Memories of My Childhood

"I think there was never a child in the history of Washington or Oregon who ever had so sad a story to write as I, Anna Griswold. My father was shot but lived to gain the block house, where he sank his head in my arms and died. I well remember the three days' siege in the blockhouse, without food or water; my mother and I on either side of our dead, and the cannon booming over our heads.

Memories of My Childhood

"I think there was never a child in the history of Washington or Oregon who ever had so sad a story to write as I, Anna Griswold. My father was shot but lived to gain the block house, where he sank his head in my arms and died. I well remember the three days' siege in the blockhouse, without food or water; my mother and I on either side of our dead, and the cannon booming over our heads.

Development of the Baltic Armed Forces in Light of Multinational Deployments

View the Executive SummaryDeveloping coalition security strategies within NATO has never been easy. However, it does help to have a thorough understanding of one’s allies and their concerns and perspectives. This monograph provides an in-depth view of how three Baltic nations (Estonia, Latvia, and Lithuania) view current and future security threats and likely problems. It also recommends some ways in which the United States might respond to these issues.https://press.armywarcollege.edu/monographs/1520/thumbnail.jp

Training Indigenous Forces in Counterinsurgency: A Tale of Two Insurgencies

The author examines the British experience in building and training indigenous police and military forces during the Malaya and Cyprus insurgencies. These two insurgencies provide a dramatic contrast to the issue of training local security forces. In Malaya, the British developed a very successful strategy for training the Malayan Police and army. In Cyprus, the British strategy for building and training local security forces generally was ineffective. The author argues that some important lessons can be drawn from these case studies that are directly applicable to current U.S. counterinsurgency doctrine.https://press.armywarcollege.edu/monographs/1719/thumbnail.jp

The Security Concerns of the Baltic States as NATO Allies

View the Executive SummaryIf the United States is likely to fight in a coalition with small allies in the future, then it is useful to understand the experience, capabilities, and perspectives of those allies. Since regaining independence in 1991, the countries of Latvia, Estonia, and Lithuania have been very active in supporting NATO and U.S. military operations abroad. It is notable that the three Baltic countries have also used the deployment of a significant part of their forces in the last decade as a major part of their program to carry out a major force transformation.https://press.armywarcollege.edu/monographs/1318/thumbnail.jp

Effects of bcrp and p-gp modulators on the penetration of aflatoxin b1 into the mouse brain

This study was conducted to determine whether the plasma and brain concentrations of AFB1 are affected by the modulation of P-gp and BCRP using zosuquidar (ZQR) and prazosin (PRZ), respectively. In this study, a total of 40 healthy adult male BALB/c mice (32±3.7 g) were used. The animals were randomly divided into 5 groups, with 8 animals per group. Group 1 was used for method validation. Group 2 (AF) received intraperitoneal AFB1 at a dose of 20 mg/kg of body weight. Groups 3 (AF+PRZ), 4 (AF+ZQR), and 5 (AF+PRZ+ZQR) received 20 mg/kg of AFB1 intraperitoneally 30 min after the intraperitoneal administration of prazosin (0.3 mg/kg), zosuquidar (25 mg/kg), and prazosin+zosuquidar (0.3 mg/kg prazosin + 25 mg/kg zosuquidar), respectively. Six hours after the administration of AFB1, blood and brain samples were collected from the animals in Groups 2 to 5. AFB1 concentrations were determined using an HPLC system with fluorescence detection. Individual and simultaneous administration of prazosin and zosuquidar significantly reduced the brain concentrations of AFB1 in comparison to a single administration of AFB1 (P<0.05). The brain/plasma ratio of the AF group was higher than that of the other groups (AF+PRZ, AF+ZQR, and AF+PRZ+ZQR) (P<0.05). Inducers of transmembrane proteins, especially BCRP, can be life saving during acute AFB1 poisoning

Isotropy of the velocity of light and the Sagnac effect

In this paper, it is shown, using a geometrical approach, the isotropy of the velocity of light measured in a rotating frame in Minkowski space-time, and it is verified that this result is compatible with the Sagnac effect. Furthermore, we find that this problem can be reduced to the solution of geodesic triangles in a Minkowskian cylinder. A relationship between the problems established on the cylinder and on the Minkowskian plane is obtained through a local isometry.Comment: LaTeX, 13 pages, 3 eps figures; typos corrected, added references, minor changes; to appear in "Relativity in Rotating Frames", ed. G. Rizzi G. and M.L. Ruggiero, Kluwer Academic Publishers, Dordrecht (2003

LUMINOS-102: Lerapolturev with and without α-PD- 1 in unresectable α-PD- 1 refractory melanoma

Lerapolturev (lera, formerly PVSRIPO) is a novel poliovirus based intratumoral immunotherapy that infects both cancer cells and antigen-presenting cells (APCs) via CD155, the poliovirus receptor. Lera has direct anticancer effects while also generating type I/III interferon-dominated inflammation and anti-tumor T-cell priming and activation via infection of local APCs. LUMINOS-102 (NCT04577807) is a multi-center, open-label, two-arm randomized Phase 2 study investigating the efficacy and safety of lera ± α-PD- 1 in patients with unresectable melanoma who failed prior α-PD- 1 therapy. Cross-over to the α-PD- 1 arm is permitted after progression, PR for ≥6 mo or 6 mo on treatment with SD. The maximum initial lera dose was 6x108 TCID50 /visit every 3 or 4 weeks (Q3/4 W). As of March 2022, the maximum lera dose was increased to 1.6 x 109 TCID50/visit, every week (QW) for 7 weeks (induction), followed by Q3/4 W dosing (maintenance). As of 20-Jun- 2022, 21 participants (10 male, 11 female, median 64 yrs) received lera (n = 14 at initial dose, Q3/4 W; n = 4 at increased dose, Q3/4 W; n = 3 at increased dose, QW) ± αPD-1. Five patients are currently on treatment. With the initial regimen, no objective responses and a CBR of 7% were observed. However, with the higher dose regimen, 1 complete response and a CBR of 71% (5/7) has been observed. Two of 4 participants with stable disease have evidence of response (1 with resolution of uninjected lung metastasis, 1 with decreased PET signal in injected and uninjected lesions receiving combination therapy). The only treatment related AE in \u3e1 pt was fatigue (19%, all grade 1 or 2). No dose-limiting toxicities or treatment-related SAEs were reported. Multiplex-IF analysis of on-treatment tumor biopsies will be presented. Lera ± αPD-1 is well tolerated, with early signs of efficacy at the higher dose level. Enrollment and randomization are ongoing

A randomized phase 2 study of trastuzumab and pertuzumab (TP) compared to cetuximab and irinotecan (CETIRI) in advanced/metastatic colorectal cancer (mCRC) with HER2 amplification: SWOG S1613

Background: HER2 (ERBB2) over-expression and amplification (HER2+) is seen in a small but distinct subset (2-3%) of mCRC and is enriched in RAS/BRAF wild type (WT) tumors. This subset is characterized by a limited response to anti-epidermal growth factor receptor monoclonal antibodybased (anti-EGFR) therapy and a promising response to dual-HER2 inhibition. Methods: In this multicenter, open label, randomized, phase 2 trial, we enrolled 54 patients with RAS/BRAF WT HER2+ mCRC who had had disease progression after 1 or 2 previous therapies. HER2 status was confirmed centrally with immunohistochemistry (IHC) and in-situ hybridization (ISH). HER2+ was defined as IHC 3+ or 2+ and ISH amplified (dual-probe HER2/CEP17 ratio \u3e 2.0). Patients were then randomly assigned in a 1:1 ratio to receive either TP (trastuzumab [loading 8 mg/kg then 6 mg/kg] + pertuzumab [loading 840 mg then 420 mg] every 3 weeks) or CETIRI (cetuximab 500 mg/m2 + irinotecan 180 mg/m2 every 2 weeks). Crossover was allowed for patients on CETIRI arm to TP (cTP) after progression. Restaging (per RECIST v1.1) was performed at 6 and 12 weeks and then every 8 weeks until progression. The primary endpoint was progression-free survival (PFS). Key secondary endpoints were overall response rate (ORR), overall survival (OS) and safety. Results: A total of 54 (out of planned 62 due to low accrual) patients were randomized to TP (26) and CETIRI (28) between 10/2017 and 12/2021. By 8/18/2022, 20 patients had crossed over to cTP arm. One CETIRI patient was not analyzable. The results for key endpoints by protocol defined stratification factors, prior irinotecan (Piri) (yes or no) and HER2/CEP17 ratio (HCR) (\u3e5 or ≤5), are summarized as of data cut-off of 9/6/2022. PFS did not vary significantly by treatment: medians 4.4 (95%CI: 1.9 - 7.6) months in TP group and 3.7 (95%CI: 1.6 - 6.7) months in CETIRI group (p = 0.35). Grade≥3 adverse events occurred in 23%, 46% and 40% of patients in TP, CETIRI and cTP groups. Conclusions: Dual-HER2 inhibition with TP appears to be a safe and effective treatment option for patients with RAS/BRAF WT HER2+ mCRC with a promising response rate of31%.Higher level of HER2 amplification may provide a greater degree of clinical benefit from TP compared to CETIRI. Future correlative efforts will explore biomarkers of response/resistance with this strategy

A ‘Baby GDA’: Norwich’s Airspace during the Second World War

Throughout the Second World War, the Luftwaffe attacked Norwich on various occasions. The impact this had on the city was recorded visually on the ‘Norwich Bomb Map’. This cartographic depiction, however, only records a single ‘horizontal’ component of the aerial ‘battlescape’. In reality, the aerial battlefield comprised a combination of Norwich’s air defences and the flightpaths of the Luftwaffe bombers, which existed in three-dimensional space. As other scholars have developed methodologies for reconstructing anti-aircraft ‘fire domes’, this article will combine these concepts with a new approach that reconstructs historic flightpaths to give a three-dimensional overview of Norwich’s ‘Gun Defended Area’. By examining all components of Norwich’s airspace, this article will demonstrate the importance of considering the vertical component of a battlescape