An update on MALDI Mass Spectrometry based technology for the analysis of fingermarks - stepping into operational deployment

Since in 2009, when Matrix Assisted Laser Desorption Ionisation Mass Spectrometry Imaging (MALDI MSI) was firstly reported for the molecular mapping of latent fingermarks, the range of information and operational capabilities have steadily increased. Pioneering work from our Fingermark Research Group exploited different modalities, including Profiling (MALDI MSP), tandem mass spectrometry (MS/MS) and Ion Mobility MS/MS; a number of methodologies were also developed to conquer a main challenge, namely profiling the suspect and their actions prior to or whilst committing the crime. Suspect profiling here is no longer based on behavioural science but complements this discipline and the investigations by detecting and visualising the molecular make-up of fingermarks onto the identifying ridges. This forensic opportunity provides the link between the biometric information (ridge detail) and the corpus delicti or intelligence on the circumstances of the crime. In 2013, a review was published covering the research work and developments of four years supported by the Home Office, UK and the local regional Police with some insights (and comparison) into similar research being reported employing other mass spectrometric techniques. The present review is an extensive update on the MALDI MS based methods' achievements, limitations and work in progress; it also offers an outlook on further necessary research into this subject. The main highlights are the increased number of possible information retrievable around a suspect and the more extended compatibility of this technology. The latter has allowed MALDI MS based methods to integrate well with current forensic fingerprinting, leading to the investigation of real police casework

Development of operational protocols for the analysis of primary and secondary fingermark lifts by MALDI-MS Imaging

Eight years of intensive research have demonstrated that Matrix-Assisted Laser Desorption/Ionisation Mass Spectrometry Profiling and Imaging (MALDI-MSI and MSP) are powerful tools to gather intelligence around a suspect lifestyle, directly from the identifying ridges of a latent fingermark. In the past three years, many efforts have been invested into translating laboratory methodologies to the field; this was undertaken by devising protocols either for (a) enabling initial fingermark visualisation, such as through the Dry-Wet method, recovery and subsequent MALDI MS based analysis, or for (b) rendering the MS methodologies compatible with the prior application of commonly employed fingermark enhancement techniques (FET). In the present work a major point of interest concerned the sample treatment of FET visualised-lifted fingermarks and the subsequent MS performance of primary tape lifted fingermarks ("primary lifts") versus secondary tape lifted fingermarks (recovery from the surface a second time following the initial primary lift). This was necessary since it may not always be possible to obtain primary lifts of marks visualised at crime scenes for remote MALDI-MSP and MSI. The work illustrated here has provided methodological insights into establishing how to best treat a few types of developed marks in preparation for MALDI-MSI when presented as both secondary and primary lifts; it was demonstrated, as expected, that primary lifts generally yield much higher quality chemical/physical information and are therefore crucial to maximise chances of suspect identification and of retrieval of chemical intelligence. When analysing secondary lifted marks that have been initially developed using aluminium or carbon powders, any of the trialled sample preparation methodologies can be employed except the Dry-Wet method. In the case of TiO2 powder developed marks, the best ridge coverage was achieved by re-enhancing the mark using the initial powder and spray-coating with MALDI matrix. Primary lifts of fingermarks contaminated with an exogenous substance (used as a reference model) yielded the best ridge detail quality whilst for secondary lifts of natural marks pre-enhanced with aluminium powder, significantly greater intensity of the ion image was observed for the sections subjected to either no further enhancement or re-enhancement using aluminium powder. Keywords: Fingermarks; MALDI; Imaging; powders; lift

Pravastatin for early-onset pre-eclampsia:a randomised, blinded, placebo-controlled trial

Objective: Women with pre-eclampsia have elevated circulating levels of soluble fms-like tyrosine kinase-1 (sFlt-1). Statins can reduce sFlt-1 from cultured cells and improve pregnancy outcome in animals with a pre-eclampsia-like syndrome. We investigated the effect of pravastatin on plasma sFlt-1 levels during pre-eclampsia. Design: Blinded (clinician and participant), proof of principle, placebo-controlled trial. Setting: Fifteen UK maternity units. Population: We used a minimisation algorithm to assign 62 women with early-onset pre-eclampsia (24 +0–31 +6 weeks of gestation) to receive pravastatin 40 mg daily (n = 30) or matched placebo (n = 32), from randomisation to childbirth. Primary outcome: Difference in mean plasma sFlt-1 levels over the first 3 days following randomisation. Results: The difference in the mean maternal plasma sFlt-1 levels over the first 3 days after randomisation between the pravastatin (n = 27) and placebo (n = 29) groups was 292 pg/ml (95% CI −1175 to 592; P = 0.5), and over days 1–14 was 48 pg/ml (95% CI −1009 to 913; P = 0.9). Women who received pravastatin had a similar length of pregnancy following randomisation compared with those who received placebo (hazard ratio 0.84; 95% CI 0.50–1.40; P = 0.6). The median time from randomisation to childbirth was 9 days [interquartile range (IQR) 5–14 days] for the pravastatin group and 7 days (IQR 4–11 days) for the placebo group. There were three perinatal deaths in the placebo-treated group and no deaths or serious adverse events attributable to pravastatin. Conclusions: We found no evidence that pravastatin lowered maternal plasma sFlt-1 levels once early-onset pre-eclampsia had developed. Pravastatin appears to have no adverse perinatal effects. Tweetable abstract: Pravastatin does not improve maternal plasma sFlt-1 or placental growth factor levels following a diagnosis of early preterm pre-eclampsia #clinicaltrial finds

Genome-Wide Meta-Analysis Identifies Regions on 7p21 (AHR) and 15q24 (CYP1A2) As Determinants of Habitual Caffeine Consumption

We report the first genome-wide association study of habitual caffeine intake. We included 47,341 individuals of European descent based on five population-based studies within the United States. In a meta-analysis adjusted for age, sex, smoking, and eigenvectors of population variation, two loci achieved genome-wide significance: 7p21 (P = 2.4×10−19), near AHR, and 15q24 (P = 5.2×10−14), between CYP1A1 and CYP1A2. Both the AHR and CYP1A2 genes are biologically plausible candidates as CYP1A2 metabolizes caffeine and AHR regulates CYP1A2

Receiver development for BICEP Array, a next-generation CMB polarimeter at the South Pole

A detection of curl-type (B-mode) polarization of the primary CMB would be direct evidence for the inflationary paradigm of the origin of the Universe. The Bicep/Keck Array (BK) program targets the degree angular scales, where the power from primordial B-mode polarization is expected to peak, with ever-increasing sensitivity and has published the most stringent constraints on inflation to date. Bicep Array (BA) is the Stage-3 instrument of the BK program and will comprise four Bicep3-class receivers observing at 30/40, 95, 150 and 220/270 GHz with a combined 32,000+ detectors; such wide frequency coverage is necessary for control of the Galactic foregrounds, which also produce degree-scale B-mode signal. The 30/40 GHz receiver is designed to constrain the synchrotron foreground and has begun observing at the South Pole in early 2020. By the end of a 3-year observing campaign, the full Bicep Array instrument is projected to reach σr between 0.002 and 0.004, depending on foreground complexity and degree of removal of B-modes due to gravitational lensing (delensing). This paper presents an overview of the design, measured on-sky performance and calibration of the first BA receiver. We also give a preview of the added complexity in the time-domain multiplexed readout of the 7,776-detector 150 GHz receiver

Analysis of Temperature-to-Polarization Leakage in BICEP3 and Keck CMB Data from 2016 to 2018

The Bicep/Keck Array experiment is a series of small-aperture refracting telescopes observing degree-scale Cosmic Microwave Background polarization from the South Pole in search of a primordial B-mode signature. As a pair differencing experiment, an important systematic that must be controlled is the differential beam response between the co-located, orthogonally polarized detectors. We use high-fidelity, in-situ measurements of the beam response to estimate the temperature-to-polarization (T → P) leakage in our latest data including observations from 2016 through 2018. This includes three years of Bicep3 observing at 95 GHz, and multifrequency data from Keck Array. Here we present band-averaged far-field beam maps, differential beam mismatch, and residual beam power (after filtering out the leading difference modes via deprojection) for these receivers. We show preliminary results of "beam map simulations," which use these beam maps to observe a simulated temperature (no Q/U) sky to estimate T → P leakage in our real data

Observing low elevation sky and the CMB Cold Spot with BICEP3 at the South Pole

BICEP3 is a 520 mm aperture on-axis refracting telescope at the South Pole, which observes the polarization of the cosmic microwave background (CMB) at 95 GHz to search for the B-mode signal from inflationary gravitational waves. In addition to this main target, we have developed a low-elevation observation strategy to extend coverage of the Southern sky at the South Pole, where BICEP3 can quickly achieve degree-scale E-mode measurements over a large area. An interesting E-mode measurement is probing a potential polarization anomaly around the CMB Cold Spot. During the austral summer seasons of 2018-19 and 2019-20, BICEP3 observed the sky with a flat mirror to redirect the beams to various low elevation ranges. The preliminary data analysis shows degree-scale E-modes measured with high signal-to-noise ratio