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D. V. Gusak and E. V. Karnaukh
Theor. Probability and Math. Statist. 99 (2020), 77-89.
Abstract, references and article information

Cédric Arhancet
Proc. Amer. Math. Soc. 148 (2020), 2551-2563.
Abstract, references and article information

The challenges, for Hong Kong, are as much local as they are global. I know many of you are concerned about the recent social unrest here in Hong Kong, about whether it is affecting our financial market and whether there has been outflow of funds.

First of all, there's the obvious: Hong Kong is undergoing a time of unprecedented turbulence. Dissension has gripped our community for months now. That said, we are working to address and respond to those concerns, determined to find a path to peace, harmony and renewed prosperity in 2020.

We have been making progress. But there is still much to be done before we can put this testing time behind us.

Competitive advantages

What I can tell is that the advantages Hong Kong has long been recognised for are still very much with us, and they are not going anywhere anytime soon.

They begin with our enviable location, at the heart of Asia. Which means that Hong Kong is fully plugged into the round-the-clock global financial trading cycle. We provide certain and seamless connectivity with the financial hubs of Europe and North America, as well as those in the Middle East and across Asia.

Hong Kong is blessed with the dual advantages of "one country, two systems". The rule of law, an independent judiciary and an unshakable adherence to free enterprise are among Hong Kong's core values.

We offer businesses from the Mainland and all over the world - more than 9,000 at last count - a level-playing field, a competitive market, whatever their businesses, whatever their investments. Our linked exchange rate system remains solid, our currency fully convertible and capital flowing in and out freely, as enshrined in Article 112 of the Basic Law. Our capital markets are deep and liquid.

Despite our external and domestic challenges, Hong Kong's financial market remains stable. Our banking system continues to run smoothly and with ample liquidity.

The figures speak for themselves. In 2019, Hong Kong again topped the world in funds raised through IPOs - some US$40 billion worth. This is the seventh time we have come first in the past 11 years.

Our stock market's capitalisation is about US$4.9 trillion. That's more than 13 times Hong Kong's GDP.

As at end November 2019, bank deposits in both Hong Kong dollars and foreign currencies continued to increase over the same period last year, totalling US$1.8 trillion.

Our exchange rate remains stable. These and other measures reflect the integrity of Hong Kong's financial and legal system, the confidence it conveys, even as we face formidable external and domestic shocks.

In September last year, the Global Financial Centres Index once again ranked Hong Kong among the world's top three financial centres, behind only New York and bearing in on London.

Last October, the World Economic Forum's Global Competitiveness Report ranked our financial system top in the world, while the World Bank rated Hong Kong the third-easiest place to do business.

Hong Kong is still very much the largest offshore renminbi business hub in the world.

We are, as well, the premier asset and wealth management centre. Apart from exempting onshore and offshore funds from profits tax, we are considering introducing a more competitive tax arrangement to attract private equity funds to domicile in Hong Kong.  

The insurance industry is equally important. We have, after all, the highest concentration of insurers in Asia - more than 160 at the end of September. And we will enable the issuance of insurance-linked securities, expanding the insurable risks of captive insurers in Hong Kong.

On the taxes front, we already have the world's most business-friendly tax system, according to Paying Taxes 2020, a report produced by Pricewaterhouse Coopers and the World Bank. Still, we plan to provide tax relief to promote the development of marine insurance and the underwriting of specialty risks in Hong Kong.

Green finance is our policy priority going forward. Green bonds issued and arranged in Hong Kong increased over 200% to US$11 billion in 2018 as compared to the previous year.

That was followed by our inaugural government green bond issuance of US$1 billion last May. And we plan to issue more, and encourage more entities to arrange financing for their green projects right here in Hong Kong.

Fintech is another area where we strive to excel.

Looking at the big picture, the International Monetary Fund (IMF)'s latest projection of global economic growth this year has been adjusted downward to 3.4%. Growth in Asia, however, will continue to outperform the rest of the world.

The IMF forecasts the Mainland economy to grow by 5.8% in 2020, down slightly but still far and away leading most other jurisdictions.

Robust financial system

As for Hong Kong, the IMF Staff Report last month commended the resilience of our financial system and linked exchange rate, despite its slowing economy. The IMF's Hong Kong report noted, and I quote, that "robust policy frameworks and ample buffers will help the economy weather the challenges ahead".

The IMF also expressed approval for the Government's wide-ranging policies to support the economy and safeguard financial stability.

While we welcome the IMF's confidence in Hong Kong, I am prepared to roll out further relief measures as necessary.

We will also step up efforts to capitalise on emerging opportunities - not only from green finance and fintech but from the development of the Guangdong-Hong Kong-Macao Greater Bay Area and the Belt & Road Initiative, which demonstrates Hong Kong's uniqueness and irreplaceable position in the Mainland's national and economic development strategy.

Hong Kong is, and will remain, the business bridge between the Mainland and the rest of the world. Count on Hong Kong, as always, to be your partner, to help you build your business in the Mainland, throughout the Asian region and around the world. Count on Hong Kong to connect you with abundant capital and continuing opportunities.

Financial Secretary Paul Chan gave these remarks at the 13th Asian Financial Forum keynote luncheon on January 13.

The parking fees of 12 government public car parks will be frozen at their existing levels for one year from June 1, the Transport Department announced today.

In reviewing the parking fees, the department said it considered the inflation rate, private car park charges and usage of the government car parks.

Having considered the impact on the economy brought by the COVID-19 pandemic as well as the impact on usage of the car parks, the department decided to maintain the parking fees at existing levels.

The 12 car parks are Kennedy Town Car Park, Rumsey Street Car Park, Star Ferry Car Park, City Hall Car Park, Tin Hau Car Park, Shau Kei Wan Car Park, Aberdeen Car Park, Yau Ma Tei Car Park, Sheung Fung Street Car Park, Wong Tai Sin Public Transport Terminus Car Park, Kwai Fong Car Park and Tsuen Wan Car Park.

Click here for details.

Jacob Oleck
Aug 1, 2016; 29:180-184
Pharmacy and Therapeutics

The Hong Kong Special Administrative Region Government has rejected allegations made by certain officials and politicians in the United States, United Kingdom and European Parliament relating to an April 18 arrest operation and other security matters.

In a statement today, the Hong Kong SAR Government said such allegations were totally unfounded and amounted to a serious intervention in Hong Kong's affairs.

The SAR Government strongly disagreed with the grossly irresponsible remarks and expressed deep regret about them.

It pointed out that since its return to the Motherland, the HKSAR has maintained stability and prosperity under the principle of "one country, two systems", exercising "Hong Kong people administering Hong Kong" and a high degree of autonomy in strict accordance with the Basic Law (BL).   

"The Central Government has time and again reiterated that it will unswervingly implement the policy of one country, two systems' and make sure that it is fully applied in Hong Kong without being bent or distorted. 

“How to implement the policy in the HKSAR - an inalienable part of the People's Republic of China (BL Article 1) and a local administrative region of the People's Republic of China which shall enjoy a high degree of autonomy and come directly under the Central People's Government (BL Article 12) - are entirely internal affairs of the People's Republic of China.

“No other state has the right to intervene, directly or indirectly, in those internal affairs.”

The statement noted Hong Kong people enjoy extensive rights and freedoms which are enshrined in the Basic Law. Basic Law Article 4 states that the HKSAR shall safeguard the rights and freedoms of the residents and of other persons in the region in accordance with law. 

“In addition, human rights and freedoms in Hong Kong are fully protected by the Hong Kong Bill of Rights Ordinance and other legislation, and underpinned by an independent judiciary."

The SAR Government said it always respects and protects human rights and freedoms. Any allegation that there has been an erosion in freedoms enjoyed by Hong Kong people is unfounded.

However, these rights are not absolute. As pointed out by the Chief Justice of the Court of Final Appeal at the Ceremonial Opening of the Legal Year 2020: "It is important to understand that the enjoyment of these rights has limits so as not to affect adversely to an unacceptable level the enjoyment by other members of their community of their rights and liberties."

There are clear limits in the law as to the exercise of these rights. When the law is broken, action will be taken in accordance with the criminal justice system.

"We therefore take great exception to comments made by officials and politicians in foreign countries concerning the recent arrests and prosecution of a number of persons for organising and participating in unauthorised assemblies in Hong Kong. 

“The allegation by some that those arrests amounted to an attack on Hong Kong's freedoms and a breach of the BL is absurd and can hardly stand the test of any law-abiding jurisdiction," the statement emphasised.

It also pointed out that Basic Law Article 63 provides that "The Department of Justice of the Hong Kong Special Administrative Region shall control criminal prosecutions, free from any interference." 

Prosecutors have always been discharging this constitutional duty independently and professionally, without fear or favour. Prosecutorial decisions are based on an objective assessment of all admissible evidence and applicable laws, made strictly in accordance with the Prosecution Code which is available to the public.

Cases will not be handled any differently owing to the political beliefs or background of the persons involved.

When law enforcement agencies have completed their investigation, they would seek legal advice from the Department of Justice. The prosecutors would carefully consider the investigation reports and relevant materials submitted. A prosecution would only be commenced if the prosecutor is satisfied that there is sufficient admissible evidence to support a reasonable prospect of conviction.

In short, the well-established procedures of Hong Kong's criminal justice system include the independent investigations by law enforcement agencies, the independent prosecutorial decisions based on the objective assessment of evidence, applicable laws and in accordance with the Prosecution Code, and finally, open trials by an independent judiciary. 

"The guarantee of judicial independence is explicitly set out in the BL and the quality of the judgments of our courts contributes to the much respected judiciary and rule of law in the HKSAR.

"We therefore note with abhorrence certain overseas politicians' request that the HKSAR Government should drop the charges against the arrested individuals. If we were to accede or to be seen to yield to such unreasonable demands, we would not only be unfair and unprofessional but would also act in violation of the spirit of the rule of law – a core value in Hong Kong," the statement added.

The SAR Government remains steadfast to uphold the rule of law. The latest Rule of Law Index 2020 released by the World Justice Project, in which Hong Kong maintains its ranking as No. 5 in the East Asia and Pacific Region and No. 16 globally, several places ahead of the United States, has clearly affirmed Hong Kong's commitment.

On legislating for Basic Law Article 23, the statement said, "The HKSAR Government has the constitutional duty to ensure that the necessary legislation is in place to safeguard national security.

“Having laws in place to protect national security is common in many jurisdictions, and we do not see how any defence of sovereignty and security by a jurisdiction would impact on its local and overseas investment. 

“Coincidentally, it is relevant to note security issues arising from the social unrest last year were part of the causes affecting Hong Kong's score under 'Investment Freedom' according to the US-based Heritage Foundation 2020 Index of Economic Freedom."

As regards enquiries about the role of the Hong Kong & Macao Affairs Office of the State Council (HKMAO) and the Liaison Office of the Central People's Government (LOCPG) in the HKSAR, they represent the Central People's Government to which the HKSAR comes directly under pertaining to Basic Law Article 12. 

These offices have the power and responsibility over the proper and full implementation of the Basic Law and "one country, two systems" in Hong Kong.

It is therefore clearly legitimate for the HKMAO and LOCPG to recently express their concerns over the prolonged paralysis of the Legislative Council House Committee, thereby hindering LegCo's performance of its legislative functions under the Basic Law.

"Any suggestion that those legitimate remarks by the HKMAO and the LOCPG amount to interference only illustrates an ignorance of the constitutional order of the HKSAR and its relationship with the Central Authorities," the SAR Government added.

Secretary for Innovation & Technology Alfred Sit today met representatives of the Hong Kong Science & Technology Parks Corporation (HKSTPC) and research and development centres (R&D) specialising in innovations winning recognition worldwide.

While touring the Hong Kong Science Park, Mr Sit visited the Hong Kong Applied Science & Technology Research Institute, the Logistics & Supply Chain MultiTech R&D Centre, the Nano & Advanced Materials Institute and HKSTPC.

He met representatives of HKSTPC start-ups that specialise in healthcare technology, artificial intelligence, chips, material science and vehicle safety technology. Some start-ups have participated in the StayHomeSafe mobile app.

Mr Sit noted that Science Park is a breeding ground for local innovation and technology that shows tremendous strength.

He emphasised that with the concerted efforts of the HKSTPC and all R&D centres, batches of R&D talent have been nurtured, with their innovations winning recognition worldwide.

Their work has also helped consolidate Hong Kong's R&D strengths, promote applied R&D and foster commercialisation of R&D results, he added.

On the application of technology solutions in fighting the COVID-19 pandemic, the secretary pointed out that the electronic wristbands and StayHomeSafe mobile app used for home quarantine arrangements, the NASK Nanofiber Smart Mask supplied to the Hospital Authority and the CuMask are all R&D achievements from Science Park.

Mr Sit said he hoped that with the collaborative efforts of the HKSTPC and R&D centres, the I&T development in Hong Kong will be further promoted, driving economic development and improving people's livelihood.

VOLUME 295 (2020) PAGES 3285–3300An incorrect graph was used in Fig. 5C. This error has now been corrected. Additionally, some of the statistics reported in the legend and text referring to Fig. 5C were incorrect. The F statistics for Fig. 5C should state Fken(3,16) = 7.454, p < 0.01; FCCCP(1,16) = 102.9, p < 0.0001; Finteraction(3,16) = 7.480, p < 0.01. This correction does not affect the results or conclusions of this work.jbc;295/17/5835/F5F1F5Figure 5C.

Chief Executive Carrie Lam today visited Tai Mo Shan Country Park to inspect its management services amid the COVID-19 epidemic.

She was accompanied by Secretary for the Environment KS Wong and Director of Agriculture, Fisheries & Conservation Dr Leung Siu-fai.

Mrs Lam visited personnel working at the park’s visitor centre and Twisk Country Park Management Centre of Tai Lam Country Park.

She observed how they enhanced campsites and associated facilities, improved hiking trails with natural materials, provided more lookout points for people to enjoy the scenery and strengthened services at visitor centres.

Mrs Lam learnt about the department’s anti-epidemic measures and management work, including running temperature checks on all park visitors.

Noting that the number of visitors in various country parks increased by 25% in February, Mrs Lam praised staff for their commitment to strengthening anti-epidemic work to safeguard public health.

The department enhanced its promotions and public education on anti-epidemic measures and protecting the environment through various means including social media and the networks of partner organisations.

Mrs Lam also visited a refreshment kiosk to learn about its business.

The department has provided rent concessions to all kiosks in country parks and will extend such relief measures until September this year to help shop operators during these difficult times. 

Mrs Lam said she appreciated the kiosk’s efforts to protect the environment and reduce waste and disposable plastics, which encourages people to adopt a greener lifestyle.

She also appealed to the public to exercise social distancing while enjoying the countryside amid the epidemic.

Tenants of the EcoPark, country park refreshment kiosks and the Hong Kong Wetland Park will benefit from increased rental concessions for government premises.

To help tenants cope with the economic impact of the COVID-19 epidemic, rental concessions of government premises from April to September will be increased from 50% to 75%.

The Environment Bureau said tenants of the EcoPark, country park refreshment kiosks and the Hong Kong Wetland Park will receive additional rental concessions of about $3.6 million.

Together with the 50% rental concessions provided by the Government from last October to March, these tenants will receive concessions of more than $17 million within 12 months, the bureau said.

Meanwhile, tenants of the Hong Kong Wetland Park will receive a full rental waiver during the park’s closure.

Carlos Gustavo T. Moreira, Maria José Pacifico and Sergio Romaña Ibarra
Bull. Amer. Math. Soc. 57 (2018), 269-292.
Abstract, references and article information

(Wiley) Heart failure and cancer are conditions with a number of shared characteristics. A new study published in the Journal of Internal Medicine found that in patients with heart failure, several known tumor markers can also be indicators of heart failure severity and progression.

(American Marketing Association) Nonprofits may better meet their missions by learning to effectively employ the entirety of the marketing mix to attract individuals to available donation opportunities.

(University of Massachusetts Amherst) As physicians and families know too well, though Alzheimer's disease has been intensely studied for decades, too much is still not known about molecular processes in the brain that cause it. Now researchers at the University of Massachusetts Amherst say new insights from analytic theory and molecular simulation techniques offer a better understanding of amyloid fibril growth and brain pathology.

(Goethe University Frankfurt) According to modern particle physics, matter produced when neutron stars merge is so dense that it could exist in a state of dissolved elementary particles. This state of matter, called quark-gluon plasma, might produce a specific signature in gravitational waves. Physicists at Goethe University Frankfurt and the Frankfurt Institute for Advanced Studies have now calculated this process using supercomputers.

(DOE/Lawrence Berkeley National Laboratory) A new study, led by researchers at Berkeley Lab and UC Berkeley, suggests new paths for catching the signals of dark matter particles that have their energy absorbed by atomic nuclei.

Current regulations do not effectively prevent potentially misleading claims, says Imperial scientists

(Stanford School of Engineering) After analyzing 95 million traffic stop records, filed by officers with 21 state patrol agencies and 35 municipal police forces from 2011 to 2018, a Stanford-led research team concluded that 'police stops and search decisions suffer from persistent racial bias.'

3 October 2019

14 January 2020

Research Event

Event participants

Ahmed Tabaqchali, Chief Investment Officer, Asia Frontier Capital Iraq Fund; Adjunct Assistant Professor, American University of Iraq Sulaimani
Moderator: Renad Mansour, Senior Research Fellow, Middle East and North Africa Programme, Chatham House

⁶⁸Ga-DOTATOC-PET/MRI (⁶⁸Gallium-DOTATOC-positron emission tomography/magnetic resonance imaging) combines the advantages of PET in the acquisition of metabolic-functional information with the high soft tissue contrast of MRI. Standardized uptake values (SUV) in tumors were suggested as a measure of somatostatin receptor expression. A challenge with receptor ligands is, that the distribution volume is confined to tissues with tracer-uptake, potentially limiting SUV quantification. In this study, different functional, three-dimensional (3D) SUV, apparent diffusion coefficient (ADC) parameters and arterial tumor enhancement were tested for the characterization of gastroendopancreatic neuroendocrine tumors (GEP-NET). Methods: For this single-center, cross-sectional study, 22 patients with 24 histologically confirmed GEP-NET lesions (15 men/7 women; median, 61 years, range, 43-81 years), who received hybrid ⁶⁸Ga-DOTA-PET/MRI examinations at 3T between January 2017 and July 2019 met eligibility criteria. SUVs, tumor-to-background ratios (TBR), the total functional tumor volume (TFTV), ADCmean and ADCmin were measured based on volumes of interest (VOI) and examined with receiver operating characteristic analysis to determine cut-off values for differentiation between low and intermediate grade GEP-NET. Spearman’s rank correlation coefficients were used to assess correlations between functional imaging parameters. Results: The ratio of PET-derived SUVmean and diffusion-weighted imaging (DWI)-derived ADCmin was introduced as a combined variable to predict tumor grade, outperforming single predictors. Based on a threshold ratio of 0.03 to be exceeded, tumors could be classified as grade 2 with a sensitivity of 86% and specificity of 100%. SUV and functional ADC values as well as arterial contrast enhancement parameters showed non-significant and mostly negligible correlations. Conclusion: As receptor density and tumor cellularity appear to be independent, potentially complementary phenomena, the combined PET/MRI ratio SUVmean/ADCmin may be used as a novel biomarker, allowing to differentiate between grade 1 and 2 GEP-NET.

Objective: To develop a novel approach to generate individual maps of white matter (WM) innate immune cell activation using ¹⁸F-DPA-714 translocator protein (TSPO) positron emission tomography (PET), and to explore the relationship between these maps and individual trajectories of disability worsening in patients with multiple sclerosis (MS). Methods: Patients with MS (n = 37), whose trajectories of disability worsening over the 2 years preceding study entry were calculated, and healthy controls (n = 19) underwent magnetic resonance magnetic and ¹⁸F-DPA-714 PET. A threshold of significant activation of ¹⁸F-DPA-714 binding was calculated with a voxel-wise randomized permutation-based comparison between patients and controls, and used to classify each WM voxel in patients as characterized by a significant activation of innate immune cells (DPA+) or not. Individual maps of innate immune cell activation in the WM were employed to calculate the extent of activation in WM regions-of-interests and to classify each WM lesion as "DPA-active", "DPA-inactive" or "unclassified". Results: Compared with the WM of healthy controls, patients with MS had a significantly higher percentage of DPA+ voxels in the normal-appearing WM, (NAWM in patients=24.9±9.7%; WM in controls=14.0±7.8%, p<0.001). In patients with MS, the percentage of DPA+ voxels showed a significant increase from NAWM, to perilesional areas, T2 hyperintense lesions and T1 hypointense lesions (38.1±13.5%, 45.0±17.9%, and 51.9±22.9%, respectively, p<0.001). Among the 1379 T2 lesions identified, 512 were defined as DPA-active and 258 as DPA-inactive. A higher number of lesions classified as DPA-active (OR=1.13, P = 0.009), a higher percentage of DPA+ voxels in the NAWM (OR=1.16, P = 0.009) and in T1-spin-echo lesions (OR=1.06, P = 0.036), were significantly associated with a retrospective more severe clinical trajectory in patients with MS. Conclusion: A more severe trajectory of disability worsening in MS is associated with an innate immune cells activation inside and around WM lesions. ¹⁸F-DPA-714 PET may provide a promising biomarker to identify patients at risk of severe clinical trajectory.

Prostate specific membrane antigen (PSMA) targeting Positron Emission Tomography (PET) imaging is becoming the reference standard for prostate cancer (PC) staging, especially in advanced disease. Yet, the implications of PSMA-PET derived whole-body tumor volume for overall survival are poorly elucidated to date. This might be due to the fact that (semi-) automated quantification of whole-body tumor volume as PSMA-PET biomarker is an unmet clinical challenge. Therefore, a novel semi-automated software is proposed and evaluated by the present study, which enables the semi-automated quantification of PSMA-PET biomarkers such as whole-body tumor volume. Methods: The proposed quantification is implemented as a research prototype (MI Whole Body Analysis Suite, v1.0, Siemens Medical Solutions USA, Inc., Knoxville, TN). PSMA accumulating foci were automatically segmented by a percental threshold (50% of local SUV_max). Neural networks were trained to segment organs in PET-CT acquisitions (training CTs: 8,632, validation CTs: 53). Thereby, PSMA foci within organs of physiologic PSMA uptake were semi-automatically excluded from the analysis. Pretherapeutic PSMA-PET-CTs of 40 consecutive patients treated with ¹⁷⁷Lu-PSMA-617 therapy were evaluated in this analysis. The volumetric whole-body tumor volume (PSMATV50), SUV_max, SUVmean and other whole-body imaging biomarkers were calculated for each patient. Semi-automatically derived results were compared with manual readings in a sub-cohort (by one nuclear medicine physician using syngo.MM Oncology software, Siemens Healthineers, Knoxville, TN). Additionally, an inter-observer evaluation of the semi-automated approach was performed in a sub-cohort (by two nuclear medicine physicians). Results: Manually and semi automatically derived PSMA metrics were highly correlated (PSMATV50: R2=1.000; p<0.001; SUV_max: R2=0.988; p<0.001). The inter-observer agreement of the semi-automated workflow was also high (PSMATV50: R2=1.000; p<0.001; ICC=1.000; SUV_max: R2=0.988; p<0.001; ICC=0.997). PSMATV50 [ml] was a significant predictor of overall survival (HR: 1.004; 95%CI: 1.001-1.006, P = 0.002) and remained so in a multivariate regression including other biomarkers (HR: 1.004; 95%CI: 1.001-1.006 P = 0.004). Conclusion: PSMATV50 is a promising PSMA-PET biomarker that is reproducible and easily quantified by the proposed semi-automated software. Moreover, PSMATV50 is a significant predictor of overall survival in patients with advanced prostate cancer that receive ¹⁷⁷Lu-PSMA-617 therapy.

The use of protein biomarkers as surrogates for clinical endpoints requires extensive multilevel validation including development of robust and sensitive assays for precise measurement of protein concentration. Multiple reaction monitoring (MRM) is a well-established mass-spectrometric method that can be used for reproducible protein-concentration measurements in biological specimens collected via microsampling. The dried blood spot (DBS) microsampling technique can be performed non-invasively without the expertise of a phlebotomist, and can enhance analyte stability which facilitate the application of this technique in retrospective studies while providing lower storage and shipping costs, because cold-chain logistics can be eliminated. Thus, precise, sensitive, and multiplexed methods for measuring protein concentrations in DBSs can be used for de novo biomarker discovery and for biomarker quantification or verification experiments. To achieve this goal, MRM assays were developed for multiplexed concentration measurement of proteins in DBSs.

The lower limit of quantification (LLOQ) was found to have a median total coefficient of variation (CV) of 18% for 245 proteins, whereas the median LLOQ was 5 fmol of peptide injected on column, and the median inter-day CV over 4 days for measuring endogenous protein concentration was 8%. The majority (88%) of the assays displayed parallelism, whereas the peptide standards remained stable throughout the assay workflow and after exposure to multiple freeze-thaw cycles. For 190 proteins, the measured protein concentrations remained stable in DBS stored at ambient laboratory temperature for up to 2 months. Finally, the developed assays were used to measure the concentration ranges for 200 proteins in twenty same sex, same race and age matched individuals.

Mass spectrometry (MS) and proteomics offer comprehensive characterization and identification of microorganisms and discovery of protein biomarkers that are applicable for diagnostics of infectious diseases. The use of biomarkers for diagnostics is widely applied in the clinic and the use of peptide biomarkers is increasingly being investigated for applications in the clinical laboratory. Respiratory-tract infections are a predominant cause for medical treatment, although, clinical assessments and standard clinical laboratory protocols are time-consuming and often inadequate for reliable diagnoses. Novel methods, preferably applied directly to clinical samples, excluding cultivation steps, are needed to improve diagnostics of infectious diseases, provide adequate treatment and reduce the use of antibiotics and associated development of antibiotic resistance. This study applied nano-liquid chromatography (LC) coupled with tandem MS, with a bioinformatics pipeline and an in-house database of curated high-quality reference genome sequences to identify species-unique peptides as potential biomarkers for four bacterial pathogens commonly found in respiratory tract infections (RTIs): Staphylococcus aureus; Moraxella catarrhalis; Haemophilus influenzae and Streptococcus pneumoniae. The species-unique peptides were initially identified in pure cultures of bacterial reference strains, reflecting the genomic variation in the four species and, furthermore, in clinical respiratory tract samples, without prior cultivation, elucidating proteins expressed in clinical conditions of infection. For each of the four bacterial pathogens, the peptide biomarker candidates most predominantly found in clinical samples, are presented. Data are available via ProteomeXchange with identifier PXD014522. As proof-of-principle, the most promising species-unique peptides were applied in targeted tandem MS-analyses of clinical samples and their relevance for identifications of the pathogens, i.e. proteotyping, was validated, thus demonstrating their potential as peptide biomarker candidates for diagnostics of infectious diseases.

Lung cancer (LC) remains the leading cause of mortality from malignant tumors worldwide. In our previous study, we surveyed both IgG and IgM-bound serological biomarkers and validated a panel of IgG-bound autoantigens for early LC diagnosis with 50% sensitivity at 90% specificity. To further improve the performance of these serological biomarkers, we surveyed HuProt arrays, comprised of 20,240 human proteins, for IgA-bound autoantigens because IgAs are a major immunoglobulin isotype in the lung. Integrating with IgG-bound autoantigens, we discovered and validated a combined biomarker panel using ELISA-format tests. Specifically, in Phase I, we obtained IgA-based autoimmune profiles of 69 early stage LC patients, 30 healthy subjects and 25 patients with lung benign lesions (LBL) on HuProt arrays and identified 28 proteins as candidate autoantigens that were significantly associated with early stage LC. In Phase II, we re-purified the autoantigens and converted them into an ELISA-format testing to profile an additional large cohort, comprised of 136 early stage LC patients, 58 healthy individuals, and 29 LBL patients. Integration of IgG autoimmune profiles allowed us to identify and validate a biomarker panel of three IgA autoantigens (i.e. BCL7A, and TRIM33 and MTERF4) and three IgG autoantigens (i.e. CTAG1A, DDX4 and MAGEC2) for diagnosis of early stage LC with 73.5% sensitivity at >85% specificity. In Phase III, the performance of this biomarker panel was confirmed with an independent cohort, comprised of 88 early stage LC patients, 18 LBL patients, and 36 healthy subjects. Finally, a blind test on 178 serum samples was conducted to confirm the performance of the biomarker panel. In summary, this study demonstrates for the first time that an integrated panel of IgA/IgG autoantigens can serve as valuable biomarkers to further improve the performance of early diagnosis of LC.

Invitation Only Research Event

Event participants

Professor Robert Shiller, Sterling Professor of Economics, Yale University
Chair: Marianne Schneider-Petsinger, Research Fellow, US and the Americas Programme Chatham House

8 October 2019

Sandi M. Azab
Mar 31, 2020; 0:jlr.D120000630v1-jlr.D120000630
Methods