat, and 6.0 micromol d4-RA. Concentrations of unlabeled (d0) retinyl esters (RE), labeled (d4) RE, and carotenoids in the plasma triacylglycerol-rich lipoprotein fraction (d < 1.006 kg/L) were determined in serial blood samples with HPLC and gas chromatography-mass spectrometry. Baseline-corrected areas under the curve for d0-RE, d4-RE, and carotenoids were calculated, and the masses of absorbed d0-retinol and carotenes were estimated assuming 80% absorption of the d4-RA reference dose. RESULTS: In trials with ample (20 g) fat (n = 6), 7 +/- 4% of the 6 mg beta-carotene ingested was taken up as beta-carotene plus RE with 0.3 +/- 0.1 mg as retinol. Test meals without carotenes yielded no beta-carotene or d0-RE response and there was no effect of treatment (either fat amount or vegetable, n = 6) on the mean d4-RE area under the curve. The lower-than-expected vitamin A yields were attributed to poor intestinal uptake rather than to low conversion of beta-carotene to RE. CONCLUSION: The triacylglycerol-rich lipoprotein and d4-RA method, which controls for variation in chylomicron kinetics in vivo and RE recovery during analysis, is useful for obtaining quantitative estimates of the vitamin A potential of single meals.

Coral bleaching and mortality on artificial and natural reefs in Maldives in 1998, sea surface temperature anomalies and initial recovery.

The bleaching and subsequent mortality of branching and massive corals on artificial and natural reefs in the central atolls of Maldives in 1998 are examined with respect to sea surface temperature (SST) anomalies. SST normally peaks in April-May in Maldives. The UK Meteorological Office's Global sea-Ice and SST data set version 2.3 b shows that in 1998 monthly mean SST was 1.2-4 S.D. above the 1950-1999 average during the warmest months (March-June), with the greatest anomaly in May of +2.1 degrees C. Bleaching was first reported in mid-April and was severe from late April to mid-May with some recovery evident by late-May. At least 98% of branching corals (Acroporidae, Pocilloporidae) on artificial structures deployed on a reef flat in 1990 died whereas the majority of massive corals (Poritidae, Faviidae, Agariciidae) survived the bleaching. The pre-bleaching coral community on the artificial reefs in 1994 was 95% branching corals and 5% massives (n = 1589); the post-bleaching community was 3% branching corals and 97% massives (n = 248). Significant reductions in live coral cover were seen at all natural reefs surveyed in the central atolls, with average live coral cover decreasing from about 42% to 2%, a 20-fold reduction from pre-bleaching levels. A survey of recruitment of juvenile corals to the artificial structures 10 months after the bleaching event showed that 67% of recruits (> or = 0.5 cm diameter) were acroporids and pocilloporids and 33% were from massive families (n = 202) compared to 94% and 6%, respectively, in 1990-1994 (n = 3136). Similar post-bleaching dominance of recruitment by branching corals was seen on nearby natural reef (78% acroporids and pocilloporids; 22% massives). A linear regression of April mean monthly SST against year was highly significant (p < 0.001) and suggests a rise of 0.16 degree C per decade. If this trend continues, by 2030 mean April SST in the central atolls will normally exceed the anomaly level at which corals appear there are susceptible to mass bleaching.

Digital imaging considerations for gel electrophoresis analysis systems.

Gel analysis system purchasers have a large variety of digital imaging products to choose from today. Understanding the specifications presented by the manufacturers is important to ensure that the system fits the needs ofthe researcher using the system. The background information contained in this paper explains the terminology and many of the specifications along with their significance.

Macrochelation, cyclometallation and G-quartet formation: N3- and C8-bound PdII complexes of adenine and guanine.

The reactions of Pd(II) ions with a series of chelate-tethered derivatives of adenine and guanine have been studied and reveal a difference in the reactivity of the purine bases. Reactions of [PdCl2(MeCN)2] and A-alkyl-enH x Cl (alkyl = propyl or ethyl, A adenine, en = ethylenediamine) yield the monocationic species [PdCl(A-N3-Et-en)]+ (1) and [PdCl(A-N3-Pr-en)]+ (2). Both involve co-ordination at the minor groove site N3 of the nucleobase as confirmed by single-crystal X-ray analysis. Reactions with the analogous G-alkyl-enH x Cl derivatives (G=guanine, alkyl = ethyl or propyl) were more complex with a mixture of species being observed. For G-Et-en HCI a product was isolated which was identified as [PdCl(G-C8-Et-en)]+ (3). This compound contains a biomolecular metal-carbon bond involving C8 of the purine base. Crystallography of a product obtained from reaction of G-Pr-enH x Cl and [Pd(MeCN)4][NO3]2 reveals an octacationic tetrameric complex (4), in which each ligand acts to bridge two metal ions through a combination of a tridentate binding mode involving the diamine and N3 and monodentate coordination at N7.

Diffuse X-ray scattering from benzil, C(14)H(10)O(2): analysis via automatic refinement of a Monte Carlo model.

A recently developed method for fitting a Monte Carlo computer-simulation model to observed single-crystal diffuse X-ray scattering has been used to study the diffuse scattering in benzil, diphenylethanedione, C(6)H(5)-CO-CO-C(6)H(5). A model involving 13 parameters consisting of 11 intermolecular force constants, a single intramolecular torsional force constant and a local Debye-Waller factor was refined to give an agreement factor, R = [summation operator omega(Delta I)(2)/summation operator omega I(obs)(2)](1/2), of 14.5% for 101,324 data points. The model was purely thermal in nature. The analysis has shown that the diffuse lines, which feature so prominently in the observed diffraction patterns, are due to strong longitudinal displacement correlations. These are transmitted from molecule to molecule via a network of contacts involving hydrogen bonding of an O atom on one molecule and the para H atom of the phenyl ring of a neighbouring molecule. The analysis also allowed the determination of a torsional force constant for rotations about the single bonds in the molecule. This is the first diffuse scattering study in which measurement of such internal molecular torsion forces has been attempted.

Introduction to NMR of proteins.

This unit aims to overview the application of NMR spectroscopy to proteins. It is not intended to provide an exhaustive "how to" guide, but rather to give a flavor of both well-established and emerging NMR techniques used in the elucidation of protein structure. It starts with a brief introduction to the basic principles of NMR and the information provided by this technique, and goes on to discuss the instrumentation involved, spectral assignment methods for small and large proteins, and the utility of other spin active nuclei (e.g., (13)C and (15)N) to aid assignment of the latter.